Referred pain is the perception of pain at a site that is different from the origin of the painful stimulus. Its origin is in visceral organs and it is projected to different areas of the body surface and somatic tissues. The origin of the referred pain is presently thought to depend on the organization of neural circuits that process somatic and visceral pain. In general, it is thought that there is somatovisceral integration at peripheral, spinal and supraspinal levels. A number of recent studies have demonstrated unit responses of dorsal horn neurons to both visceral and somatic afferents. Spinal lamina I neurons have been demonstrated as an essential early element in the processing of nociceptive input. They receive afferences from the skin, joints, muscles and the viscera that project to the brainstem, thalamus and other components of the pain matrix. It has been demonstrated that both A-delta (thinly myelinated 1-4μ) and C-fibers (unmyelinated) from multiple dorsal roots can synapse directly on lamina 1 neurons giving them an anatomical basis to act as an integrator of multimodal sensory inputs. It has also been well established that somatic or nerve injury produces a much wider nociceptive afferent input than the stimulated dermatome. Lissauer’s tract (dorsolateral spinal cord) distributes the nociceptive input from dorsal root ganglion afferents at least two segments above and below the activated spinal cord segment. Synapses on nociceptive dorsal horn (DH) lamina I pain projecting neurons may be homosynaptic or heterosynaptic and are subject to maladaptive neuroplasticity (central sensitization) that increases their excitability and response to different modalities of stimulation (A-beta afferences).
Recent experimental evidence derived from an in vitro intercostal T9 and greater splanchnic peripheral nerve preparation demonstrates that there is somatic and visceral thin-fiber (A delta and C-fiber) convergence onto a subset of lamina 1 neurons some of which are pain projecting and others are local circuit neurons. Synaptic input from both the somatic and visceral neurons is suprathreshold and evokes depolarization in a subset of pain projecting neurons. Thus these lamina I neurons are the first site in the CNS of somaticvisceral convergence. Approximately 25% of the recorded lamina I neurons receive somatic and visceral inputs from converging monosynaptic C-fibers. The neurons are both pain projecting and local circuit. Lamina I neurons were also excited by either somatic or visceral afferents which is evidence for modality-specific pathways to the dorsal horn. As noted above, maladaptive neuroplasticity may occur in subthreshold stimulated pain projecting neurons (modality-specific sensitization) or in excitatory inter-neurons that mediate polysynaptic pathways. This may alter the processing of input in those neurons that receive converging input and determine the outcome of the somatovisceral integration. Other research has demonstrated that stimulation of intercostal afferents can inhibit the discharge of thoracic spinal neurons that are excited by noxious stimulation of visceral afferent nerves. Some lamina I neurons receive supra or subthreshold excitatory visceral projections as well as inhibitory somatic input that is the anatomical basis of this phenomenon. This may also be a mechanism to modulate visceral nociceptive activity in lamina I cells with somatovisceral convergence. In general, it requires strong somatic A-delta and C-fiber inhibition of lamina I convergent neurons to inhibit visceral pain.
The anatomy and physiologic function of lamina I neurons that receive inhibitory afferences from both somatic and visceral nerves is extremely complex. Inhibitory input occurs primarily in local circuit neurons that demonstrate a rhythmic pattern of intrinsic firing. A subset of these neurons is local circuit GABA-ergic neurons whose axons are immunoreactive for vesicular GABA transporter and project densely within lamina I and II. Inhibition of these cells would disinhibit their postsynaptic projections (double-disinhibition) that in turn would amplify excitation of pain projecting neurons. Some lamina I local circuit neurons are excitatory interneurons that directly target pain projecting neurons. Thus local circuit modulation of Aδ and C-fiber input from somatic or visceral afferents influences the physiologic activity of pain projecting neurons. This mechanism may be similar to the reciprocal inhibition demonstrated in somatic and visceral AΒ and Aδ afferent input to wide-dynamic neurons in both cat and monkey.
Present evidence supports the hypothesis that the neural substrate of referred pain is modulation of the somatic and visceral inputs to lamina I pain projecting neurons that receive converging somatic and visceral input.
1.Angina pectoris:
a.Pain is often described as pressure, tightness, or heaviness in the substernal left chest wall and left upper arm (T2). Overwhelmingly does not radiate to the fingers
b.Radiations to the neck, jaw, shoulders, back or one or both arms
c.Associated indigestion or heart burn with nausea or vomiting
d.Most often exercise (but not always) related
2.Pleuritic pain radiations:
a.Lancinating pain over the affected area of involved pleura
b.Referred pain to the shoulder and back that is exacerbated by inspiration and expiration or cough
c.Mechanical hyperalgesia or allodynia over the affected area of the chest wall
3.Gall bladder pain radiation:
a.Severe colicky right upper abdominal pain
b.Radiation to the interscapular areas, right scapula (sometimes to the tip at the T6 level) and shoulder
c.Associated anorexia, nausea and vomiting
4.Liver disease pain radiations:
a.Usually the pain is most severe in the right upper quadrant below the right costal margin
b.Radiates to the back and right shoulder (less frequently)
5.Pancreatic pain radiations:
a.Severe upper abdominal pain associated with nausea and vomiting; pain may be in the epigastrium
b.Radiation is straight through to the back at times slightly relieved by sitting up and leaning forward with the knees flexed
c.Less frequent radiations are to the chest, periumbilical area, back, lower abdomen and flanks
6.Spleen pain radiations:
a.Pain discomfort or a feeling of fullness or heaviness in the upper left abdominal quadrant
b.Pain radiation to the left shoulder and infrequently the back
7.Esophageal pain radiations
a.Retrosternal chest pain that may radiate to the back
8.Stomach pain radiations:
a.GERD radiates substernally
b.Pain radiations are to the back particularly with posterior penetrating ulcers
After CNS lesions pain may be perceived in a specific body region or become widespread. In general, it is constant and moderate to severe in intensity. It is exacerbated by mechanical and thermal stimuli (most often cold) and emotional upset. Its quality is usually burning, although various dysesthetic sensations, “pins and needles”, ache, and deep pressure are common. There may be spontaneous episodes of lancinating pain or sharp excruciating unrelenting pain. Patients frequently have decreased mechanical sensitivity in the areas affected by pain. The burning sensation and loss of mechanical sensitivity are usually most severe distally. During exacerbations, there may be associated vomiting, tachycardia, hypertension, and hyperventilation.
A major mechanism underlying central pain is central sensitization. Early studies demonstrated that nociceptive afferent activity from a peripheral injury could trigger a long lasting increased excitability of spinal cord neurons, an alteration of the usual stimulus-response relationship. In essence a change in the gain of the somatosensory system. Woolf and colleagues demonstrated that a 10-20 second low frequency (1-10 Hz) electrical or natural activation of peripheral nociceptors increased synaptic transmission (efficacy) in dorsal horn spinal cord neurons that lasted for minutes after cessation of the conditioning stimulus. This phenomenon differs from windup that causes a progressive neuronal discharge during continual identical stimuli (homosynaptic potentiation). Central sensitization induces facilitation after the conditioning stimulus that can be autonomous or requires a low level of nociceptive afference to maintain it. Central sensitization also produces heterosynaptic potentiation. In this situation, one type of nociceptor sensory fibers that are stimulated amplifies the response of other non-stimulated non-nociceptor or nociceptor fibers.
An underlying tenet of central sensitization is that in most central circuits, the receptive fields of dorsal horn neurons are only partially determined by the firing of an action potential. Most synaptic input to neurons is subthreshold; either not sufficient to depolarize the target neuron or the membrane excitability of the neuron is decreased by tonic inhibition. Normally subthreshold synaptic inputs can be amplified by:
1.A presynaptic increase in neurotransmitter release
2.Increased responsiveness of the postsynaptic membrane
3.Or decreased inhibition
These mechanisms raise subthreshold synaptic input sufficiently to produce action potentials and thus alter the functional properties of the target neuron. Central sensitization is also maintained by:
1.Activation of microglia (release cytokines, chemokines and neurotransmitters)
2.Astrocytes (more important in maintenance than induction)
3.Gap junctions
4.Membrane excitability
5.Gene transcription
The clinical features of central sensitization include:
1.Pain hypersensitivity
2.Dynamic tactile allodynia
3.Secondary punctate or pressure hyperalgesia
4.After sensations (the pain is not stimulus bound)
5.Enhanced temporal summation (“wind up”)
On a molecular level, central sensitization is similar to activity-dependent synaptic plasticity. This is a complex process that involves synaptic modulation and excitatory amino acids, alterations in the kinetics and physiology of ion channels, increased synaptic density of ionotropic receptors and activation of pre and post synaptic threonine and serine kinases. These processes lead to increased calcium influx through NMDA receptors that induce multiple intracellular enzymatic cascades that increase neuronal membrane excitability and induce gene transcription that in turn increases synaptic strength (efficacy). These changes enable subthreshold nociceptive inputs to depolarize nociceptive neurons, reduce their threshold to fire, expand the size of their receptive fields, and enhance their responsiveness. A significant aspect of the process is that low threshold afferents (AΒ fibers) are able to depolarize nociceptive neurons and that afferences outside of the injury site can elicit pain.
Neuropathic pain is caused by lesions of the somatosensory nervous system that alter its anatomy and function. It manifests spontaneously and responses to both noxious and innocuous stimuli are pathologically amplified. It is a consequence of maladaptive neuroplasticity of the nociceptive system at many levels. Its underlying mechanisms include:
1.Ectopic generation of action potentials
2.Facilitation and disinhibition of synaptic transmission
3.Disrupted synaptic connectivity
4.Formation of new synaptic circuits
5.Neuroimmune activation of microglia and astrocytes
Genetic predisposition and polymorphisms, age, gender are important factors that determine risk of developing neuropathic pain. The pain is maladaptive as it does not alert the individual to a tissue destructive stimulus or participate in repair.
The following are central neuropathic pain disorders that affect the axial skeleton.
1.The disease affects approximately 8% of all stroke patients: there are approximately 700,0000 new and recurrent strokes per year in the USA which would cause 56,000 patients with CPSP
2.It is a particularly devastating condition that is frequently refractory to medical, surgical and deep brain stimulation modalities of treatment
3.CPSP is a persisting neuropathic pain of central origin that cannot be attributed to peripheral, nociceptive, or inflammatory processes.
4.Possible criteria for post stroke pain:
a.A clear cerebrovascular accident
b.The onset of pain at some point after the stroke
c.Alteration primarily of the spinothalamic pathways
1.CPSP I is primarily associated with spinothalamic tract disruption irrespective of stroke type
2.Thalamic pain:
a.The P1 component of the posterior cerebral artery may be infarcted or ischemic lesions of the thalamogeniculate and less frequently, the thalamoperforate arteries are involved.
b.Thalamic hemorrhage in the ventrobasilar complex is well described
c.Pain on the contralateral side of the body may be in a hemisensory pattern or primarily affect the extremities, face or axillary body surface
d.Most CPSP patients present within one to six months of the stroke. However, some patients develop the pain from 1 to 6 years after the ictus
e.There is loss of thermal sensibility that accompanies and may precede the onset of pain. There may be distorted cold or heat sensations as well as paradoxical reactions to painful stimuli
f.Allodynia to cold or dysesthesia to cold is not infrequent
g.Allodynia to mechanical stimuli is seen in approximately 75% of patients
h.Pain is usually confined to regions of altered pinprick sensation. Painful areas may be smaller than the borders of sensory dysfunction
i.Some studies have demonstrated that cold hypoesthesia may be associated with burning cold continuous pain but may not have associated cold allodynia
j.Normal tactile mechanical sensibility may be associated with tactile allodynia
k.The quality of pain varies. It may be:
i.Continuous or paroxysmal
ii.Lancinating
iii.Cramping
iv.Grueling
v.Burning
l.The predominant pain may be continuous or evokes
m.Evoked pains:
i.Are brief and last only for the duration of the stimulus
ii.Rarely, they are not stimulus bound and can last for minutes to hours (after sensations). Extremely rare after sensations last for days.
n.Evoked and spontaneous pains may be predominant in deep tissue
o.Movement induced allodynia and pain may be seen in approximately 20 % of patients
p.The most consistent abnormality is abnormal temperature and pain sensitivity but all patients have some loss of somatic sensory modalities (may be difficult to discern)
1.Thalamic pain may be seen following ischemic infarction from thrombosis or emboli to the P1 area of the posterior cerebral artery, the thalamogeniculate or thalamoperforate arteries
2.Hemorrhage into the ventrobasilar complex
3.Lesions within the ventrocaudal nuclei of the thalamus, particularly the ventroposterior inferior nucleus are most commonly associated with CPSP
4.The pathogenesis of CPSP is incompletely understood. Possible mechanisms include:
a.Hyperexcitability of thalamic pain projecting neurons following disruption of ascending spinothalamic pathways:
i.Release of inhibition from a lesion of lemniscal pathways or the spinothalamic pathway
ii.Release of inhibition due to degeneration of corticothalamic neurons that project to the reticular nucleus that activate GABAergic inhibitory neurons that regulate the excitability of somatosensory relay thalamic nuclei
iii.Loss of normal cold inhibition from lamina I projecting neurons to the insula cortex and thalamus. The lateral cool projecting (spinothalamic system) normally inhibits the medical system whose origins are heat-pinch-cold neurons. These neurons project from lamina I to the medical thalamus. A lesion of the lateral spinothalamic system disinhibits this system that causes cold allodynia, burning continuous pain from disruption of thermal modality integration inhibition of nociceptive neurons. An alternate view is that cold fiber projections drive pain-projecting neurons in the thalamus.
iv.The ventroposterior medial intralaminar and reticular nuclei are essential components of post stroke pain. It has been posited that an imbalance between spinothalamic and reticulothalamic pathways may be a component of post stroke pain.
