ASSIGNMENT: PHARMACOTHERAPEUTICS III
NEURALGIAS
Submitted By: Lahari Paladugu (Roll No. 11 PharmD 09-10)
Submitted To: Theenarasu Sir
Submitted On: 10/18/2012
DEFINITION
Neuralgia is pain in one or more nerves caused by a change in neurological structure or function
of the nerve/s rather than by excitation of healthy pain receptors. Neuralgia falls into two
categories: central neuralgia, where the cause of the pain is located in the spinal cord or brain,
and peripheral neuralgia. This unusual pain is thought to be linked to four possible mechanisms:
ion channel gate malfunctions; the nerve fibers become mechanically sensitive and create an
ectopic signal; signals in touch fibers cross to pain fibers; and malfunction due to damage in the
brain and spinal cord.
CLASSIFICATION
Neuralgias can be classified into 3 categories:
(1)
(2)
(3)
(4)
Atypical (Trigeminal) Neuralgia
Glossopharyngeal Neuralgia
Occipital Neuralgia
Postherpetic Neuralgia
(1) Atypical (trigeminal) Neuralgia
Atypical trigeminal neuralgia (ATN) is a rare form of neuralgia and may also be the most
misdiagnosed form. The symptoms can be mistaken for migraines, dental problems such as
temporomandibular joint disorder, musculoskeletal issues, and hypochondriasis. ATN can have
a wide range of symptoms and the pain can fluctuate in intensity from mild aching to a crushing
or burning sensation, and also to the extreme pain experienced with the more common
trigeminal neuralgia. ATN pain can be described as heavy, aching, and burning. Sufferers have a
constant migraine-like headache and experience pain in all three trigeminal nerve branches.
This includes aching teeth, ear aches, feeling of fullness in sinuses, cheek pain, pain in forehead
and temples, jaw pain, pain around eyes, and occasional electric shock-like stabs. Unlike typical
neuralgia, this form can also cause pain in the back of the scalp and neck. Pain tends to worsen
with talking, facial expressions, chewing, and certain sensations such as a cool breeze. Vascular
compression of the trigeminal nerve, infections of the teeth or sinuses, physical trauma, or past
viral infections are possible causes of ATN.
(2) Glossopharyngeal Neuralgia
Glossopharyngeal neuralgia consists of recurring attacks of severe pain in the back of the
throat, the area near the tonsils, the back of the tongue, and part of the ear. The pain is due to
malfunction of the glossopharyngeal nerve (CN IX), which moves the muscles of the throat and
carries information from the throat, tonsils, and tongue to the brain.
Glossopharyngeal neuralgia, a rare disorder, usually begins after age 40 and occurs more often
in men. Often, its cause is unknown. However, glossopharyngeal neuralgia sometimes results
from an abnormally positioned artery that compresses the glossopharyngeal nerve near where
it exits the brain stem. Rarely, the cause is a tumor in the brain or neck.
(3) Occipital Neuralgia
Occipital neuralgia, also known as C2 neuralgia, or Arnold's neuralgia, is a medical condition
characterized by chronic pain in the upper neck, back of the head and behind the eyes
(4) Postherpetic Neuralgia
Postherpetic neuralgia (PHN) is a nerve pain due to damage caused by the varicella zoster virus.
Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of
herpes zoster (HZ, commonly known as shingles) in that same dermatomic area. The neuralgia
typically begins when the HZ vesicles have crusted over and begun to heal, but it can begin in
the absence of HZ, in which case zoster sine herpete is presumed
GENERAL PATHOPHYSIOLOGY
Peripheral nerve injury
A neuron’s response to trauma can often be determined by the severity of the injury, classified
by Seddon's classification. In Seddon’s Classification, nerve injury is described as either
neurapraxia, axonotmesis, or neurotmesis. Following trauma to the nerve, a short onset of
afferent impulses, termed “injury discharge”, occurs. While lasting only minutes, this
occurrence has been linked to the onset of neuropathic pain.[2]
When an axon is severed, the segment of the axon distal to the cut degenerates and is
absorbed by Schwann cells. The proximal segment fuses, retracts, and swells, forming a
“retraction bulb.” The synaptic terminal function is lost, as axoplasmic transport ceases and no
neurotransmitters are created. The nucleus of the damaged axon undergoes chromatolysis in
preparation for axon regeneration. Schwann cells in the distal stump of the nerve and basal
lamina components secreted by Schwann cells guide and help stimulate regeneration. The
regenerating axon must make connections with the appropriate receptors in order to make an
effective regeneration. If proper connections to the appropriate receptors are not established,
aberrant reinnervation may occur. If the regenerating axon is halted by damaged tissue,
neurofibrils may create a mass known as a neuroma.[2]
In the event that an injured neuron degenerates or does not regenerate properly, the neuron
loses its function or may not function properly. Neuron trauma is not an isolated event and may
cause degenerative changes in surrounding neurons. When one or more neurons lose their
function or begin to malfunction, abnormal signals sent to the brain may be translated as
painful signals.[2]
Central neuronal injury
Neuronal injury in the central nervous system (CNS) typically leads to local degeneration of the
nerve axon and myelin sheath. Axonal debris in the CNS is eliminated by macrophages. Trauma
to neurons in the CNS also causes a proliferation of glial cells that form a glial scar.
Development of the glial scar is thought to inhibit regeneration of central neural
connections.[citation needed] The damaged nerve terminal begins to swell and glial cells push the
defective terminal away from connections to other neurons.[2] Often, aberrant sprouting of
damaged CNS neurons, specifically sensory neurons, results in neuralgia.
TRIGEMINAL NEURALGIA
Trigeminal neuralgia is a chronic pain condition that affects the trigeminal nerve, which carries
sensation from your face to your brain.
Although neurologic examination findings are normal in patients with the idiopathic variety, the
most common type of facial pain neuralgia, the clinical history is distinctive. Trigeminal
neuralgia is characterized by unilateral pain following the sensory distribution of cranial nerve
V—typically radiating to the maxillary (V2) or mandibular (V3) area in 35% of affected patients often accompanied by a brief facial spasm or tic. Isolated involvement of the ophthalmic
division is much less common.
ETIOLOGY
Although a questionable family clustering exists, trigeminal neuralgia (TN) is most likely is
multifactorial.
Most cases of trigeminal neuralgia are idiopathic, but compression of the trigeminal roots by
tumors or vascular anomalies may cause similar pain
Trigeminal neuralgia is divided into 2 categories, classic and symptomatic.
 The classic form, considered idiopathic, actually includes the cases that are due to a
normal artery present in contact with the nerve, such as the superior cerebellar artery
or even a primitive trigeminal artery.
 Symptomatic forms can have multiple origins. Aneurysms, tumors, chronic meningeal
inflammation, or other lesions may irritate trigeminal nerve roots along the pons
causing symptomatic trigeminal neuralgia. An abnormal vascular course of the superior
cerebellar artery is often cited as the cause. Uncommonly, an area of demyelination
from multiple sclerosis may be the precipitant (see the following image); lesions in the
pons at the root entry zone of the trigeminal fibers have been demonstrated. These
lesions may cause a similar pain syndrome as in trigeminal neuralgia.
Tumor-related causes of trigeminal neuralgia (most commonly in the cerebello-pontine angle)
include acoustic neurinoma, chordoma at the level of the clivus, pontine glioma or
glioblastoma, epidermoid, metastases, and lymphoma. Trigeminal neuralgia may result from
paraneoplastic etiologies.
Vascular causes include a pontine infarct and arteriovenous malformation or aneurysm in the
vicinity.
Inflammatory causes include multiple sclerosis (common), sarcoidosis, and Lyme disease
neuropathy.
Infrequently, adjacent dental fillings composed of dissimilar metals may trigger attacks, and one
atypical case followed tongue piercing. Another case report of trigeminal neuralgia was
reported in a patient with spontaneous intracranial hypotension; both conditions resolved
following surgical treatment of a cervical root sleeve dural defect.
