Postherpetic neuralgia 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 in that same dermatomic area. The neuralgia typically begins when
the herpes zoster vesicles have crusted over and begun to heal, but it can begin in the
absence of herpes zoster, in which case zoster sine herpete is presumed.
Treatment options for postherpetic neuralgia include antidepressants, anticonvulsants,
gabapentin enacarbil 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 and TENS.
Pathophysiology Postherpetic neuralgia is thought to be nerve
damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area
of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating
pain, and may persist or recur for months, years, or for life.
A key factor in the neural plasticity underlying neuropathic pain is altered gene expression
in sensory dorsal root ganglia neurons. Injury to sensory nerves induces neurochemical, physiological
and anatomical modifications to afferent and central neurons, such as afferent terminal
sprouting and inhibitory interneuron loss. Following nerve damage, NaCl channel accumulation
causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 channel and upregulation
of TTX-sensitive Nav1.3 and TRPV1 channels. These changes contribute to increased NMDA
glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted
to the ipsilateral side. A combination of these factors could contribute to the neuropathic
pain state of postherpetic neuralgia. Frequency
In the United States each year approximately 1,000,000 individuals develop herpes zoster.
Of those individuals approximately 10-18% develop postherpetic neuralgia.
Less than 10 percent of people younger than 60 develop postherpetic neuralgia after a
bout of herpes zoster, while about 40 percent of people older than 60 do.
Predisposing factors Race: It may influence susceptibility to herpes
zoster. African Americans are one fourth as likely as Caucasians to develop this condition.
Often an older, debilitated or immune compromised population.
Signs and symptoms Symptoms:
With resolution of the herpes zoster eruption, pain that continues for three months or more
is defined as postherpetic neuralgia. Pain is variable, from discomfort to very
severe, and may be described as burning, stabbing, or gnawing.
Signs: Area of previous herpes zoster may show evidence
of cutaneous scarring. Sensation may be altered over the areas involved,
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. Lab and imaging studies
Lab Studies: No laboratory work is usually necessary.
Results of cerebrospinal fluid 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 clinical course of postherpetic neuralgia.
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. However, a rising titer secondary to viral
exposure rather than reactivation cannot be ruled out.
Imaging studies: Magnetic resonance imaging lesions attributable
to herpes zoster were seen in the brain stem and cervical cord in 56% of patients.
At three months after onset of herpes zoster, 56% of patients with an abnormal magnetic
resonance image had developed postherpetic neuralgia.
Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none
had residual pain. Treatment
Treatment for postherpetic neuralgia depends on the type and characteristics of pain experienced
by the patient. Pain control is essential to quality patient care; it ensures patient
comfort. Possible options include: Antiviral agents, such as famciclovir, are
given at the onset of attacks of herpes zoster to shorten the clinical course and to help
prevent complications such as postherpetic neuralgia. However, they have no role to play
following the acute attack once postherpetic neuralgia has become established.
Analgesics Locally applied topical agents
Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.
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 and 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., the eyes, nose
and mouth.
Systemically delivered Non-opiates such as paracetamol or the non-steroidal
anti-inflammatory drugs. Opioids provide more potent pain control and
the weaker members such as codeine may be available over the counter in combination
with paracetamol. Other opioids are prescription-only and include higher dosages of codeine, tramadol,
morphine or fentanyl. Most opioids have sedating properties, which are beneficial for patients
who experience pain.
Pain modification therapy Antidepressants. These drugs affect key brain
chemicals, including serotonin and norepinephrine, that play a role in both depression and how
the body interprets pain. Doctors typically prescribe antidepressants for postherpetic
neuralgia in smaller doses than they do for depression. Low dosages of tricyclic antidepressants,
including amitriptyline, seem to work best for deep, aching pain. They do not eliminate
the pain, but they may make it easier to tolerate. Other prescription antidepressants 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, 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 for sharp, jabbing pain. Newer anticonvulsants, such as gabapentin
and lamotrigine, are generally tolerated better and can help control burning and pain.
gabapentin enacarbil, an alpha-2-delta-1 ligand and a prodrug of gabapentin, was approved
by the FDA in 2012 for the management of postherpetic neuralgia.
Corticosteroids are commonly prescribed but a Cochrane Review found limited evidence and
no benefit. Other non-pharmacological treatments for postherpetic
neuralgia include the following: Acupuncture.
Moxibustion. Relaxation techniques. These can include breathing
exercises, visualization and distraction. Heat therapy.
Cold therapy. Cold packs can be used. Transcutaneous Electrical Nerve Stimulation.
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.
In some cases, treatment of postherpetic neuralgia brings complete pain relief. But most people
still experience some pain, and a few do not 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.
Prognosis The natural history of postherpetic neuralgia
involves slow resolution of the pain syndrome. In those patients who develop postherpetic
neuralgia, most 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
approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia
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.
In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck
against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence
shows that it reduces the incidence of postherpetic neuralgia. The CDC recommends use of this
vaccine in all persons over 60 years old. Secondary prevention
An April 2013 Cochrane Collaboration meta-analysis of 6 Randomized Control Trials investigating
PO antiviral medications given within 72 hours after the onset of Herpes Zoster rash in immunocompetent
people for preventing postherpetic neuralgia found no significant difference between placebo
and aciclovir. Combining four RCTs, 44.1% of the aciclovir treatment group developed
herpetic neuralgia whereas 53.3% of the placebo group developed herpetic neuralgia. Heterogeneity
between the four RCTs was moderate: Chi2 =3.36, df = 2; I2 = 40%. Nor was a significant difference
in preventing the incidence of PHN found in the one RCT included in the meta-analysis
that compared placebo to PO famciclovir treatment within 72 hours of HZ rash onset. Studies
using valaciclovir treatment were not included in the meta-analysis. PHN was defined as pain
at the site of the dermatomic rash at 120 days after the onset of rash, and incidence
was evaluated at 1, 4, and 6 months after rash onset. There was a slight reduction in
the incidence of pain at 4 weeks after the onset of rash in the aciclovir group versus
the placebo group. If patients are prescribed PO antiviral agents after the onset of rash,
they should be informed that their chances of developing PHN are no different than those
not taking PO antiviral agents. A randomized controlled trial found that amitriptyline
25 mg per night for 90 days starting within two days of onset of rash can reduce the incidence
of postherpetic neuralgia from 35% to 16%. Research directions
Gallium maltolate in a cream or ointment base has been studied in a case report as a treatment
of refractory postherpetic trigeminal neuralgia. References
External links Management of Herpes Zoster and Postherpetic
Neuralgia Clinical Trials for Shingles Pain
Herpes Zoster and Postherpetic Neuralgia: Prevention and Management
The Center for Shingles and Postherpetic Neuralgia Postherpetic Neuralgia. Mayo Clinic
Hempenstall K, Nurmikko TJ, Johnson RW, A'Hern RP, Rice AS. "Analgesic therapy in postherpetic
neuralgia: a quantitative systematic review". PLoS Med. 2: e164. doi:10.1371/journal.pmed.0020164.
PMC 1181872. PMID 16013891.