1.MRI to delineate structural involvement of thalamic nuclei
2.MRA to evaluate the vertebral, posterior cerebral, thalamogeniculate and thalamoperforate arteries
3.CT to evaluate the location and volume of thalamic hemorrhage
1.The incidence of pain has been reported in one series to be as high as 25% which is higher than in most series
2.The incidence of chronic post stroke pain (CPSP) has been estimated to be approximately 17% with vascular lesions of the ventroposterolateral complex in the thalamus
1.Burning spontaneous dysesthetic pain which may appear prominently in the chest as the sensory loss abates
2.Mechanical and static allodynia can be evoked in painful areas
3.Abnormalities of thermal sensation and hyperalgesia similar to those seen with thalamic lesions
1.Thrombosis of the vertebral or posterior inferior cerebellar artery that infarcts the spinothalamic tract within the lateral medulla
1.Neurophysiologic studies:
a.Hyperexcitability of thalamic pain projecting neurons with burst firing
2.Central pain mechanisms:
a.Increased regional cerebral blood flow in the thalamus with both Wallenberg and CPSP of cortical origin
1.MRI to delineate the structural damage in the lateral medulla
2.MRA to evaluate the vertebral and PICA arteries
1.Due to the large variation in culture, motor vehicles, social situations and accidents prevalence and incidence of spinal cord injury is difficult to obtain
2.The global incidence of SCI has been estimated to be 23 patients per one million persons (2007). True incidence is dependent on regional factors. In the USA prevalence has been estimated to be 4187 per million of the population
1.As a general rule:
a.Neuropathic pain above the level of injury may be caused by compressive radiculopathies or complex regional pain syndrome
b.Neuropathic pain at the level of injury may be caused by nerve root compression, involvement of the dorsal horns or syringomyelia
c.Neuropathic pain below the level may be due to the trauma itself or other disorders
2.A prospective study of 90 patients with SCI evaluated at 1, 6 and 12 months revealed:
a.80% of patients reported pain at all interval evaluations
b.Neuropathic pain increased with time
c.Musculoskeletal pain slightly decreased
d.Both neuropathic and musculoskeletal pain were present in 59% of patients concomitantly
e.Other neuropathic pain that was not related to SC1 or visceral pain was seen in 1 to 3% of patients
f.Sensory changes, particularly cold-evoked dysesthesia, predicted the development of neuropathic pain below the level of the injury
g.Neuropathic pain may be localized at or below the level of injury and is manifested by mechanical and thermal allodynia and hyperalgesia in addition to severe at level sensory deficits
h.There is no exacerbation of neuropathic pain with movement
i.The development of central type neuropathic pain that is delayed a long time from the injury may be due to the development of post-traumatic syringomyelia. Concomitantly there may be loss of one to two segments of motor function above the area of injury
j.Pain above the level of the injury may be due to carpal tunnel syndrome or musculoskeletal disorders due to wheelchair use and is usually not due to the SCI
k.The pain fluctuates day to day due to activities and the patient’s affect
l.The pattern of pain develops in approximately 30% of spinal cord injured patient. Its major manifestations are:
i.Delayed development: months to years following injury
ii.Spontaneous and diffuse but may be evoked below the injury level
iii.Burning, aching, lancinating and may be associated with hyperalgesia
iv.The pain fluctuates with emotional state, activity, and infections. It may be triggered by unexpected loud noises or movement
v.Burning pain is associated with complete and incomplete lesions. If lemniscal modalities are spared, patients may suffer mechanical allodynia
vi.Non-painful phantom sensations occur in more than 90% of patients
1.Spinal cord injury causes complex changes to damaged tissue at the molecular level that include alterations of:
a.Sodium ion channels
b.Voltage gated calcium channels
c.Glutamate and GABAergic metabolism
d.Serotonergic, noradrenergic, NMDA and opioid receptor physiology
e.Recent interest has been directed toward the GABAergic system in SC1 neuropathic pain:
i.Normal function of GABAergic systems is dependent on the activity of the cation chloride cotransporters Na+- K+ - Cl- cotransporter 1 (NKCC1)
ii.NKCC1 controls Cl- influx and cotransporter 2 (KCC2) regulates Cl- efflux
iii.Activation of NKCC1 and its regulatory pathway are associated with altered Cl- regulation and chronic pain. The KCC2 cotransporter decreases the concentration of Cl- in a pain projecting neuron. GABA release from an inhibitory interneuron onto the pain projecting neuron under physiologic conditions (higher extracellular chloride equilibrium potential) would hyperpolarize the cell, as the Cl- concentration would increase intracellularly. If the KCC2 cotransporter is nonfunctional (less Cl- efflux) or the NKCC1 transporter is upregulated, the intracellular Cl- concentration is increased which reverses the normal chloride equilibrium potential. GABA opens the Cl- channels with a resulting decrease of the concentration of Cl- within the PPN that decreases its threshold to depolarize. In this instance, GABA would increase excitability of the PPN.
2.WNK1 (with no lysine K) is a serine / threonine kinase (encoded by the WNK gene). WNK, through intermediate kinases phosphorylates the Na-K-Cl-cotransporter 1 (NKCC1) and KCC2 and activates and deactivates the channels thus regulating inhibitory tone in dorsal horn pain projecting neurons. NKCC1 is essential in maintaining ionic homeostasis that is also critical for osmotic and GABAergic homeostasis.
1.MRI:
a.This is the best modality to evaluate parenchymal injury, edema and associated soft tissue and visceral images
b.CT of the spine:
a.This is the most effective imaging modality to evaluate bone pathology after SCI
b.Somatosensory evoked potentials:
1.A method to evaluate physiologic function of ascending spinal pathways
c.Transcranial magnetic stimulation:
1.A method to evaluate spinal cord conduction time and functional connections
1.Complete transverse myelopathy is rare other than with high impact motor vehicle accidents or from falls and military combat
2.Spinal cord lesions that affect the cord transversely are most often incomplete and irregular, the neurologic examination reflecting the localization and extent of the lesion
3.T4-T6 is a spinal cord watershed area and conditions of a vascular nature affect this level. T4 is also frequently the level of involvement with embolic disease (drug abuse as well as autoimmune disease)
4.Acute transverse myelopathy is most often due to trauma, demyelinating disease, lymphoma, metastatic disease or vascular disorders
1.Complete cord transection disrupts all ascending pathways from below the lesion as well as all descending pathways from above the lesion. If acute, there is spinal shock with below level paralysis, complete sensory loss, absent reflexes and bowel and bladder incontinence
2.In complete lesions, particularly from extramedullary lesions, the sensory level may be dropped, many levels below the level of the lesion. High thoracic lesions may cause a sensory level at an upper lumbar level. This finding is due to the somatotopic organization of the spinothalamic tract. The lower spinal segments are represented more superficially and laterally
3.A band-like pain radiation or segmental paresthesias may occur at the level of the lesion
4.Localized vertebral pain, particularly to mechanical stimuli (over the vertebral spinous process) such as percussion occurs with destructive lesions, primarily malignancy or infection
5.Pain more severe with recumbency and relieved to a degree with sitting or standing is suggestive of intraparenchymal spinal lesions. Patients that have to sleep sitting up are very suspicious for intrinsic spinal cord tumor (blockade of venous return that increases spinal cord pressure)
6.In general, thoracic level lesions are characterized by root pain and paresthesias that mimic intercostal neuralgia, paraplegia, sensory loss blow the affected level and dysfunction of bowel, bladder and sexual function
7.Lesions above T5 may also have autonomic dysregulation with postural hypotension
1.The differential diagnosis of transverse myelitis is extremely wide:
a.Acute transverse myelitis:
i.Trauma
ii.Autoimmune disease (particularly multiple sclerosis and neuromyelitis optica)
iii.Malignancy, primarily metastasis and lymphoma
iv.Rarely arterial and venous infarction
2.Chronic transverse myelitis:
a.Autoimmune disorders
b.Metabolic diseases
c.Blood dyscrasias
d.Syphilis
e.B12 deficiency
f.Arachnoid cysts
g.Benign tumors
1.Medical evaluation to delineate the category of disease
1.MRI:
a.A new classification to characterize acute transverse myelitis has been proposed:
i.Segmental with rash
ii.Polio-like
iii.Granulomatous nodular
iv.Longitudinally extensive transverse myelitis
v.Short-segment-ovoid or peripherally located
b.The pattern of spinal cord involvement:
i.Posterior column predominant:
1.B12 deficiency
2.Sjogren’s syndrome
3.Syphilis
ii.Anterior 2/3 of the spinal cord:
1.Anterior spinal artery
iii.Extramedullary:
1.Malignancy
2.Disc disease
3.Cysts
4.Degenerative disease of the vertebrae and discs
iv.Central cord:
1.Syrinx
2.Trauma
3.Primary tumor
v.Brown-Sequard (vertical hemisection):
1.Trauma
2.Radiation treatment
3.Rare autoimmune or vascular disease
4.Syringomyelia
5.Disc
1.This is a functional hemisection of the spinal cord
2.Can be categorized as traumatic or non-traumatic
1.The thoracic spine is most commonly involved (75%); cervical spine (17%) and lumbar spine (8%)
2.Most patients are between 15 to 50 years of age
3.Loss of pain and temperature sensation contralateral to the hemisection:
a.The sensory level is usually “dropped” – one or two segments below the level of the lesion
4.Ipsilateral loss of proprioception and vibration modalities:
a.Tactile sensation may be normal or only minimally affected
5.Ipsilateral weakness below the lesion level due to disruption of the descending corticospinal tract
6.Segmental lower motor neuron and sensory loss at the level of the lesion
1.Traumatic causes are the most common and include:
a.Penetrating injuries (most commonly stab wounds:
i.Gunshot injuries
ii.Blunt trauma
b.Non-traumatic lesions:
i.Arachnoid cyst
ii.X-RT
iii.Syringomyelia
iv.Hematomyelia
v.Herniated disc
vi.Neoplasms
vii.Demyelinating disease
viii.Infective / inflammatory disease
c.Unusual causes:
i.Spinal cord herniation (transdural)
ii.Fibrocartilage embolization
iii.Decompression sickness
1.Medical evaluation for causes of blood dyscrasia (if hematomyelia is present), autoimmune disease or infection
1.MRI:
a.MRI with and without contrast to delineate structural parenchymal lesions
2.CT evaluation of bony structures
1.The central cord syndrome is most commonly seen with hyperextension injury of the neck. Underlying spinal cord degenerative disease such as spondylosis or posterior longitudinal ligament calcification are risk factors in elderly patients
1.Acute central spinal cord injury:
a.Severe hyperextension injury of the neck:
i.Patients may be acutely quadriplegic; the legs most often recover within hours or occasionally within minutes
ii.There is patchy sensory loss below the lesion which may involve the thorax
iii.Bladder dysfunction with urinary retention is frequent
iv.Weakness is most severe in the arms and is predominate distally
2.Chronic central cord syndrome:
a.Syringomyelia:
i.The clinical course is slowly progressive
ii.Syringomyelia is frequently associated with Chiari type I or II or Dandy-Walker malformations or follows spinal cord trauma
iii.The decussating fibers of the spinothalamic tract may be affected initially that cause lack of pain and temperature in a cape-like distribution (cervical syrinx) which frequently involves the upper thorax
iv.The pain and temperature loss is often in a suspended distribution and is most often bilateral
v.There is preservation of tactile, vibratory, and proprioceptive modalities that causes a dissociated sensory loss. If the syrinx is asymmetrical it may involve the cervical thalamic tract and alter vibration sensibility
vi.Anterior horn cells are destroyed at the level of the lesion that causes atrophy, paresis, and areflexia. There may be a Horner’s syndrome from involvement of the ciliospinal center of Budge (C8-T2)
vii.Kyphoscoliosis occurs from destruction of the paraspinal muscle innervating neurons of the ventromedian motor nuclei
viii.Spastic paraparesis below the level of the lesion occurs from corticospinal tract involvement. In cervical syrinxes, the biceps and triceps reflexes are lost in association with hyperactive knee and ankle reflexes. Babinski sign is usually elicitable.