Triggers
A variety of triggers may set off the pain of trigeminal neuralgia, including:
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Shaving
Stroking your face
Eating
Drinking
Brushing your teeth
Talking
Putting on makeup
Encountering a breeze
Smiling
Washing your face
PATHOPHYSIOLOGY
Neuropathic pain is the cardinal sign of injury to the small unmyelinated and thinly myelinated
primary afferent fibers that subserve nociception. The pain mechanisms themselves are
altered. Microanatomic small and large fiber damage in the nerve, essentially demyelination,
commonly observed at its root entry zone (REZ), leads to ephaptic transmission, in which action
potentials jump from one fiber to another. A lack of inhibitory inputs from large myelinated
nerve fibers plays a role. Additionally, a reentry mechanism causes an amplification of sensory
inputs. However, features also suggest an additional central mechanism (eg, delay between
stimulation and pain, refractory period).
CLINICAL SINGS & SYMPTOMS
Patients can localize their pain precisely. The pain is not confined exclusively to 1 of the 3
divisions of the trigeminal nerve but more commonly runs along the line dividing either the
mandibular and maxillary nerves or the mandibular and ophthalmic portions of the nerve.
Trigeminal neuralgia symptoms may include one or more of these patterns:
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Occasional twinges of mild pain
Episodes of severe, shooting or jabbing pain that may feel like an electric shock
Spontaneous attacks of pain or attacks triggered by things such as touching the face,
chewing, speaking and brushing teeth
Bouts of pain lasting from a few seconds to several seconds
Episodes of several attacks lasting days, weeks, months or longer — some people have
periods when they experience no pain
Pain in areas supplied by the trigeminal nerve, including the cheek, jaw, teeth, gums,
lips, or less often the eye and forehead
Pain affecting one side of the face at a time
Pain focused in one spot or spread in a wider pattern
Attacks becoming more frequent and intense over time
The pain quality is characteristically severe, paroxysmal, and lancinating. It commences with a
sensation of electrical shocks in an affected area, then quickly crescendos in less than 20
seconds to an excruciating discomfort felt deep in the face, often contorting the patient's
expression. The pain then begins to fade within seconds, only to give way to a burning ache
lasting seconds to minutes. During attacks, patients may grimace, wince, or make an aversive
head movement, as if trying to escape the pain, thus producing an obvious movement, or tic;
hence the term "tic douloureux."
This condition is an exception to the rule that nerve injuries typically produce symptoms of
constant pain and allodynia. If the pain is particularly frequent, patients may be difficult to
examine during the height of an attack. The number of attacks may vary from less than 1 per
day, to a 12 or more per hour, up to hundreds per day. Outbursts fully abate between attacks,
even when they are severe and frequent.
CLASSIFICATION
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Trigeminal neuralgia type 1 (TN1): The classic form of trigeminal neuralgia in which
episodic lancinating pain predominates
Trigeminal neuralgia type 2 (TN2): The atypical form of trigeminal neuralgia in which
more constant pains (aching, throbbing, burning) predominate
Trigeminal neuropathic pain (TNP): Pain that results from incidental or accidental injury
to the trigeminal nerve or the brain pathways of the trigeminal system
Trigeminal deafferentation pain (TDP): Pain that results from intentional injury to the
system in an attempt to treat trigeminal neuralgia (Numbness of the face is a constant
part of this syndrome, which has also been referred to as anesthesia dolorosa or one of
its variants.)
Symptomatic trigeminal neuralgia (STN): Trigeminal neuralgia associated with multiple
sclerosis (MS)
Postherpetic neuralgia (PHN): Chronic facial pain that results from an outbreak of
herpes zoster (shingles), usually in the ophthalmic division (V1) of the trigeminal nerve
on the face and usually in elderly patients
 Geniculate neuralgia (GeN): Pain typified as episodic and lancinating, felt deep in the ear
 Glossopharyngeal neuralgia (GPN): Pain typified in the tonsillar area or throat, usually
triggered by talking or swallowing

LABORATORY INVESTIGATIONS
No laboratory, electrophysiologic, or radiologic testing is routinely indicated for the diagnosis of
trigeminal neuralgia (TN), as patients with characteristic history and normal neurologic
examination may be treated without further workup.
