Postherpetic neuralgia

Postherpetic neuralgia (PHN) is a painful condition caused by the varicella zoster virus in a dermatomal distribution (the area governed by a particular sensory nerve) after an attack of herpes zoster (HZ) (commonly known as shingles), usually manifesting after the vesicles have crusted over and begun to heal.

There are a number of treatment options for PHN including antidepressants, anticonvulsants (such as gabapentin or pregabalin) and topical agents such as lidocaine patches or capsaicin lotion. Opioid analgesics may also be appropriate in many situations. There are some sporadically successful experimental treatments, such as rhizotomy (severing or damaging the affected nerve to relieve pain), and TENS (a type of electrical pulse therapy).

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Pathophysiology

Postherpetic neuralgia is thought to result after nerve fibers are damaged during a case of Herpes Zoster (also known as Shingles). Damaged fibers cannot send electrical signals from the skin to the brain as they normally do, and may be erratic or exaggerated, causing chronic, often excruciating pain that may persist or recur for months — or even years — in the area where shingles first occurred.

Frequency

Each year, approximately 1,000,000 individuals in the United States develop shingles, or herpes zoster. Approximately 20 percent of these shingles patients, or 200,000 individuals, go on to suffer from PHN, or post-herpetic neuralgia.

Predisposing factors

• Race: It may influence susceptibility to herpes zoster. African Americans are one fourth as likely as Caucasians to develop this condition.

Signs and symptoms

Symptoms:

• With resolution of the HZ eruption, pain that continues for 3 months or more is defined as PHN.
• Pain is variable from discomfort to very severe and may be described as burning, stabbing, or gnawing.

Signs:

• 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.
• In rare cases, the patient might also experience muscle weakness, tremor or paralysis — if the nerves involved also control muscle movement.

When to seek medical advice

It is strongly recommended by professionals that patients see a doctor at the first sign of shingles. Treating shingles early — within three days of developing the rash — and aggressively with oral antiviral drugs may reduce the length and severity of postherpetic neuralgia. In addition, amitriptyline may reduce the risk of developing PHN.^[1]

If patients do develop postherpetic neuralgia, they are also advised to see their doctor immediately. They may have to work with their doctor and sometimes other specialists such as neurologists to try a variety of treatments before they find something that helps.

Lab and imaging studies

Lab Studies:

• No laboratory work is usually necessary.
• Results of cerebrospinal fluid (CSF) evaluation are abnormal in 61%.
  • Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%.
• These findings are not predictive of the PHN clinical course.
• Viral culture or immunofluorescence 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.

Imaging Studies:

• Magnetic resonance imaging (MRI) lesions attributable to HZ were seen in the brain stem and cervical cord in 56% (9/16) of patients.
• At 3 months after onset of HZ, 56% (5/9) of patients with an abnormal MRI had developed PHN.
• Of the 7 patients who had no HZ-related lesions on MRI, none had residual pain.

Treatment

Treatment for postherpetic neuralgia depends on the type and characteristics of pain experienced by the patient. Possible options include:

• Lidocaine skin patches. These are small, bandage-like patches that contain the topical, pain-relieving medication lidocaine. The patches, available by prescription, must be applied directly to painful skin to deliver relief for four to 12 hours. Patches containing lidocaine can also be used on the face, taking care to avoid mucus membranes e.g. eyes, nose and mouth.
• Analgesics. Pain control is essential to quality patient care; it ensures patient comfort. Most analgesics have sedating properties, which are beneficial for patients who experience pain.
  • Topical analgesics. Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.^[2]
• Opioids. Some people may need prescription-strength pain medications, such as tramadol (Ultram) or fentanyl (Duragesic), to control their pain. However, these drugs are narcotics and can be addictive.
• Antidepressants. These drugs affect key brain chemicals, including serotonin and norepinephrine, that play a role in both depression and how your body interprets pain. Doctors typically prescribe antidepressants for postherpetic neuralgia in smaller doses than they do for depression. Tricyclic antidepressants, including amitriptyline, seem to work best for deep, aching pain. They don't eliminate the pain, but they may make it easier to tolerate. Other prescription antidepressants (e.g. venlafaxine, bupropion and selective serotonin reuptake inhibitors) may be off-label used in postherpetic neuralgia and generally prove less effective, although they may be better tolerated than the tricyclics.
• Anticonvulsants. These agents are used to manage severe muscle spasms and provide sedation in neuralgia. They have central effects on pain modulation. Medications such as phenytoin (Dilantin, Phenytek), used to treat seizures, also can lessen the pain associated with postherpetic neuralgia. The medications stabilize abnormal electrical activity in the nervous system caused by injured nerves. Doctors often prescribe another anticonvulsant called carbamazepine (Carbatrol, Tegretol) for sharp, jabbing pain. Newer anticonvulsants, such as gabapentin (Neurontin) and lamotrigine (Lamictal), are generally tolerated better and can help control burning and pain.
• Corticosteroids. These agents have anti-inflammatory properties. However, glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli. Intrathecal administration of methylprednisolone may be beneficial.^[3]
• Antiviral agents. The goal of antivirals is to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency. Famciclovir (Famvir) -- Pro-drug that, when biotransformed into active metabolite penciclovir, may inhibit viral DNA synthesis/replication.
• Anecdotal testimonies from patients have suggested that smoking marijuana relieves the pain in much the same way as it relieves the pain of multiple sclerosis.

In some cases, treatment of postherpetic neuralgia brings complete pain relief. But most people still experience some pain, and a few don't receive any relief. Although some people must live with postherpetic neuralgia the rest of their lives, most people can expect the condition to gradually disappear on its own within five years.

Caution: Although often recommended, Transcutaneous electrical nerve stimulation (TENS) may be contraindicated for Postherpetic Neuralgia, as there is concern that, if turned up too high and/or left on the Trigeminal nerve too long, it may stimulate Postherpetic neuralgia rather than relieving it. One indicator of overuse of TENS with Postherpetic neuralgia patients involves significant earwax production as a result of overstimulation of the Trigeminal nerve, followed by tinnitus and intense Postherpetic neuralgia pain that increases over time. Note: If a decision is made to use TENS on the Trigeminal nerve of Postherpetic neuralgia patients, the unit should never be turned high enough to move the muscles (a recommendation in all types of TENS use, according to the UK department of Health.^[4])

Prognosis

• The natural history of PHN involves slow resolution of the pain syndrome.
• In those patients who develop PHN, most will respond to agents such as the tricyclic antidepressants.
• A subgroup of patients may develop severe, long-lasting pain that does not respond to medical therapy. Continued research for new agents is necessary.

Prevention

Primary prevention

In 1995, the Food and Drug Administration (FDA) approved the vaccine to prevent chickenpox. Its effect on PHN is still unknown. The vaccine — made from a weakened form of the varicella-zoster virus — may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.

Recently, Merck has tested a new vaccine (Zostavax) against shingles.^[5] This vaccine is a more potent version of the chickenpox vaccine. Evidence indicates that the vaccine reduced the incidence of shingles by 51 percent. Additionally, the vaccine reduced the incidence of PHN by two-thirds compared to placebo. However, the vaccine's protective effects diminished over the three years that most patients were followed.^[6] In December 2005, an FDA advisory committee unanimously agreed that the vaccine is safe and effective for persons over 60 years old.^[7] This was followed on 2006-05-26 by the FDA formally approving the use of the vaccine for that same age group.^[8] Further studies may demonstrate if there is benefit in patients 50-59 years old and if a booster dose is recommended.

Secondary prevention

• A meta-analysis reported that treating zoster at the time of rash with antiviral agents such as acyclovir can reduce the chance of postherpetic neuralgia.^[9]
• A randomized controlled trial found that amitryptyline 25 mg per night for 90 days starting with two days of onset of rash can reduce the inicidence of postherpetic neuralgia from 35% to 16% (number needed to treat is 6).^[10]

• U.S. Pharmacist. Postherpetic Neuralgia. A High-Risk Complication in Seniors with Herpes Zoster
• Information on Postherpetic Neuralgia