ix.In the somatotopic lamination of the spinothalamic tract, cervical sensation is dorsomedial and sacral modalities are ventrolateral. This produces “sacral sparing” as the cervical fibers are affected initially being closer to the central cord
x.Neuropathic pain may be severe in approximately 50% of patients
xi.Neuropathic arthropathy may be seen, particularly in the shoulder, from denervated joints that suffer repeated minor trauma
1.Chronic central cord syndrome is primarily caused by syringomyelia, hydromyelia, hematomyelia and intramedullary spinal cord tumors
2.Acute central cord syndrome is most often due to severe hyperextension injury of the neck
1.MRI to delineate the structural lesions
2.CT to evaluate bone pathology
1.The intercostal nerves are most often affected or injured during the course of thoracic surgery
1.The pain is usually constant and burning in quality in a specific thoracic dermatome
2.Pain may be lancinating
3.Usually the pain begins at the posterior axillary line and radiates anteriorly into the distribution of the injured nerve; it may radiate from front to back
4.In general patients do not splint
5.Patients may have decreased sensation or mechanical hyperalgesia and allodynia in the distribution of the affected nerve
1.Most often intercostal neuralgia is due to a neuropractic injury during the course of retraction with thoracic surgery
2.The dorsal root ganglion and nerve are frequently involved by Herpes zoster that produces hemorrhagic necrosis of the dorsal root ganglia of thoracic segments
1.Herpes zoster is caused by reactivation of the Varicella zoster virus (VZV)
2.The risk of HZ increases with age. The virus persists asymptomatically in sensory ganglia of the cranial nerves and dorsal root ganglia. It reactivates with a decline in cellular immunity or with immunosuppression
3.The virus travels along the sensory nerves to the skin to cause prodromal pain and then the vesicular rash
4.Possibly one out of three individuals will develop HZ
5.The most common dermatomal involvement is in thoracic dermatomes
1.Classically HZ is unilateral. It does not cross the midline and is localized to one dermatome of a single sensory ganglion. In 20% of patients, adjacent dermatomes are involved.
2.Approximately 70% of patients with complications are older than 50 years of age
3.Prodromal symptoms in the involved dermatome are pruritus, dysesthesia and pain
4.Rarely, nerve pain is not associated with a skin rash
5.The skin rash is composed of grouped vesicles on an erythematous base. The rash begins as red macules and papules that over 7 to 10 days evolve into vesicles, pustules and then scabs. Healing may take more than a month
1.PHN risk increases with age (90 days after the onset of pain); 5% in patients <60, 10% in patients 60 to 69 years of age and 20% in patients older than 80 years of age
2.The pain is neuropathic; it may be intermittent and not correlated with external stimuli
3.Frequently the affected dermatome may have decreased mechanical sensitivity but demonstrates dynamic mechanical allodynia
1.In general, one dorsal root ganglion is most severely involved; adjacent ganglia may show less severe pathology
2.Acutely, the maximally affected ganglion is swollen and congested
3.Microscopically there is lymphocytic and mononuclear cell inflammation
4.Necrosis of the walls of small blood vessels with thrombosis
5.Sensory neurons demonstrate loss of Nissl substance, cytoplasmic eosinophilia and neuronophagia
1.Detection of viral DNA by polymerase chain reaction
2.Herpes zoster lesions contain high concentrations of VZV
1.Primary chest wall tumors are 5% of all thoracic tumors and 0.04% of all primary tumors
2.Approximately 50% are metastatic or direct invasion from adjacent malignancies
1.Intercostal nerve pain as the nerves are infiltrated by tumor
2.Dull boring pain in the area of the primary tumor that evolves into lancinating pain with intercostal nerve involvement
3.Mesothelioma usually invades locally into the chest wall but has been described as causing intercostal neuralgia
1.Metastatic lesions from any cancer but primarily breast, lung, prostate
2.Lymphoma and multiple myeloma
3.Adjacent malignant invasion from:
a.Breast and lung cancer
b.Mesothelioma
c.Mediastinal tumors
1.Medical evaluation to rule out a metastatic lesion
2.Biopsy of the tumor
1.CT and MRI to delineate boundaries of the tumor and detection of its invasion of nerves and vessels
2.18F-FDG accumulation on PET / CT
1.The medial pectoral nerve takes origin from the medial cord of the brachial plexus or as a variant from the anterior division of the inferior trunk
2.It is derived from C8 and T1 roots
3.The nerve lies behind the axillary artery, courses between the axillary artery and vein and anastomoses anterior to the artery from a filament of the lateral pectoral nerve
4.The nerve enters the deep surface of the pectoralis minor muscle to supply the muscle
5.Branches of the nerve terminate in the sternocostal head of the pectoralis major muscle
6.It carries nociceptive and proprioceptive sensory fibers that project to the T1 areas of the anterior chest wall
7.The lateral pectoral nerve takes origin from the lateral cord of the brachial plexus; its roots are C5-C7
8.It courses across the axillary artery and vein, pierces the coracoclavicular fascia and terminates in the deep surface of the pectoralis major muscle
9.It anastomoses with the medial pectoral nerve to form a loop anterior to the proximal part of the axillary artery
10. It splits into 4 to 7 branches that pierce the clavipectoral fascia to innervate the pectoralis major muscle
11. It carries pain fibers to the upper anterior chest wall
1.Breast augmentation surgery is a common procedure with the great majority of implants being placed submuscularly
2.Tissue expansion is a commonly utilized technique for reconstruction of a breast that has undergone surgery for carcinoma
3.Submuscular implant placement causes anterior chest wall pain from stretching of the pectoralis major muscle and resulting muscle spasm
4.Pain may also be perceived in components of the medial and lateral pectoral muscle insertions which include:
a.Insertion of the pectoralis major muscle:
i.Superolaterally into the proximal humerus
ii.Superiorly into the inferior clavicle
iii.Medially into the sternum (extending inferiorly to the seventh rib)
iv.The pectoralis minor muscle inserts superolaterally into the coracoid process of the anterior scapula and inferomedially into the 3-5th ribs
1.The medial and lateral pectoral nerves may be injured with high impact motor vehicle or other forms of blunt trauma (avulsion)
2.They are frequently involved by neuropraxis during the course of submuscular device or tissue expansion reconstructive or breast augmentation surgery
1.EMG
a.To delineate the degree of muscle denervation
1.MRI:
a.To delineate structural lesions in associated traumatic injuries
b.Ultrasound evaluation of the nerves
1.The intercostobrachial nerve is a pure sensory nerve. It arises primarily from the second intercostal nerve and may receive variant contributions from intercostal nerves T1-T4
2.The major anatomical variants of the nerve (100 adult human formalin-fixed cadavers):
a.Type I variant: 45% of patients had a branch from the nerve to the posterior antebrachial cutaneous nerve, a branch to the anterior and lateral areas of the axilla, a branch to the medial aspect of the arm and a branch to the medial antebrachial cutaneous nerve
3.Type II variant: in 25% of patients, the nerve arises from T2 and gives a branch to the brachial plexus
4.Type III variant: in 10% of patients, the lateral cutaneous branches of T2 and T3 fuse as a common trunk and then split after their exit from the intercostal space to form an ICBN
5.Type IV-VII are variants of T2 and T4 recombinations
6.Its extra-thoracic course runs parallel to the axillary vein for approximately 1.5cm in the vertical plane to innervate the axilla, upper medial arm and upper lateral chest wall
7.Most important of its pain radiations when the nerve is stimulated is under the breast to the sternum in the midline
1.The ICBN is most commonly injured during radical mastectomy with axillary lymph node dissection
2.Pain in the sensory distribution of the nerve is described as burning, lancinating or a pressure sensation
3.Complex regional pain syndrome type II has been described primarily affecting the chest wall. It is associated with neurogenic edema, erythema and autonomic dysregulation
1.The nerve is most often damaged during a neuropraxic injury (stretch injury leaving the axon intact); it may be transected as well.
2.The nerve may be damaged from high impact motor vehicle accidents, concomitantly with avulsion of the brachial plexus or severe blunt chest trauma from blast injuries
1.MRI neurography to evaluate the brachial plexus as well as the primary T2 root
2.Ultrasonography to delineate the nerve (ICBN)
1.Post-mastectomy pain syndrome (PMPS) is a chronic pain disorder, most often neuropathic, which occurs following breast surgery
2.Chronic pain occurs after breast procedures that include:
a.Lumpectomy
b.Breast reconstruction
c.Augmentation
d.Reduction
3.Chronic pain persists beyond the normal healing time of 3 months
4.The incidence of the disorder varies from 4-56% described in the past. At present, the incidence of post mastectomy pain is approximately 40%. The risk of PMPs may be increased in younger women. Body mass index does not appear to be a risk factor. Axillary dissection with the removal of 15 nodes is a risk factor
1.The descriptors for pain from the McGill pain questionnaire are stabbing, shooting, aching, gnawing, nagging, tiring and a sensation of tightness
2.The intensity of the pain is variable and most often moderate
3.Sleep is most often unaffected but a subgroup of patients have sleep interruption 2-3 nights / week
4.Pain is exacerbated by straining, lying down, cold weather, mechanical stimuli of the area and getting out of bed. Stretching aggravates the pain
5.Relieving factors in some patients are sitting, while for others it may be recumbency
6.A review of neuropathic pain after breast surgery divided it into four syndromes:
a.Phantom breast pain
b.Intercostobrachial neuralgia
c.Neuroma pain
d.Other nerve pain
1.Primary neuropractic injury or transection of the intercostobrachial nerve
2.Neuromas in the surgical scar
1.MRI neurography to evaluate the ICBN
2.Ultrasonography of ICBN and pectoral nerves
1.Phantom breast syndrome is a disorder in which patients who have had removal of a breast retain the sensation of residual breast tissue. These include non-painful and painful sensations
2.The incidence varies widely and has been reported to affect between 30 to 90% of patients following mastectomy
1.The highest incidence occurs with combined mastectomy and reconstruction
2.Two risk factors for development of phantom breast pain are severe acute postoperative pain and greater postoperative use of analgesics
3.Patients may have pain and discomfort, itching, pins and needles, tingling pressure, burning and throbbing
4.The syndrome may be delayed up to a year after surgery
5.The pain and sensory alterations are localized to the axilla, medial upper arm and anterior chest wall
1.Most often there is neuropractic damage or severance of the branches or complete section of the intercostobrachial nerve
1.Ultrasonography of the intercostobrachial nerve and its branches
1.Terminal branches of thoracic intercostal nerves are entrapped in abdominal muscles that causes severe neuropathic pain
1.The site of abdominal wall tenderness is < 2cm2 that is situated within the lateral boundaries of the rectus abdominis muscle
2.A positive Carnett’s sign in which there is an exacerbation of pain during palpation with contraction of the abdominal musculature. The patient lies flat and flexes the head against resistance
3.Rarely there is hyperalgesia and allodynia to mechanical stimuli of the painful area
1.Entrapment of the anterior cutaneous branches of intercostal nerves from structures of the abdominal wall that include the parietal peritoneum, subcutaneous tissue, aponeurosis and the abdominal muscles
1.Normal laboratory analysis
1.MRI and / or CT to rule out other abdominal pathology
1.The iliohypogastric nerve is mixed and arises from the anterior rami of T12 and L1 nerve roots
2.It courses across the psoas muscle, behind the kidney, crosses the quadratus lumborum muscle to reach the iliac crest. It pierces the internal oblique and transversus abdominis muscles which it innervates
3.Its lateral cutaneous branch innervates the skin over the outer buttock and hip; its anterior cutaneous branch supplies the anterior abdominal wall above the pubis
1.There is little motor deficit
2.Hypoesthesia or mechanical hyperalgesia in the distribution of the anterior or lateral cutaneous branches of the nerve
1.The nerve may be crushed or undergo neuropractic injury from severe pelvic trauma
2.The lateral branch is often injured during iliac crest bone marrow harvesting
3.The nerve is most commonly injured in the lumbar plexus, at the posterior or anterior abdominal wall or distally near the inguinal ring
4.The nerve may be injured during hernia repair
1.Ultrasonography of the nerve
1.The ilioinguinal nerve is mixed and takes origin from the anterior ramus of the first lumbar root. It courses laterally and downwards in parallel with the iliohypogastric nerve to the iliac crest. It supplies the internal oblique and transversus abdominis muscles
2.After innervating these two muscles it enters the inguinal canal, courses to the superficial inguinal ring from which its sensory fibers emerge
3.The sensory innervation is to the medial thigh below the inguinal ligament and the skin of the symphysis pubis and external genitalia
1.Hyper or hypoesthesia of the skin along the inguinal ligament with radiation to the lower abdomen
2.Pain may be localized to the medial groin, the labia majora or the scrotum
3.In approximately 75% of patients there is pain and tenderness with mechanical stimuli applied to the areas where the nerve exits the inguinal canal
4.Symptoms are exacerbated by hip extension
5.Patients may walk with the trunk forward flexed
6.Pain may be elicited by palpation medial to the anterior superior iliac spine
1.Neuropractic or direct injury to the nerve occurs in the lumbar plexus, at the posterior or anterior abdominal wall or within the inguinal canal.