The diagnosis of facial pain is almost entirely based on the patient's history. In most cases of
facial pain, no specific laboratory tests are needed. A blood count and liver function tests are
required if therapy with carbamazepine is contemplated. Oxcarbazepine can cause
hyponatremia, so the serum sodium should be tested after institution of therapy.
In cases with suspected metastatic carcinomatosis, cerebrospinal fluid analysis may confirm the
diagnosis. When surgical procedures are contemplated, appropriate and routine preoperative
laboratory tests are in order.
In patients older than 60 years, the clinician may first choose to assess the response to a
therapeutic trial of medication before considering imaging. A clear relief of pain with
carbamazepine or another anticonvulsant confirms the diagnosis of idiopathic trigeminal
neuralgia.
Imaging studies are indicated, because distinguishing between classic and symptomatic forms
of trigeminal neuralgia is not always clear. Approximately 15% of patients with trigeminal
neuralgia (any form) have abnormalities on neuroimaging (computed tomography [CT] scanning
and/or magnetic resonance imaging [MRI]). The most common findings are cerebello-pontine
angle tumors and multiple sclerosis.
TREATMENT
Treatment can be subdivided into pharmacologic therapy, percutaneous procedures, surgery,
and radiation therapy. Adequate pharmacologic trials should always precede the contemplation
of a more invasive approach.
Carbamazepine remains the criterion standard, but a number of other drugs have been used for
a long time and with fair success in trigeminal neuralgia.
1) Anticonvulsant agents
 Drugs: Carbamazepine, Gabapentin, Lamotrigine, Phenytoin, Topiramate,
Oxcarbazepine
 Action: Anticonvulsant drugs reduce the excitability of gasserian ganglion
neurons, preventing anomalous discharges and related lancinating
volleys of pain. Thus, these agents may help control paroxysmal pain by
limiting the aberrant transmission of nerve impulses and reducing the
firing of nerve potentials in the trigeminal nerve.
2) Skeletal Muscle Relaxants
 Drugs: Baclofen
 Action: Several small, uncontrolled studies in the 1970s and 1980s,
including those by Parekh et al and Fromm et al, demonstrated
effectiveness of baclofen, particularly when added to an existing regimen
of carbamazepine that is not providing adequate pain control. Once
baclofen is added to an anticonvulsant, the dosage of the anticonvulsant
often can be reduced.
3) Tricyclic Antidepressants
 Drugs: Amitriptyline
 Action: Tricyclic antidepressants are a complex group of drugs that have
central and peripheral anticholinergic effects, as well as sedative effects.
They have central effects on pain transmission and block the active
reuptake of norepinephrine and serotonin.
4) Toxins
Drugs: Botulinum Toxin
 Action: Toxins are a relatively recent experimental approach to
management of trigeminal neuralgia and have been mentioned to
respond to patient inquiries. These agents are not recommended
because of scant evidence of efficacy. The mechanism of action of these
agents remains unclear, but they appear to potentially decrease painful
afferents. Subcutaneous injections of botulinum toxin have been
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beneficial in a pilot study of patients with ophthalmologic manifestations
of trigeminal neuralgia.
SURGICAL CONSIDERATIONS
Over time, the drugs used for the treatment of trigeminal neuralgia often lose effectiveness as
patients experience breakthrough pain. For patients in whom medical therapy has failed,
surgery is a viable and effective option.
Three operative strategies now prevail: percutaneous procedures, gamma knife surgery (GSK),
and microvascular decompression (MVD).
PATIENT EDUCATION
Patients benefit from an explanation of the natural history of the disorder, including the
possibility that the syndrome may remit spontaneously for months or even years before they
need to consider long-term anticonvulsant medications. For this reason, some may elect to
taper off their medication after the initial attack subsides; thus, they should be educated about
the importance of being compliant with their medication regimen.
Patients also must be educated about the potential risks of anticonvulsant medications, such as
sedation and ataxia, particularly in elderly patients, which may make driving or operating
machinery hazardous. These drugs may also pose risks to the liver and the hematologic system.
Document the discussion with the patient about these potential risks.
