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) Atypical (Trigeminal) Neuralgia(2) Glossopharyngeal Neuralgia(3) Occipital Neuralgia(4) 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:

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:

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

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

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:

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:

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:

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:

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:

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 thosewith 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:

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 lesseroccipital nerve receives fibers from the C2 and C3 nerve roots. The third occipital nerve (leastoccipital 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 orC3 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:

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, orlesioning 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 non-steroidal 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.

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 lumbaro Moderate risk - Thoracico 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:

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-causes-treatments

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