2.The nerve may be injured with herniorrhaphy or appendectomy
3.The nerve is usually entrapped as it passes through the muscles of the abdominal wall medial to the anterior superior iliac spine
4.The nerve may be stretched during pregnancy
5.Trauma to the external oblique muscle and aponeurosis has been described in professional athletes which entraps the nerve in the injured muscle (one form of “sports” hernia)
1.EMG to evaluate denervation in the external oblique muscle
1.Ultrasonography of the nerve
1.The genitofemoral nerve is primarily sensory
2.It arises from the first and second lumbar segments within the psoas muscle. It courses through the psoas muscle and divides near the inguinal ligament into the genital branch and femoral branch (lumboinguinal branch)
3.The external spermatic or genital branch (composed of fibers from L1) enters the deep inguinal ring courses through the inguinal canal and terminates in the cremaster muscle and skin of the scrotum or labia majoris and medial thigh
4.The lumboinguinal or femoral branch arises primarily from L2, courses behind the femoral artery to innervate the skin of the upper thigh and the femoral triangle
1.Pathology of the femoral branch of the nerve causes hypoesthesia over the anterior thigh below the inguinal ligament which distinguishes the nerve from the iliohypogastric or ilioinguinal nerves
2.Groin pain, paresthesias and burning sensation may be perceived from the lower abdomen to the medial thigh
3.There is overlapping sensory innervation with the ilioinguinal and ilio hypogastric nerves
4.Pain can be exacerbated by internal or external rotation of the hip, prolonged walking and mechanical stimuli (if hyperalgesia or allodynia has developed)
5.Loss of the cremasteric reflex
1.The nerve can be injured during inguinal and femoral herniorrhaphy using both open and laparoscopic techniques
2.The nerve may be injured in the lumbar plexus, within the abdomen or in the femoral or inguinal region
1.Nerve conduction velocity
1.Ultrasonography of the nerve
1.Inguinal hernia repair is one of the most common operations worldwide. Chronic postherniorrhaphy inguinal pain is its most feared complication
2.Approximately 800,000 inguinal repairs are performed annually in the USA; possibly the lifetime risk for men is 27% and 3% for women
3.The usual definition of chronic postherniorrhaphy inguinal pain (CPIP) is 3-6 months. The estimate of moderate to severe pain following surgery is 10-12%
4.The possible etiologies of this inguinal pain are:
a.Hernia recurrence
b.Tissue inflammation
c.Meshoma
d.Inguinal nerve injury or entrapment
5.The risk factors are:
a.Female sex
b.Young age
c.High pre and postoperative pain levels
d.CPIP (chronic postsurgical inguinal pain) is independent of technique
e.Preoperative experimental stimuli (response to pain tests) have been shown to predict 4% to 54% of the postoperative pain experience
f.Genetic susceptibility
1.Clinical symptomatology of CPIP has been categorized into:
a.Neuropathic pain
b.Somatic pain
c.Visceral pain
2.Neuropathic pain:
a.Spontaneous pain
b.Hypoesthesia
c.Hyperesthesia and allodynia to mechanical stimuli
d.Burning paresthesia
e.Stabbing, burning, pulling, throbbing, lancinating, sharp and prickling are the most common descriptors
f.The most common sites of pain radiation are the scrotum, labium, and upper thigh
g.Rarely a trigger point can be elicited that produces the pain radiations
h.The pain is exacerbated by walking, twisting or stretching the torso, stooping or sitting, hyperextension of the hip and sexual intercourse
i.A few male patients describe painful ejaculation
j.Relieving factors are recumbency with flexion of the hip and thigh
3.Non-neuropathic pain (inflammatory pain):
a.Dull ache, that is constant and perceived over the entire groin area
b.No trigger points and no pain radiation
c.Descriptors of the pain are: gnawing, tender, pounding or pulling
4.Nociceptive pain:
a.Usually localized to the pubic tubercle
5.Visceral pain:
a.Generally related to sexual dysfunction or ejaculatory pain (usually burning) which is perceived in the region of the superficial ring of the inguinal canal or the testicular or labial region
b.Patients that have had their surgery from an anterior approach may have a tender spermatic cord
c.Abdominal wall laxity from partial denervation of the oblique musculature
1.Entrapment or injury of the iliohypogastric, ilioinguinal, and genital femoral nerves are common causes of CPIP. Operative neurectomy of the three nerves is a common mode of surgical therapy. The entrapment is frequently caused by sutures or fixating devices
2.There is significant anatomical variation of the IHN, IIN and GFN with cross innervation in the retroperitoneum and inguinal canal
3.Meshoma:
a.The mesh is implanted in front of or behind the transversalus fascia; in the latter approach this is done through an open or laparoscopic technique
b.The mesh is implanted without fixation or is fixed by sutures, metallic staples and tacks or various tissue glues
c.Non or insufficient fixation or inadequate dissection for the prosthesis leads to folding and wrinkling of the mesh that continues until the mesh forms a ball, the meshoma
d.Meshomas cause neuropathic pain from nerve entrapment, direct contact with mesh or compression of contiguous tissue which may cause both nociceptive pain or a foreign body feeling
1.Ultrasonography is the best initial modality to detect hernia recurrence or meshoma
2.Cross-sectional computed tomography (CT) and MRI of the abdominal wall are useful to exclude other pathologies and to validate meshoma and recurrent hernia as causative
1.Cholecystitis:
a.Radiation to T6 (tip of the scapula)
2.Cholangitis
3.Pancreatitis:
a.Radiation straight through to the back
4.Hepatitis
5.Budd-Chiari syndrome
6.Subdiaphragmatic abscess
1.Peptic ulcer
2.Gastritis
3.GERD-radiations into the chest and pharynx
4.Pancreatitis
5.Esophagitis-radiation as well into the chest
1.Splenic infarct and rupture:
a.Radiation to the ipsilesional side shoulder
2.Gastritis and gastric ulcer:
a.Diffuse
3.Pancreatitis
4.Subdiaphragmatic abscess
1.Appendicitis
2.Inguinal hernia
3.Nephrolithiasis
4.Inflammatory bowel disease
5.Mesenteric lymphadenitis
6.Typhlitis (recurrent appendiceal infection)
1.Early appendicitis
2.Gastroenteritis
3.Bowel obstruction
1.Diverticulitis
2.Inguinal hernia
3.Nephrolithiasis
4.Irritable bowel syndrome
5.Inflammatory bowel disease
1.The pudendal nerve is a mixed sensory nerve that arises from the lumbosacral plexus. It arises from the ventral rami of S2, S3 and S4 nerve roots.
2.The trunk passes between the coccygeus and pyriformis muscles and exits the pelvis at the lower border of the greater sciatic foramen. At this level it gives off its inferior rectal branch
3.The nerve re-enters the pelvis through the lesser sciatic foramen and traverses distally through the pudendal canal (Alcock’s canal) concomitantly with internal pudendal vessels.
4.Alcock’s canal is located along the lateral wall of the ischiorectal fossa. Its outer covering is the obturator fascia
5.At the level of the perineum, it gives off the perineal nerves and the dorsal nerve of the penis or clitoris.