No specific preventative therapy exists. Patients may have a premonitory atypical pain for
months; therefore, appropriate recognition of this pre–trigeminal neuralgia syndrome may lead
to earlier and more efficient treatment.
Patients should avoid maneuvers that trigger pain. Once the diagnosis is established, advise
them that dental extractions do not afford relief, even if pain radiates into the gums.
In patients wishing to undergo a procedure, they should be aware of potential adverse effects,
as well as report any altered sensation in the face, especially after a procedure. They should be
informed about the potential for anesthesia dolorosa.
GLOSSOPHYRANGEAL NEURALGIA
Glossopharyngeal neuralgia is a condition in which there are repeated episodes of severe pain
in the tongue, throat, ear, and tonsils, which can last from a few seconds to a few minutes.
ETIOLOGY/PATHOPHYSIOLOGY
Glossopharyngeal neuralgia is believed to be caused by irritation of the ninth cranial nerve,
called the glossopharyngeal nerve. Symptoms usually begin in people over age 40.
In most cases, the source of irritation is never found. Some possible causes for this type of
nerve pain (neuralgia) are:
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Blood vessels pressing on the glossopharyngeal nerve
Growths at the base of the skull pressing on the glossopharyngeal nerve
Tumors or infections of the throat and mouth pressing on the glossopharyngeal nerve
CLINICAL SINGS & SYMPTOMS
Symptoms include severe pain in areas connected to the ninth cranial nerve:
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Back of the nose and throat (nasopharynx)
Back of the tongue
Ear
Throat
Tonsil area
Voice box (larynx)
The pain occurs in episodes and may be severe. It is usually on one side, and feels jabbing. The
episodes can occur many times each day, and awaken the person from sleep.
It can sometimes be triggered by:
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Chewing
Coughing
Laughing
Speaking
Swallowing
LABORATORY INVESTIGATIONS
Tests will be done to identify problems, such as tumors, at the base of the skull. Tests may
include:
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Blood tests (sugar level) to look for the causes of nerve damage
CT scan of the head
MRI of the head
X-rays of the head or neck
Sometimes the MRI may show swelling (inflammation) of the glossopharyngeal nerve.
To find out whether a blood vessel is pressing on the nerve, pictures of the brain arteries may
be taken using:
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Magnetic resonance angiography (MRA)
CT angiogram
X-rays of the arteries with a dye (conventional angiography)
PHARMACOTHERAPY
The goal of treatment is to control pain. Over-the-counter painkillers such as aspirin and
acetaminophen are not very effective for relieving glossopharyngeal neuralgia.
The most effective drugs are antiseizure medications, such as carbamazepine, gabapentin,
pregabalin, and phenytoin. Some antidepressants, such as amitriptyline or nortriptyline, may
help certain people.
Initial treatment of Glossopharyngeal Neuralgia is medical with carbamazepine and gabapentin
being the medications of choice. Unfortunately, these medications are not as effective for
Glossopharyngeal Neuralgia as they are for Trigeminal Neuralgia. As a result, the majority of
patients require Microvascular Ddecompression (MVD) which is the only advisable surgical
procedure.
OCCIPITAL NEURALGIA
Occipital neuralgia is a neurological condition in which the occipital nerves -- the nerves that
run from the top of the spinal cord at the base of the neck up through the scalp -- are inflamed
or injured. Occipital neuralgia can be confused with a migraine, or other types of headache,
because the symptoms can be similar. But occipital neuralgia is a distinct disorder that requires
an accurate diagnosis to be treated properly.
ETIOLOGY
Patients with occipital neuralgia may be divided into those with structural causes and those
with idiopathic causes. Structural causes include:
 trauma to the greater and/or lesser occipital nerves
 compression of the greater and/or lesser occipital nerves or C2 and/or C3 nerve
roots by
 degenerative cervical spine changes
 cervical disc disease
 tumors affecting the C2 and C3 nerve roots.
Occipital neuralgia is the result of compression or irritation of the occipital nerves due to injury,
entrapment of the nerves, or inflammation. Many times, no cause is found.
There are many medical conditions that are associated with occipital neuralgia, including:
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Trauma to the back of the head
Neck tension and/or tight neck muscles
Osteoarthritis
Tumors in the neck
Cervical disc disease
Infection
Gout
Diabetes
Blood vessel inflammation
PATHOPHYSIOLOGY
Occipital neuralgia is caused by damage to these nerves. Ways in which they can be damaged
include trauma (usually concussive), physical stress on the nerve, repetitious neck contraction,
flexion or extension, and as a result of medical complications (such as osteochondroma, a
benign tumour of the bone).
The greater occipital nerve receives sensory fibers from the C2 nerve root and the lesser
occipital nerve receives fibers from the C2 and C3 nerve roots. The third occipital nerve (least
occipital nerve) stems from the medial sensory branch of the posterior division of the C3 nerve
root and travels along the greater occipital nerve. It passes through the trapezius and splenius
capitus slightly medial to the greater occipital nerve. Clinically, the third occipital nerve may
also be involved in causing occipital neuralgia. Cervical spine changes include spondylosis,
arthritis of the upper cervical facet joints, and thickening of the ligaments in that area
(particularly C1-4 levels). Some cases of presumed occipital neuralgia may in fact be C2 or
C3 radiculopathies. Compression of the greater occipital nerve is possible as it travels up the
neck, passing through the semispinalis and trapezius muscles. Whiplash or hyperextension
injury may lead to this scenario. Other possible causes include localized infections or
inflammation, gout, diabetes, and blood vessel inflammation. Although it cannot be quantified,
most patients fall in the category of “unknown cause,” when no identifiable lesion is found.
One cause is vascular compression.
CLINICAL SINGS & SYMPTOMS
Occipital neuralgia can cause very intense pain that feels like a sharp, jabbing, electric shock in
the back of the head and neck. Other symptoms of occipital neuralgia may include:
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Aching, burning, and throbbing pain that typically starts at the base of the head and
radiates to the scalp
Pain on one or both sides of the head
Pain behind the eye
Sensitivity to light
Tender scalp
Pain when moving the neck
LABORATORY INVESTIGATIONS
Local anesthetic block of the occipital nerves, either peripherally or more proximally at the C2
and/or C3 nerve root, may aid in diagnosis.
PHARMACOTHERAPY
Treatment depends on what is causing the inflammation or irritation of the occipital nerves.
The first course of action is to relieve pain.
If the cause is structural, then surgical treatment may be indicated. Because the majority of
patients have no clear structural cause, their treatment is usually symptomatic. Local nerve
blocks, medications, occipital nerve stimulator implantation, surgical decompression, or
lesioning of the C2 and/or C3 nerve roots, or even the greater and/or lesser occipital nerves,
may be considered.
Occipital neuralgia is often difficult to manage because it can easily be mistaken for other
headache syndromes. Management of occipital neuralgia follows the usual course, starting with
the recommended conservative treatment, conventional therapy, and medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), neuropathic medications (seizure medications,
tricyclic antidepressants), and possibly opioids.
Medications that may help relieve pain in occipital neuralgia include:
 gabapentin 300-3600 mg/day
 carbamazepine 400-1200 mg/day
 phenytoin 300-600 mg/day
 valproic acid 500-2000 mg/day
 baclofen 40-120 mg/day
 NSAIDs and opioids may also be beneficial
Physical therapy, massage, acupuncture, and heat are other treatments that can be used for
the treatment of occipital neuralgia.
Surgery may be considered if pain does not respond to other treatments or comes back.
Surgery may include:
Microvascular decompression. During this procedure, your doctor may be able to relieve
pain by identifying and adjusting blood vessels that may be compressing the nerve.
 Occipital nerve stimulation. In this procedure, a neurostimulator is used to deliver
electrical impulses to the occipital nerves. These electrical impulses can help block pain
messages to the brain.
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Radiofrequency thermocoagulation (RF) is another widely used method to treat occipital
neuralgia. It has many advantages, including safety, efficacy, a rapid recovery period, and no
permanent scarring.
Pulsed radiofrequency (PRF) is yet another technique used to treat occipital neuralgia.