6.Variants of this classic anatomy are frequent and include:
a.Two pudendal nerve trunks that traverse the sacrotuberous ligament
b.There may be two exits from Alcock’s canal: one for the dorsal branch and one for the perineal branch of the nerve
c.The pudendal nerve may originate from the sciatic nerve. Rarely dorsal rami of the first sacral nerve contribute to the pudendal nerve. Extremely rarely there is a contribution from S5
d.The sensory innervation of the pudendal nerve serves:
i.The penis and clitoris through the dorsal nerve of the penis and dorsal clitoral branches
ii.The posterior scrotal nerves and posterior labial nerves give sensory innervation to the posterior scrotum and the labia respectively
iii.The anal canal
iv.Branches innervate the muscles of the perineum and pelvic floor which include the bulbospongiosus and ischiocavernosus muscles, the levator ani muscle, the iliococcygeus, pubococcygeus, puborectalis, pubovaginalis (females) or the pubourethralis (males), the external anal sphincter and the external urethral sphincter
1.Pain is localized to the vulva, vagina, perineum and rectum in females
2.In males pain is perceived in the glans penis, scrotum (excluding the testicles) perineum and rectum
3.The pain is spontaneous, most often a dull ache or burning, superimposed lancinating pain
4.Mechanical hyperalgesia and allodynia
5.Entrapment of the nerve is characterized by exacerbation of pain with sitting and relief of pain with standing. Pain is usually absent with recumbency or when sitting on a toilet seat
6.Associated signs and symptoms include:
a.Urinary hesitancy and frequency
b.Constipation and painful defection
c.Fecal incontinence
d.Numbness of the penis / scrotum or vulva
e.Altered sensation of ejaculation
f.Impotence in men
1.In entrapment the compression points are:
a.Compression between the sacrotuberous and sacrospinous ligament
b.The falciform process
c.The pudendal canal (Alcock’s canal)
2.Neuropractic injury (the nerves are stretched but the axon is intact). This type of injury occurs with compression of the pelvic floor during childbirth or with chronic straining from severe constipation
3.The nerve may be injured with prolonged cycling (a numb penis or vulva)
4.Removal of pelvic tumors (surgical trauma)
5.Pelvic trauma from high impact injuries
6.Hip surgery
1.Nerve latency testing in muscles supplied by the pudendal nerve
2.Ultrasound cannot identify small areas of scarring in the pelvis along the course of the nerve
3.Magnetic resonance neurography
1.Primary dysmenorrhea is defined as painful menses, primarily cramping, in the lower abdomen often accompanied by hyperhidrosis, headache, nausea, vomiting, diarrhea and tremulousness
2.There is wide variance of prevalence rates with estimates that 2% of adolescent girls have severe pain
1.Cramping pain in the abdomen that occurs just before or during menstruation
2.Some reported prevalence rates are as high as 90%
3.Primary dysmenorrhea usually presents during adolescence or within three years of menarche
4.It is unusual for symptoms to begin prior to six months of menarche
5.Patients have sharp, cramping and intermittent pain that is usually located suprapubically
6.Radiations are to the back of the legs or the lower back
7.Associated symptoms most commonly are nausea, vomiting, fatigue and headache
8.Pain usually starts within hours of the start of menstruation and is most severe with the heaviest flow during the first two days of the cycle
9.The physical examination is normal
10. Symptoms suggestive of a secondary cause of dysmenorrhea:
a.Dysmenorrhea that develops during the first one or two cycles of menarche:
i.Congenital outlet obstruction
b.Dysmenorrhea that develops after 25 years of age
c.Late onset of dysmenorrhea after previous painless menstruation
d.Pelvic anomalies on examination
1.Normal examination with primary dysmenorrhea
2.Causes of secondary dysmenorrhea:
a.Adenomyosis
b.Pelvic inflammatory disease
c.Cervical stenosis and polyps
d.Fibroids (intracavitary or intramural)
e.Endometriosis
f.Inflammation and scarring (surgery with adhesions)
g.Functional ovarian cysts
h.Benign or malignant tumors of the ovary, bowel or bladder
3.Release of prostaglandins may cause abnormal uterine contractions which cause pain
1.Gynecologic ultrasonography
2.Medical evaluation for specific causes of secondary dysmenorrhea
3.Possible laparoscopy
1.Endometriosis is the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. This tissue has the same steroid receptors as the normal endometrium and responds to the normal cyclic hormonal milieu
2.Typically the ectopic implants are located in the pelvis – the ovaries, fallopian tubes, vagina, cervix or the uterosacral ligaments and rectovaginal septum
3.Risk factors include:
a.Family history of endometriosis
b.Early age of menarche
c.Short menstrual cycles (< 27 days)
d.Long duration of menstrual flow (> 7 days)
e.Heavy bleeding during menses
f.Inverse relationship to parity
g.Delayed childbearing
h.Defects in the uterus or fallopian tubes
i.Possible iron deficiency
j.Genetic predisposition
k.CYPIA1 polymorphism has been associated with an increased risk of endometriosis (particularly in Asian women)
l.A patient with a first degree relative with endometriosis has a lifetime risk approximately 10 times that of women without an affected family member
m.If the products of cystic sloughing of endometriotic implants become entrapped by cyst formation, the mass is called an endometrioma. These may occur in any location but are most commonly encountered on one or both ovaries
1.A significant number of patients are asymptomatic (approximately 1/3)
2.Midline implantation may be more painful than lateral disease
3.The location of the pain may be pelvic, lower abdominal or in the back
4.Inguinal pain
5.Patients often present with increasing pelvic pain and/ or secondary dysmenorrhea
6.Painful bowel movements associated with diarrhea in association with menses when endometriosis involves the rectosigmoid colon
7.Flank pain, dysuria or hematuria may occur if the bladder or uterus are affected
8.Depending on the site of implantation cyclic pain with menstruation may involve the bladder, bowel (painful defecation) or bleeding at uncommon sites such as the umbilicus, abdominal wall or perineum
9.The average onset of cyclic or noncyclic pain was 2.9 years after menarche (one large series)
10. Rarely, there can be a cyclically expanding mass in a pelvic surgery scar which is painful
11. Acute exacerbations of pain can occur from rupture of an endometriotic cyst (chemical peritonitis) or implantation in peripheral spinal nerves
12. Deep dyspareunia may occur particularly in the premenstrual phase of the cycle. This pain may be due to scarring of the uterosacral ligaments, nodularity of the rectovaginal septum, cul-de-sac obliteration
13. The most common physical finding is nonspecific pelvic tenderness
14. Pelvic examination may reveal tender nodular masses along thickened uterosacral ligaments, the posterior uterus or the posterior cul-de-sac
15. Pain may be exacerbated by exercise, micturition and defecation
1.Ectopic endometrial tissue is most commonly encountered in the dependent areas of the pelvis which include the anterior and posterior cul-de-sac, the uterosacral ligaments, fallopian tubes and ovaries
2.The sloughed endometrial tissue and release of cytokines and prostaglandins induce an inflammatory response characterized by neovascularization and fibrosis
3.There is evidence of altered T and B cell function, complement deposition and increased IL-6 production
4.In endometriosis, there may be an aberrantly expressed factor SF-1 that induces the expression of aromatase. Aromatase converts C19 steroids to estrogen. Estrogen increases the synthesis of prostaglandin E2 that stimulates the uterus and induces aromatase.
5.Recent studies have demonstrated increased expression of neurotrophic factors and nerve fibers in endometriotic lesions, eutopic endometrium and the peritoneum which may be related to endometriosis pain
1.Pelvic ultrasonography, CT and MRI are only useful in advanced disease
2.Laparoscopy to directly visualize endometrial implants
1.Vulvodynia is a chronic pain condition that affects the vulvar area. The condition must last for at least 3 months to meet diagnostic criteria
2.It has been estimated to affect as many as 16% of women
1.Pain is the most disabling symptom
2.There is burning, stinging or lancinating pain that can be continuous or occurs only with mechanical stimuli
3.Symptoms may be localized or affect the entire vulvar area
4.It can occur during or after sexual activity or when prolonged pressure is applied to the area from activities of daily living
5.Vulvar vestibulitis syndrome (VVS) is pain localized to the vestibular area
6.It is the most common subtype of vulvodynia and has been estimated to affect 10 to 15% of premenstrual women that present to gynecologists
7.The pain is usually described as neuropathic in quality
1.The cause of vulvodynia is incompletely understood. At present, it appears to be heterogeneous.
2.Proposed mechanisms include:
a.Infections that include yeast, bacterial vaginosis, HPV, HSV
b.Genetic predisposition to inflammation
c.An autoimmune disorder
d.Injury
e.Possible use of hormonal contraceptives that contain low-dose estrogen prior to age 16
f.Pelvic floor dysfunction
g.Recent experimental evidence has demonstrated:
i.Site-specific inflammatory responses
ii.Fibroblasts isolated from the vestibule in patients are sensitive to proinflammatory stimuli and release inflammatory mediators that include IL-6 and PGE2.
1.Wet mount of vaginal secretions, vaginal pH, fungal culture and Gram stain
1.Candidiasis, herpes and HPV
2.Lichen planus
3.Paget’s disease and vulvar carcinoma
4.Neuralgia secondary to herpes virus
1.Dyspareunia is painful sexual intercourse that is multifactorial and is due to medical or psychological causes
2.It has recently been proposed that the diagnosis of vaginismus and dyspareunia be combined into the diagnostic entity of genito-pelvic-pain / penetration disorder with the following criteria:
a.Percentage success of vaginal penetration
b.Pain with vaginal penetration
c.Fear of vaginal penetration or of genito-pelvic pain during vaginal penetration
d.Pelvic floor muscle dysfunction
e.Medical co-morbidity
1.Pain on attempted intercourse is described as superficial when perceived at the entrance to the vagina or surface of the genitalia and deep when initiated from the vault of the vagina
2.A proportion of women experience pain in more than one area
3.A subset of patients have had pain with intercourse from their first experiences while others develop it after an injury, infection or cyclically with menstruation
4.Pain is increased when the vagina in dry or undilated
5.Fear of pain exacerbates the discomfort
6.External genitalia may demonstrate lesions, thin skin, ulceration or discharge from vulvovaginal infections
7.Internal pelvic exam may demonstrate cervical lesions and anatomical variations of the uterus
1.Conditions that affect the surface of the vulva include:
a.Lichen sclerosus et atrophicus
b.Xerosis (particularly after menopause)
c.Sjogren’s syndrome (dryness)
2.Infections that primarily affect the labia, vagina or lower urinary tract and include:
a.Yeast infections
b.Chlamydia
c.Trichomoniasis
d.Urinary tract infection
e.Herpes
3.The above conditions cause surface genitalia primarily neuropathic pain often with mechanical hyperalgesia and less frequently allodynia
4.Infection of the cervix or fallopian tubes from pelvic inflammatory disease (PID) cause deeper pain
5.Pain from tissue injury occurs after surgery, childbirth or pelvic trauma
6.Associated anatomic variants that may be a component of pain include:
a.Hymenal remnants
b.Vaginal septa
c.Thickened undilatable hymen
d.Hypoplasia of the introitus, retroverted uterus or prolapse
7.Hormonal effects:
a.Endometriosis and adenomyosis
b.Estrogen deficiency that is associated with lubrication inadequacy
8.Deep vaginal pain can be caused by ovarian cysts, tumors and uterine fibroids
9.Interstitial cystitis:
a.May cause pain during or after sex in women
b.In men with interstitial cystitis pain occurs with ejaculation and radiates to the tip of the penis
c.In females with interstitial cystitis pain is usually felt the following day and is thought to occur from spasm of the pelvic floor musculature
1.Medical evaluation to rule out infection, hormonal deficiency and autoimmune causes
1.MRI
a.To delineate anatomical variants and pathologies such as ovarian tumor or endometriosis
1.Superficial dyspareunia:
a.Infection
b.Inflammation
c.Anatomic variants
d.Tissue damage
e.Psychosocial factors
f.Pelvic floor muscle dysfunction
2.Deep dyspareunia:
a.Endometriosis
b.Ovarian cysts
c.Pelvic inflammatory disease
d.Psychosocial factors
1.Prostodynia or chronic pelvic pain syndrome is utilized for unexplained chronic pelvic pain in men
2.The National Institutes of Health designation of categories of prostatitis is:
a.Type I - Acute bacterial prostatitis
b.Type II - Chronic bacterial prostatitis
c.Type III - Chronic abacterial prostatitis
i.IIIa – inflammatory
ii.IIIb – noninflammatory
d.Type IV - Asymptomatic inflammatory prostatitis
3.The majority of chronic prostatitis patients are type III (approximately 90-95%), without infection but with chronic pelvic pain. The chronic pelvic pain symptoms last for at least three to six months without a cause related to urinary tract infection or malignancy.
4.Worldwide it is estimated that 2 to 14% of men have CP / CPPS
1.The usual patient is a young to middle-aged man
2.The pain is localized:
a.Between the rectum and testicles
b.In the testicles
c.In the tip of the penis
d.Below the waist
3.The pain is usually moderate but can be severe and is usually a dull ache
4.The sensation of not emptying the bladder completely
5.Irritative and obstructive bladder symptomatology
6.Erectile dysfunction; pain with sitting
7.Anal sphincter tone may be increased
8.The prostate may have moderate to severe mechanical hyperalgesia
9.The gland may be slightly congested
1.In the past infection, immunologic dysfunction and psychosocial issues have been proffered as causative
2.Organic and morphological pathology does not explain the chronic pelvic pain
3.Present theories for cause include:
a.Stress-driven hypothalamic-pituitary-adrenal axis dysfunction
b.Neurogenic inflammation
c.Myofascial pain syndrome
1.There are no definitive diagnostic tests for CP / CPPS
2.Categorization as IIIa (inflammatory) or non-inflammatory IIIb is based on levels of leukocytes in expressed prostatic secretions
3.TGFΒ 1 and IFN-γ have been shown to be increased in some patients with IIIa and IIIb disease
4.There is some evidence that nerve growth factor could be a biomarker of the disorder
5.Semen and prostatic fluid evaluation have shown elevated cytokines, myeloperoxidase and chemokines
6.Flexible cystoscopy (rule out bladder conditions)
7.Urodynamic tests to rule out bladder neck hypertrophy and urethral stricture
1.The de facto definition of the disease has been the modified National Institute of Diabetes and Digestive and Kidney Diseases NIDDK criteria which has been used and include:
a.2 inclusion criteria and 1 exclusion criterion
b.At least 1 subjective symptom and 1 cystoscopic finding
2.Subjective symptoms:
a.Pain associated with the bladder
b.Urinary urgency
3.Cystoscopic criteria include:
a.Glomerulations in at least 3 quadrants of the bladder and at least 10 glomerulations per quadrant (a glomerulation is a petechial hemorrhage of the bladder wall)
b.Classic Hunner ulcer:
i.Distinctive areas of inflammation on the bladder wall
ii.Glomerulations cannot be along the path of the cystoscope
4.Exclusion criteria for interstitial cystitis:
a.Cystometric bladder capacity > than 350 ml
b.Absence of an urge to void when the bladder has been filled with 100ml of liquid
c.Phasic involuntary bladder contractions at a fill rate of 30-100ml
i.Detrussor instability occurs in 14% of patients with IC
d.Symptom duration of less than 9 months
e.Nocturia
f.Symptoms are relieved by antimicrobials, antiseptics, anticholinergics or antispasmodics
g.Micturition frequency of less than 8 times daily
1.Day and night time frequency
2.Pelvic pain or pressure
3.Suprapubic pain related to bladder filling
1.Findings in cystoscopy under anesthesia:
a.Inflammatory infiltrate
b.Granulation tissue
c.Detrusor mastocytosis
d.Intrafascicular fibrosis
e.Hunner’s ulcer (patches of reddened mucosa with small vessels radiating from a central pale scar)
f.Nonulcer IC:
i.Multiple strawberry-like petechial hemorrhages (“glomerulations”)
1.Inflammatory mediators as urinary markers of IC / BPS syndrome (bladder pain syndrome) include:
a.Mast cells, histamine and methylhistamine
b.NGF
c.IL-6, CRP, CXCL10 (chemokine), CXCR3, TNIFSF14
2.Elevated proliferative factors have been demonstrated and include:
a.PD-ECGF, UEGF, NGF, EGF and HB-EGF
b.Antiproliferative factor (APF):
i.Possibly the most promising biomarker
ii.It is a sialogy copeptide and inhibits endothelial proliferation
iii.Moderates the cell cycle by G2 blockage
iv.Has been detected in the urine of 95% of IC patients
3.Cystoscopy
Scrotal pain is a common condition in urologic practice. It can present acutely or more commonly in chronic form. The more common urological problems are testicular torsion, epididymitis, postvasectomy pain, varicocele, and chronic orchalgia. Nonurological causes of scrotal pain are peritonitis, incarcerated hernia, ruptured abdominal aortic aneurysm, and referred scrotal pain.
The sensory innervation of the upper ureter and testes traverse spinal cord levels T11 and T12. Upper ureteral distension (stone or malignancy) refers pain to the testis (somatic-visceral convergence at these dorsal root ganglia). Lower ureteral distension causes ipsilateral scrotal pain. Less frequent causes of scrotal pain are Henoch-Schonlein purpura, testicular tumors and referred pain from disc or other vertebral pathologies (T10-L1 segments). Extremely rarely, it may be caused by a partial complex seizure that involves the cortical genital area. Testicular tumors primarily present as a painless scrotal mass. A rapidly growing tumor may have internal bleeding or infarction that presents as scrotal pain.
1.Testicular torsion is a medical emergency. The incidence is 1 in 4000 males < than 25 years of age
1.The classic presentation is the acute onset of intense unilateral scrotal pain often associated with nausea and vomiting
2.Patients may have a history of prior scrotal pain that resolved spontaneously (ischemic episodes)
3.“High riding” testicle due to shortening of the cord; the testicle may be transverse in the scrotum
4.Loss of the cremasteric reflex is common in pediatric patients
5.Testicular torsion usually occurs around puberty while epididymitis affects sexually active men after the age of 20
6.Patients with torsion of a testicular appendage such as an appendix testis or appendix epididymis have:
a.Rare systemic complaints
b.Gradual onset, less intense, unilateral scrotal pain that is localized to the superior pole of the testis
c.The scrotal skin may reveal the “blue dot” sign from the nonviable appendage
1.Testicular torsion may be intravaginal or extravaginal that typically occurs in neonates and in adolescents prior to complete testicular descent and scrotal wall fusion
a.Intravaginal torsion:
i.The testicle can rotate within the tunica vaginalis due to the congenital bell clapper anomaly. This anomaly is due to failure of a posterior anchor for the gubernaculum (the scrotal ligament, which secures the testis to the most inferior portion of the scrotum), epididymis and testis; this allows the testis to rotate within the tunica vaginalis
b.Extravaginal torsion:
i.The testis rotates within the scrotum due to inadequate fusion of the testicle to the scrotal wall
ii.The torsion is caused by rotation of the spermatic cord and causes ischemia
iii.Torsion of testicular appendages:
1.Occurs in 7-13 year-old children
2.Similar clinical presentation to testicular torsion
3.Accounts for 24-46% of acute scrotal presentations
1.Urinalysis:
a.Hematuria or leukocytosis is more typical of epididymo-orchitis rather than torsion
b.Doppler ultrasonography
i.Assess testicular blood flow
1.Epididymitis may cause acute scrotal pain that must be differentiated from testicular torsion
2.A painful parenchymal inflammatory process that causes epididymal swelling
1.Primarily encountered in men between 18-50 years of age; in pediatric patients, the peak incidence is during puberty
2.Infantile epididymitis is associated with other urogenital anomalies
3.Epididymitis presents with gradually increasing dull unilateral scrotal pain
4.Vasa involvement may be associated with exquisite pain that localizes to the entire hemiscrotum and the spermatic cord
5.The epididymis is swollen and tender; the cremasteric reflex is intact
6.There has often been a recent GU procedure or sexual activity
1.If the swelling affects the testicles the disorder is defined as epididymo-orchitis
2.The most common organisms are dependent on age and sexual activity
3.The pathophysiology of the disorder is the spread of microorganisms from the urethra, prostate or seminal vesicles or rarely hematogenous spread (tbc) that causes a painful inflammatory process in the epididymis
4.Sexually active men <35 years of age are usually infected with Chlamydia Trachomatis and Neisseria gonorrhoeae
5.Older patients, those that have undergone recent genitourinary surgery or those with anatomical anomalies are usually infected with gram negative enterococci
1.Urinalysis, urine cultures and urethral cultures to identify causative organisms
2.Color Doppler ultrasound or nuclear scintigraphy to assess scrotal blood flow (increased blood flow due to inflammation)
1.Chronic scrotal pain affects up to 15% of patients after vasectomy
1.Patients have scrotal pain and discomfort
2.Pain may be exacerbated or initiated during intercourse, pain with ejaculation and epididymal pain
3.Physical examination reveals:
a.Tender epididymides
b.Swollen epididymides
c.Tender vasectomy site
d.Palpable nodule
1.The pathophysiology is not known but putative mechanisms include:
a.Tender sperm granuloma
b.Nerve entrapment
c.Nerve proliferation at the operative vasectomy site
d.Perineural fibrosis
e.Mechanical duct obstruction with epididymal congestion
2.Histological evaluation:
a.Epididymal engorgement
b.Complex cystic disease
c.Chronic epididymides
1.Ultrasonography with Doppler may demonstrate:
a.Epididymal thickening
b.Epididymal tubular ectasia
c.Blood flow
1.Definition:
a.A varicocele is an abnormal dilation of the spermatic veins due to an anatomical anomaly
b.The incidence is 10-20% in the general male population and 2 to 15% in adolescents
c.Varicoceles are associated with male infertility possibly due to increased temperature, stasis induced hypoxia and reflux of renal and adrenal metabolites
1.The pain associated with a varicocele is dull and aching in quality and less frequently throbbing
2.The pain is localized to the scrotum. There are no lancinating or referred components
3.The pain is exacerbated by long episodes of standing (causes increased hydrostatic pressure in the valveless veins of the pampiniform plexus)
4.Physical examination of the scrotum reveals a “bag of worms” on palpation
5.Classification of varicoceles:
a.Grade 0: No palpable varicocele
b.Grade 1: Palpable during a Valsalva maneuver
c.Grade 2: Visible in the standing position during a Valsalva maneuver
d.Grade 3: Visible in the standing position through scrotal skin without a Valsalva maneuver
1.The putative mechanism is thought to be absent or malfunction of vein valves that allow retrograde flow into the pampiniform plexus. The plexus is located in the spermatic cord and scrotum that is derived from the internal spermatic and cremasteric veins. There may be lack of valves proximal to the renal veins and absent or incomplete valves along the internal spermatic vein. Varicoceles may be more frequent on the left side as the left gonadal vein is longer than the right (resulting in greater hydrostatic pressure) and it inserts into the left renal vein
1.Evidence of venous dilation and reflux during a Valsalva maneuver by color Doppler
2.Vein diameter of 2.45mm at rest and 2.95mm during Valsalva maneuver can be demonstrated in grade 1-3 varicoceles.
1.It is defined as intermittent or constant testicular pain of at least 3 months duration that interferes with daily activities
2.50% of patients present with an idiopathic etiology
3.In the USA it may affect up to 100,000 men /year
1.Moderate to severe dull aching pain in the testicle
2.In patients with a neuropathic etiology there may be mechanical hyperalgesia
1.The causal spectrum of chronic orchialgia is wide and includes:
a.Vasectomy
b.Inguinal hernia surgery
c.Recurrent epididymitis
d.Varicocele and hydrocele
e.Prior scrotal or abdominal surgery
f.Trauma
g.Idiopathic
2.Less frequent pathologies are:
a.Diabetic neuropathy
b.Retroperitoneal tumor
c.Abdominal aortic aneurysm
d.Polyarteritis nodosa
3.The ilioinguinal, genital branch of the genitofemoral or pudendal nerves are the most commonly affected nerves. They have been hypothesized to have undergone maladaptive neuroplasticity to produce neuropathic pain
4.Contralateral pain phenomena can occur due to decussation of the nerves in the pelvic plexus
5.An anatomical study has demonstrated a high density of nerve fibers undergoing Wallerian degeneration (that induced an immune response from neutrophils, macrophages and cytokines) in the spermatic cord:
a.Cremasteric muscle fibers
b.Perivasal tissues and vasal sheath
c.Posterior peri-arterial lipomatous tissue
1.Medical evaluation to rule out diabetes mellitus, periarteritis, inguinal hernia and possible referred pain
1.Abdominal MRI to delineate possible sources of referred pain (ureteral stones, hernia, disc)
2.Scrotal Doppler
1.The pelvic floor or pelvic diaphragm is composed of the muscle fibers of the levator ani and the coccygeus muscle and associated connective tissue
2.The levator ani are horizontal in the floor of the pelvis; and are divided into three divisions:
a.The pubococcygeus is the major portion of the levator and courses from the body of the pubis to the coccyx. There is some insertion into the prostate, urethra and vagina
b.The two sides of the puborectalis muscles merge behind the anorectal junction to form a muscular sling. It has been proposed that these muscles are part of the sphincter ani externus
c.The iliococcygeus muscle is the most posterior portion of the levator ani and may be poorly developed
3.The pelvic cavity is delineated by:
a.The pelvic floor is the inferior boundary
b.The pelvic brim is the superior border
c.The perineum’s superior border is the pelvic floor
d.Posteriorly the pelvic floor extends into the anal triangle
e.The hiatuses of the pelvic floor are:
i.The urogenital hiatus is anterior through which the urethra and vagina pass
ii.The rectal hiatus is posterior through which the anal canal traverses
f.The pelvic floor is essential in the support of pelvic viscera and continence as it is a component of the urinary and anal sphincters. During childbirth, it is important in resisting descent of the presenting part which rotates the fetus forward and enables it to pass the pelvic girdle
g.Pelvic floor dysfunction is extremely common and has been estimated to affect 50% of women at some time during their lifetime.