POSTHERPETIC NEURALGIA
Herpes zoster (HZ) is a viral infection that usually presents as a childhood infection of varicella
(ie, chicken pox). The pathogen is human herpesvirus-3 (HHV-3), also known as the varicella
zoster virus (VZV). Following the acute phase, the virus enters the sensory nervous system,
where it is harbored in the geniculate, trigeminal, or dorsal root ganglia and remains dormant
for many years. With advancing age or immune-compromised states, the virus reactivates and
an eruption (ie, shingles) occurs. Even after the acute rash subsides, pain can persist or recur in
shingles-affected areas. This condition is known as postherpetic neuralgia (PHN).
ETIOLOGY
 Risk factors for development of PHN include the following:
 Advancing age
 Site of HZ involvement
o Lower risk - Jaw, neck, sacral, and lumbar
o Moderate risk - Thoracic
o Highest risk - Trigeminal (especially ophthalmic division), brachial plexus
 Severe prodromal pain (with HZ)
 Severe rash
PATHOPHYSIOLOGY
Some patients with postherpetic neuralgia (PHN) appear to have abnormal function of
unmyelinated nociceptors and sensory loss (usually minimal). Pain and temperature detection
systems are hypersensitive to light mechanical stimulation, leading to severe pain (allodynia).
Allodynia may be related to formation of new connections involving central pain transmission
neurons. Other patients with PHN may have severe, spontaneous pain without allodynia,
possibly secondary to increased spontaneous activity in deafferented central neurons or
reorganization of central connections. An imbalance involving loss of large inhibitory fibers and
an intact or increased number of small excitatory fibers has been suggested. This input on an
abnormal dorsal horn containing deafferented hypersensitive neurons supports the clinical
observation that both central and peripheral areas are involved in the production of pain.
Although HZ symptoms may be confined to a few sensory dermatomes, pathological changes
may be more widespread. Affected ganglia of the spinal or cranial nerve roots are swollen and
inflamed with a primarily lymphocytic reaction. Some ganglion cells are swollen while others
are degenerated.
Inflammation extends into the meninges and root entry zone and may be present in the ventral
horn and perivascular space of the spinal cord. Pathological changes in the brain stem are
similar to those in the spinal root and spinal cord. In the months following infection, fibrosis
occurs in the ganglia, peripheral nerve, and nerve root. Degeneration occurs in the ipsilateral
posterior column.
CLINICAL SINGS & SYMPTOMS
 A painful vesicular eruption in a dermatomal distribution is typical of herpes zoster (HZ).
 With resolution of the eruption, pain that continues for 3 months or more is defined as
postherpetic neuralgia (PHN).
 Pain is intense and may be described as burning, stabbing, or gnawing.
 Area of previous HZ may show evidence of cutaneous scarring.
 Sensation may be altered over involved areas, in the form of either hypersensitivity or
decreased sensation.
 Allodynia is pain produced by a non-noxious stimulus, such as a light touch by a brush,
and may be present over the involved area.
 Changes in autonomic function such as increased sweating over the involved area may
be seen.
LABORATORY INVESTIGATIONS
 No laboratory work is usually necessary in cases of postherpetic neuralgia (PHN).
 Results of cerebrospinal fluid (CSF) evaluation are abnormal in 61%.
o Pleocytosis is observed in 46%, elevated protein in 26%, and varicella zoster virus
(VZV) DNA in 22%.
o These findings are not predictive of the PHN clinical course.
 Viral culture or immunofluorescent staining may be used to differentiate herpes simplex
from herpes zoster in cases that are difficult to distinguish clinically.
 Antibodies to herpes zoster can be measured. A 4-fold increase has been used to
support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a
rising titer secondary to viral exposure rather than reactivation cannot be ruled out.
PHARMACOTHERAPY
The goal of therapy for postherpetic neuralgia (PHN) is to reduce morbidity through the use of
tricyclic antidepressants, anticonvulsants, anesthetics, analgesics, corticosteroids, and antiviral
agents.
1) Tricyclic Antidepressants
 Drugs: Amitryptilline, Nortryptilline
 Action: Complex group of drugs that have central and peripheral anticholinergic
effects as well as sedative effects. They have central effects on pain
transmission. They block the active reuptake of norepinephrine and serotonin.