1.Patients complain of pelvic pain, heaviness and aching
2.Pain may be exacerbated by exertion, defecation, sitting and coitus
3.Postcoital pain may be long-lasting and persist for hours to days
4.Pain may radiate to the hip or lower back
5.Physical examination (intravaginal) may demonstrate banding, spasm or tenderness
6.Spasm of a portion of the levator ani is a palpable band
7.In healthy control patients, palpation of the levator ani and piriformis muscle is perceived as pressure. In patients with pelvic floor myalgia this maneuver causes hyperalgesia
8.Examination often reveals asymmetry between the right and left pelvic diaphragm. Spasm and contracture is ipsilateral to the patient’s pain
9.In men with chronic prostatitis / chronic pelvic pain syndrome, myofascial trigger points in pelvic musculature have been identified
1.The major mechanisms of pelvic floor dysfunction are widening of the pelvic floor hiatus and descent of the pelvic floor below the pubococcygeal line
2.Co-morbidities include obesity, menopause, pregnancy and difficult childbirth
3.Myofascial pain / pelvic floor hypertonia often co-exist with other illnesses thought to have a component of central sensitization and include:
a.Endometriosis
b.Painful bladder syndrome / interstitial cystitis
c.Vulvodynia
d.Irritable bowel syndrome
e.Primary dysmenorrhea
4.The levator muscles and their nerve supply can be damaged in pregnancy and childbirth. They may also be damaged during hysterectomy
5.The perineal approach for pelvic surgery, between the anus and coccyx may damage the pelvic floor
6.Rarer causes of damage to the perineum and pelvic floor have been described with water-skiing, bicycle racing and equestrian sports
7.Damage to the pelvic floor that is severe causes urinary incontinence and pelvic organ prolapse in which the vagina, bladder, rectum or uterus protrude into or outside of the vagina
1.Grading of pelvic floor dysfunction by MRI:
a.The pubococcygeal line connects the inferior margin of the pubic symphysis at the midline with the junction of the first and second coccygeal elements on a sagittal image
b.The second landmark is the puborectalis muscle sling
c.A perpendicular line between the pubococcygeal line and muscle sling is a measurement of pelvic floor descent
d.A descent greater than 2cm is mild and 6cm is severe
e.A line from the pubic symphysis to the puborectalis muscle sling is a measurement of the pelvic floor hiatus. Greater than 6cm is mild and 10cm is severe. The degree of organ prolapse is measured relative to the hiatus. Any organ prolapse relative to the hiatus is abnormal and greater than 4cm is severe
1.Chronic pelvic pain lasts for at least 6 months and is of sufficient intensity to disrupt activities of daily living and requires medical or surgical treatment
2.Chronic cyclic pelvic pain (CCPP) is considered to be a subset of chronic pelvic pain that most often occurs with the menstrual cycle. Cyclic chronic pelvic pain also occurs with disorders that have a cyclic pattern that are not related to menstruation or hormonal fluctuations and include:
a.Coital pain
b.Pelvic floor myalgia
c.Provoked vestibulodynia
d.Pudendal neuralgia
e.Ovulation that cause mittelschmerz pain
3.Interstitial cystitis and irritable bowel syndrome occur without a specific pattern but can be exacerbated by menstruation
1.The quality of the pain in the pelvis is usually a dull ache. There may be intermittent lancinating pains: cramping, pressure or heaviness deep in the pelvis are also descriptors
2.Pain may be exacerbated during intercourse, defecation, or micturition. It may be increased by sitting
3.Less frequently pain may be exacerbated by standing or relieved with recumbency
1.Endometriosis
2.Endosalpingiosis
3.Pelvic adhesions
4.Ovarian remnant syndrome
5.Interstitial cystitis
6.Adenomyosis
7.Uterine leiomysis
8.Endometriosis affects approximately 50% of women with CPP:
a.This diagnosis requires visual confirmation of the lesion during laparoscopy and histologic evidence of endometrial glands and stroma
9.Interstitial cystitis is often associated with CPP whose pathology is thought to be bladder epithelial dysfunction, mast cell activation, and peripheral sensitization of bladder nociceptive afferents. There may be increased permeability of the bladder epithelium that can be demonstrated by the Potassium Sensitivity Test. A large proportion of patients with IC may have concomitant endometriosis
10. After adjusting for age and education, women in all subgroups of chronic pelvic pain were found to have lower pain thresholds (increased pressure pain) than healthy controls. This supports the concept that central pain amplification may be a component of CPP
1.Urinalysis and urine cytology
2.Urine and genital cultures
3.Mycoplasma and urealyticum (genital mycoplasma organism) cultures of the vaginal fornix
4.Bladder potassium sensitivity test
5.Laparoscopy
6.Cystoscopy (if IC symptoms are present)
7.MRI of the pelvis to delineate any structural lesions
1.The vast majority of ovarian cysts are benign and asymptomatic. They are detected incidentally by ultrasonography or on routine pelvic examination
1.Pain or discomfort in the lower abdomen or pelvis:
a.Severe pain occurs with torsion or rupture that is characterized by:
i.Sudden onset
ii.Unilateral pelvic pain
iii.Lancinating sharp quality
iv.Associated peritoneal signs and abdominal distension
2.Moderate to large cysts:
a.Dyspareunia particularly with deep penetration
b.Increased urge to defecate (pressure on the bowel or rectum)
c.Frequent micturition (bladder pressure)
d.Abnormalities of the menstrual cycle:
i.Irregularity
ii.Abnormal vaginal bleeding
iii.Prolongation of the intermenstrual interval followed by menorrhagia
e.Abdominal fullness and bloating
f.Indigestion, symptoms of esophageal reflux and early satiety
g.Endometriomas:
i.Associated with endometriosis
ii.Heavy menstrual bleeding
iii.Dyspareunia
h.Polycystic ovarian syndrome:
i.Hirsutism
ii.Infertility
iii.Oligomenorrhea
iv.Obesity
v.Acne
i.Dull bilateral pelvic pain:
i.Theca-lutein cysts
j.Hyperpyrexia – due to ovarian torsion
k.Adnexal or cervical motion tenderness
l.Malignant disease:
i.Cachexia
ii.Weight loss
iii.Lymphadenopathy in the neck
iv.Shortness of breath
v.Pleural effusion
m.Symptoms of early ovarian cancer may include:
i.Unexplained pelvic or abdominal pain
ii.Unexplained bloating
iii.Early satiety
1.Features of an ovarian mass that suggest malignancy are:
a.Large mass with irregularity
b.Complexity and projections
c.Projections and septations
d.Bilaterality
2.Benign cysts:
a.The most common is a functional cyst that forms during ovulation:
i.Either the egg is not released or the follicle in which the egg forms does not dissolve after the egg is released
b.Polycystic ovaries:
i.The follicles fail to open and cysts form
c.Endometriosis:
i.Endometrial tissue attaches to the ovary
d.Cystadenoma:
i.Form on the surface of the ovary and are often fluid-filled
e.Dermoid cysts:
i.Contain skin, hair and rarely teeth
f.Malignant tumors of the ovary:
i.Ovarian carcinomas:
1.Serous
2.Clear cell
3.Mucinous
4.Endometriotic
ii.Germ cell tumors
iii.Stromal tumors
1.Complete blood count
2.Urinalysis
3.Urinary pregnancy test
4.Rh status
5.Cancer antigen 125 (CA125), HE4 markers (upregulated gene in epithelial ovarian carcinoma) may be more sensitive than 125CA
6.ROMA (Risk of Ovarian Malignancy Algorithm):
a.Utilizes the combination of human epididymis protein 4 (HE4) and CA125 values to predict the risk of epithelial ovarian cancer in post-menopausal women but not in pre-menopausal women
7.Matrix metalloproteinase III (MM3) is good to differentiate benign ovarian cysts from ovarian cancer in post-menopausal women
1.Transvaginal ultrasonography is the first imaging choice
2.CT / MRI of the pelvis and abdomen if the mass is larger than 6cm or if there are extraadnexal symptoms or signs
1.An ectopic pregnancy is the implantation of a fertilized egg outside of the uterine cavity
2.The most common locations are:
a.The fallopian tubes (98%)
b.Cervix, ovary, cornual region of the uterus and abdominal cavity
c.In tubal pregnancies the most common sites of implantation are:
i.Ampulla (80%)
ii.Isthmus (12%)
iii.Cornua (2%)
iv.Interstitia (2-3%)
v.Fimbrial (5%)
3.Ectopic pregnancy is estimated to occur in 1 of 40 pregnancies or 25 patients / 1000 pregnancies in the USA
1.The classic clinical triad is abdominal or pelvic pain, amenorrhea, and vaginal bleeding.
a.Approximately 50% of patients present with the entire triad.
2.40 to 50% of patients have vaginal bleeding
3.50% have a palpable adnexal mass
4.75% have abdominal tenderness
5.Patients may present with symptoms of early pregnancy that include:
a.Nausea
b.Breast fullness
c.Fatigue
d.Low abdominal pain
e.Shoulder pain
f.Severe cramping
g.Dyspareunia
6.Unruptured patients:
a.Peritoneal signs
b.Cervical motion tenderness
c.Unilateral or bilateral abdominal or pelvic tenderness worse on the affected side
d.Painful fetal movement (in advanced pregnancy)
e.Dizziness and weakness
f.Fever
g.Flu-like symptoms
h.Vomiting
i.Syncope
j.Cardiac arrest
7.Ruptured ectopic pregnancy
a.A surgical emergency:
i.Hypovolemic shock with orthostatic hypotension and tachycardia
ii.Abdominal rigidity, guarding and severe tenderness
iii.Uterine or cervical motion tenderness
iv.May be difficult to delineate an abdominal mass
1.Uterine contents in the vagina from shedding of the endometrial lining
1.The Β-HCG levels doubles every 48-72 hours in a normal pregnancy until it reaches 10,000-20,000mIU/ml. Mean serum Β-HCG levels are lower with ectopic pregnancy
2.The discriminatory zone of Β-HCG:
a.Defined as the level of Β-HCG that should be attained when an imaging scan demonstrates a gestational sac within the uterus:
i.1500-1800mIU/ml with transvaginal ultrasonography; up to 2300 mIU/ml with multiple gestates
ii.6000-6500mIU/ml with abdominal ultrasonography
3.Ultrasonography
4.Laparoscopy:
a.Most often used for patients in pain or for those that are hemodynamically unstable
1.Fibroids are benign smooth muscle tumors of the uterus
2.Genetic influence in the pathogenesis of fibroids is demonstrated by:
a.The daughter of a mother with fibroids has a three times higher incidence of fibroids than the average woman
3.Familial leiomyomata (Reed’s syndrome):
a.Caused by a mutation located on the long arm of chromosome 1q42.3-43 in the gene FH that encodes fumarate hydratase which is transmitted in an autosomal dominant manner: also associated with renal cell cancer
4.One form of uterine leiomyoma (UL) is due to fusion between an isoform of the recombinational repair gene RAD51B and the high mobility group protein gene HMG1C that maps to chromosome 12q14.3
5.Uterine leiomyomas are associated with other fusion partners of the HMG1C gene that include:
a.ALDH2
b.COX6C
c.HEI10
6.Gene wide association studies have recently revealed loci in chromosome 10q24.33, 22q13.1 and 11p15.5 that are associated with uterine fibroids
7.Locations include:
a.Intramural
b.Subserosal
c.Submucosal
d.Cervical
e.Rarely in the round ligament or uterosacral ligament
8.Most fibroids start in the wall of the uterus and may grow outwardly or toward the uterine cavity
9.Extrauterine fibroids of uterine origin occur rarely:
a.Fibroids that metastasize:
i.Invade the vasculature
ii.Intravenous leiomyomata grow in veins with uterine fibroids
iii.Benign metastasizing fibroids have been demonstrated in the lungs and lymph nodes
iv.Disseminated intraperitoneal leiomyomatosis:
1.The source is uterine fibroids
2.The leiomyomata grow diffusely on the peritoneal and omental surfaces
1.Small fibroids are often asymptomatic; symptoms depend on the location and size of the leiomyoma
2.Abnormal uterine bleeding
3.Heavy or painful menstrual periods
4.Abdominal discomfort and bloating
5.Painful defecation
6.Frequency of micturition and rarely urinary retention
7.Dyspareunia and pelvic pain
8.Miscarriage, bleeding, premature labor
9.Infrequent cause of infertility (location is primarily submucosal)
1.Leiomyomas demonstrate karyotypical chromosomal defects in approximately 40 to 50% of patients.