2) Analgesics
 Drugs: Capsaicin (transdermal patch or topical)
 Action: By depleting and preventing reaccumulation of substance P in peripheral
sensory neurons, may render skin and joints insensitive to pain. Substance P
thought to be chemomediator of pain transmission from periphery to CNS.
Transient receptor potential vanilloid-1 (TRPV1) agonist indicated for
neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion
channel–receptor complex expressed on nociceptive skin nerve fibers. Topical
capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain
relief by reduction in TRPV1-expressing nociceptive nerve endings.
3) Corticosteroids
 Drugs: Dexamethasone, Prednisone, Methylprednisolone
 Action: Decreases inflammation by suppressing migration of polymorphonuclear
leukocytes and by reversing increased capillary permeability.
4) Antiviral Agents
 Drugs: Famciclovir
 Action: Pro-drug that, when biotransformed into active metabolite penciclovir,
may inhibit viral DNA synthesis/replication.
5) Anaesthetics
 Drugs: Lidocaine
 Action: These agents stabilize the neuronal membrane so the neuron is less
permeable to ions. This prevents the initiation and transmission of nerve
impulses, thereby producing the local anesthetic action.
6) Anticonvulsants
 Drugs: Pregabalin, Gabapentin, Gabapentin enecarbil
 Action: These agents are used to manage severe muscle spasms and provide
sedation in neuralgia. They have central effects on pain modulation.
7) Vaccines
 Drugs: Zoster vaccine live (Zostavax)
 Action: Used for prevention of HZ outbreak.
 ADRS:
NON-PHARMACOLOGICAL TREATMENT
Other non-pharmacological treatments for postherpetic neuralgia include the following:
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Relaxation techniques. These can include breathing exercises, visualization and
distraction.
Heat therapy.
Cold therapy. Cold packs can be used.
Transcutaneous Electrical Nerve Stimulation (TENS). This involves the stimulation of
peripheral nerve endings by the delivery of electrical energy through the surface of the
skin.
Spinal cord stimulator. The electrical stimulation of the posterior spinal cord works by
activating supraspinal and spinal inhibitory pain mechanisms.
REFERENCES
1. http://www.webmd.com/migraines-headaches/occipital-neuralgia-symptoms-causestreatments
2. http://en.wikipedia.org/wiki/Occipital_neuralgia
3. http://emedicine.medscape.com/article/1143066-overview#showall
4. http://emedicine.medscape.com/article/1143066-clinical#showall
5. http://emedicine.medscape.com/article/1143066-differential
6. http://emedicine.medscape.com/article/1143066-workup#showall
7. http://emedicine.medscape.com/article/1143066-treatment#showall
8. http://emedicine.medscape.com/article/1143066-medication#showall
9. http://emedicine.medscape.com/article/1143066-followup#showall
10. http://www.pain-consultant.co.uk/pdf/Occipitalneuralgia.pdf
11. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002602/
12. http://www.pain-consultant.co.uk/pdf/Occipitalneuralgia.pdf
13. http://www.mayoclinic.com/health/trigeminal-neuralgia/DS00446
14. http://www.mayoclinic.com/health/trigeminalneuralgia/DS00446/DSECTION=symptoms
15. http://www.mayoclinic.com/health/trigeminal-neuralgia/DS00446/DSECTION=causes
16. http://www.mayoclinic.com/health/trigeminalneuralgia/DS00446/DSECTION=treatments-and-drugs
17. http://www.mayoclinic.com/health/trigeminalneuralgia/DS00446/DSECTION=alternative-medicine
18. http://emedicine.medscape.com/article/1145144-clinical#showall
19. http://emedicine.medscape.com/article/1145144-overview#showall
20. http://emedicine.medscape.com/article/1145144-differential
21. http://emedicine.medscape.com/article/1145144-workup#showall
22. http://emedicine.medscape.com/article/1145144-treatment#showall
23. http://emedicine.medscape.com/article/1145144-medication#showall
24. http://en.wikipedia.org/wiki/Trigeminal_neuralgia