2.Mutations of the MED12 protein are commonly characterized
3.Genetic predisposition, prenatal hormone exposure and hormone growth factors and xenoestrogens are postulated as factors in their growth
4.Significant risk factors are:
a.African ethnicity
b.Obesity
c.Polycystic ovary syndrome
d.Diabetes mellitus
e.Hypertension
f.Never having given birth
5.Estrogen and progesterone have a mitogenic effect on leiomyomata as well as interacting with growth factors, cytokines and apoptotic factors and hormones
6.It has been hypothesized that estrogen induces leiomyoma growth by up-regulating IGF1, EGFR, TGF-beta 1, TGF-beta 3 and PDGF
7.Estrogen may sustain survival or aberrant leiomyoma by down-regulating:
a.P53
b.Increasing expression of the anti-apoptotic factor PCP4,
c.Blocking PPAR-gamma signaling
8.Progesterone influences leiomyoma growth by upregulating EGF, TGE-beta 1 and TGF-beta 3:
a.Influences survival by up-regulating Bcl-2 expression and down-regulating TNF-alpha
9.Secondary changes that may develop within fibroids are:
a.Hemorrhage
b.Necrosis and cystic changes
c.Calcify after menopause
1.Gynecologic ultrasonography is the standard imaging techniques and demonstrates:
a.Leiomyomas as focal masses with a heterogeneous texture
b.Shadowing of the ultrasound beam
c.Location and dimensions of the mass can be determined
2.Other imaging techniques that may be used to evaluate the uterine cavity are:
a.MRI
b.Hysterosalpingography
c.Sonohysterography
3.Imaging modalities cannot discriminate between benign uterine leiomyoma and malignant leiomyosarcoma. Distinguishing characteristics are:
a.Fast or unexpected growth, as the usual pattern of growth is slow and associated with extracellular matrix
b.Enlargement of a lesion after menopause
c.Local invasion
1.Surgically induced neuropathic pain is estimated to occur in 10 to 50% of patients that have undergone common surgical procedures
2.SNPP occurs in:
a.60% of patients after limb amputation
b.20 to 40% of patients after mastectomy
c.20 to 40% after thoracotomy
d.20% following hernia repair
1.Some patients develop SNPP almost immediately after their procedure while it develops in others weeks or months following injury
2.Spontaneous pain that is burning or aching in quality
3.The pain may be lancinating on a background of burning or a dull aching sensation
4.There may be hypoesthesia in an area of nerve injury or mechanical and thermal hyperalgesia
5.Complex regional pain syndromes type I and II have been described from almost all surgical procedures and demonstrate:
a.Severe spontaneous pain that spreads out of a dermatomal and nerve distribution. A mirror distribution of pain is common and in some patients, the pain becomes generalized. Dynamic and static mechanoallodynia and hyperalgesia are prominent as are thermal hyperalgesia particularly to cold.
b.Autonomic dysregulation is prominent with earlier stages most often producing a warm extremity that evolves over time to a cold discolored extremity with livedo reticularis and cyanosis:
i.Neurogenic edema is present in the great majority of patients
c.A motor syndrome is seen in which patients have difficulty initiating movement, are weak and may develop tremor, atrophy and dystonia
d.Dystrophic changes evolve in hair, muscle, subcutaneous tissue and bone
1.During surgical procedures nerves may be completely transected or undergo neuropractic injury in which the axon may be injured but remains intact
2.The nerve injury causes peripheral sensitization in which the threshold to discharge nociceptive afferents is lowered and central sensitization is produced. In this state, there are major changes in the pain matrix (those areas of the CNS that process pain) which lead to:
a.Enlargement of nociceptive pain projecting neuron receptive fields
b.Loss of inhibition at all levels of the pain matrix
c.Spontaneous and evoked pain
d.Emotional and motivational changes
1.Imaging to delineate any structural lesion that may be maintaining a peripheral drive on central sensitization. Examples include:
a.A poorly healed fracture, a meshoma (herniorrhaphy), entrapment of a peripheral nerve or a neuroma (in scar tissue)
2.Quantitative sensory testing
3.EMG and nerve conduction velocities to evaluate affected nerves
1.A neuroma is a tangled mass of connective tissue in which are imbedded distally sprouting regenerating axons. There are both myelinated and unmyelinated axons in a neuroma
2.Neuromas may form in any tissue in which there is transection of a peripheral nerve
3.They are extremely common following traumatic amputation of a limb and in this instance may cause incapacitating pain in up to 10% of patients
1.Mechanical stimulation of a neuroma may induce minor dysesthesia to extreme pain
2.It is typically a painful or tender nodule
3.Usually they occur post-surgically but may occur following minor trauma
4.If they occur in a nerve plexus multiple neuromas can form
5.They may fire spontaneously and have extremely low mechanical thresholds for discharge. In some instances they are responsive to alpha adrenergic stimuli
6.Scar neuromas may form at any surgical site
7.Neuroma-in-continuity:
a.May cause a dysfunctional nerve:
i.Tinel’s sign (local tenderness over the injured nerve site that causes distal radiating tingling or paresthesia)
ii.Denervation atrophy of the innervated muscles, sensory loss and trophic changes in the territory of the injured nerve
1.Traumatic neuromas are usually bulbous in shape
2.They consist of an unorganized network of connective tissue intermingled with regenerating nerve fibers, Schwann cells, macrophages, fibroblasts and myofibroblasts
3.Myofibroblasts may be a contributor to pain by causing the collagen matrix to contract around nerve fibers. Alpha smooth muscle actin (α-SMA) has been demonstrated in neuromas from patients that caused neuropathic pain
4.Electrophysiological studies demonstrate basal spontaneous discharge which is enhanced by mechanical stimuli that show that neuromas may act as an ectopic generator of action potentials
5.There is experimental support for ephaptic transmission of efferent autonomic fibers to afferent sensory fibers within neuromas
6.Neuroma-in-continuity:
a.Usually involves both myelin, axon and perineurial injury within a scarred nerve. The proximal injured nerve fascicles sprout but are unable to reunite correctly due to lattice disruption, dysfunctional regeneration, hypertrophy of nerve fascicles and fibrosis.
b.Neuromas-in-continuity are divided into two forms:
i.Spindle neuromas with intact perineurium
ii.Lateral neuromas that occur after partial disruption of the perineurium or after nerve repair
c.End-bulb neuromas:
i.May occur in any location; a nerve is completely divided and is unopposed by another neural tissue
ii.They are seen in nerves that have been completely severed and in amputations. They are also encountered in lacerations in which the nerve is not repaired or in post-operative patients in which the nerves have been severed
1.High-resolution ultrasound can distinguish neuromas in injured peripheral nerves
2.MRI:
a.Microneurography utilizing fat-suppressed fluid-sensitive sequences in association with T1-weighted sequences demonstrate changes in nerve size, signal intensity and location
3.MRI in neuropraxia and axonometmesis:
a.Enlarged and T2 hyperintense nerves are demonstrated possibly due to proximally obstructed axoplasmic flow and distal Wallerian degeneration
4.Neuroma-in-continuity:
a.A round mass with nerve continuity on either side (may be similar in appearance to a neurofibroma or Schwannoma)
b.Distinguishing features from nerve sheath tumors are:
i.Surrounding scarring
ii.Lack of a split fat or target sign
iii.Absence of abnormal enhancement
5.End bulb neuroma:
a.Occurs in a completely severed nerve and demonstrates:
i.A T2 sequence nerve that terminates in a round mass that may resemble a balloon on a string or a green onion
ii.MRI of traumatic neuromas:
1.Some are neuromas-in-continuity and others are end-bulb neuromas
2.Mean size is usually 1.5cm (range 0.6 to 4.8cm)
3.Almost all have indistinct margins and may have a capsule
4.Approximately 80% will enhance
5.Most have a tail sign
6.There is a moderate correlation between the size of the affected nerve and the size of the neuroma
1.The amputation of a limb causes an almost immediate experience of phantom sensations in 90 to 98% of patients. Approximately 75% of patients experience the phantom upon awakening from anesthesia and the remaining patients experience phantom sensations within days or weeks
2.Phantom pain is pain in the body part that is no longer present
1.Phantom sensations include:
a.Feeling of the continued presence of the limb
b.Feeling of a specific position, (often twisted), shape (often distorted and too small) or movement of the missing limb
c.Sensations of warmth or cold, itch, tingling or lancinating (electric-like) sensations
d.Sensations related to length and volume or that the phantom is behaving as the normal limb
e.A feeling that the phantom limb is gradually shortening which is defined as “telescoping”
f.In most patients that experience innocuous sensations also report pain
g.Phantom pain:
i.May be related to a specific position or movement of the phantom
ii.The pain may be exacerbated by changes in the barometric pressure, stress (emotional) and mechanical stimuli
iii.The pain is more severe in the distal portion of the phantom
iv.The quality of the pain includes:
1.Stabbing
2.Throbbing
3.Burning
4.Cramping
5.An unusual distorted posture
6.Squeezing
v.Phantom body pain occurs with spinal cord injury
vi.Phantom pain is less frequent if the amputation occurs at a very young age. Older children have an adult pattern of pain
vii.Phantom sensations occur in patients with congenital absence of a limb but pain under this circumstance is very rare
viii.The stump of the amputated extremity may demonstrate mechanical allodynia particularly adjacent to the skin flap scar or near neuromas
ix.Exacerbation of both painful and non-painful sensations by emotional stimuli, micturition or yawning
x.Exacerbation of both painful and non-painful phantom limb sensations by noxious or innocuous stimuli at the stump or from distal body areas
1.There is a correlation between pain in the residual stump and phantom limb pain
2.Ectopic discharge from stump neuromas are a component of the nociceptive input to the pain matrix
3.The rapid onset of phantom pain may be initiated from end bulbs of the severed nerves prior to the formation of neuromas
4.Another site of ectopic discharge following amputation is the dorsal root ganglia (DRG); ectopia here can also summate with that from neuromas in the residual stump
5.As noted earlier, increased sympathetic discharge and circulating epinephrine can exacerbate ectopic firing of neuromas (sympathetic – sensory coupling). This phenomena can occur both at the level of the neuroma and the DRG
6.Decreased near-surface blood flow to the skin has been suggested as predictive of burning phantom limb pain
7.Cramping and squeezing descriptions of phantom pain have been associated with muscle tension in the residual stump
8.Sympathetic-efferent and somatic-afferent mechanisms appear to be a component of a peripheral mechanism of phantom pain
9.Central mechanisms of phantom pain:
a.Central sensitization at the spinal level of pain projecting neurons and at other levels of the pain matrix has been demonstrated experimentally:
i.A major component of this sensitization is due to increased efficacy of transmission of NMDA receptors to glutamate
ii.As part of central sensitization, mechanoreceptive A-beta fibers have input to the ascending pain projecting system. In neuropathic conditions, this may be a mechanism of mechanohyperalgesia and allodynia. In the instance of phantom pain, low threshold mechano afferents may contribute to hyperexcitability and ectopic discharge of dorsal horn pain projecting neurons. Although controversial, it has been demonstrated that nociceptive afferents may degenerate and vacate lamina I of the dorsal horn. Deeper synapsing low-threshold afferents of lamina III-IV may sprout and synapse with the deafferented pain projecting neurons in lamina I
10. Other putative mechanisms that have been postulated to contribute to phantom pain:
a.Down-regulation of opioid receptors in primary nociceptive afferents and intrinsic spinal neurons in addition to reduced GABAergic and glycinergic inhibition
b.There is a phenotypic switch in which substance P is secreted by A-beta low threshold mechano afferents that renders them similar to nociceptors. Substance P is the ligand for NK1 receptors on lamina I pain projecting nociceptive neurons
c.In injured tissue, cholecystokinin, an endogenous inhibitor of the mu opioid receptor is upregulated
d.At the spinal cord level, descending inhibition from supraspinal levels may be lost as well as that from local intersegmental inhibitory mechanisms
e.Brain level changes with phantom pain:
i.Cortical reorganization occurs in which the cortical representation of the amputated extremity is annexed by neighboring representational zones in both the primary somatosensory and motor cortex. This is the operational definition of maladaptive plasticity in which afferented areas enlarge or shift their activation into somatotopically deafferented brain areas. In some instances, the greater the shift the more severe the pain. There are inconsistencies with this construct as a mirror movement task has demonstrated reduced activity in patients with phantom pain (in the deafferented areas) which was correlated with decreased pain severity. In addition, other cortical brain areas including the supplementary motor cortex may be incorporated into maladaptive plasticity
1.Ultrasound and MRI to identify stump neuromas that may contribute to the peripheral maintenance of phantom pain
Activated microglia have altered expression of genes that upregulate cell-surface receptors (P2X4R being primary) and intracellular signaling molecules (p38 MAPK as primary) that produce and secrete diffusible factors that include BDNF and proinflammatory cytokines that modulate pain processing in the dorsal horn of the spinal cord.