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Postherpetic neuralgia (PHN), defined as pain in the affected dermatome that persists or appears after the rash of herpes zoster (HZ) has healed (i.e., after all crusts have fallen off and reepithelialization is complete), is the most frequent complication of herpes zoster. Because healing is almost always complete within 4 weeks of rash onset, PHN is often defined as pain that persists or occurs 30 days or more after rash onset. The overall incidence of PHN so defined has been reported to be 9% to 15% in retrospective postherpetic neuralgia.
Most patients with PHN describe three types of pain: (1) spontaneous, constant deep burning, throbbing, aching pain; (2) intermittent sharp, stabbing, shooting, lancinating pain, which may also be spontaneous; and (3) dysesthetic pain provoked by light tactile stimulation (allodynia), which usually lasts well beyond the duration of the stimulus (hyperpathia). Allodynia may also be provoked by cold. Allodynia is present in 90% or more of patients with PHN.
When patients with PHN are carefully studied, the involved skin almost always shows pigmentary changes and scarring, and there are major sensory abnormalities in the affected dermatome.
Age is the most significant risk factor for PHN, which is rare below the age of 40 years but occurs in more than 50% of persons with HZ who are 60 years old or older.
PHN is the most frequent complication of HZ in the immunocompetent host. The reported incidence and duration of PHN vary markedly, primarily because of variations in the definition of PHN employed, the patient populations studied, and the methods of surveillance. The overall incidence of PHN has been reported to be 9% to 14% in population-based studies.
Hope-Simpson, in explaining why the incidence of PHN that he recorded (14.3%) was substantially lower than that reported by others, pointed out that he included only patients whose neuralgia.
HZ and PHN are two clinically important diseases because of the large number of patients affected by HZ and the intractability of PHN. The treatments described for HZ and PHN are large in number and limited in success, and many of them are controversial. There is a general lack of well-controlled, well-designed studies to evaluate the treatment outcome for HZ and PHN. The many differences seen in these outcomes often relate to the differences in defining PHN.
Antiviral Therapy of Herpes Zoster: Effects on Acute Pain and Postherpetic Neuralgia
Despite limited understanding of its neurophysiology, there can be little doubt that PHN is a consequence of damage to neural tissues that innervate the affected dermatome. Because this damage is the direct result of the replication and spread of VZV during the preeruptive and acute phase of HZ.
In two small double-blind, placebo-controlled clinical trials, 5 days of treatment with intravenous acyclovir reduced virus shedding, accelerated rash healing, and reduced acute pain in patients with HZ, but there was no effect on the development of PHN. VZV is approximately 10-fold less sensitive to acyclovir than herpes simplex virus, and thus inhibition of VZV replication.
Two prodrugs, famciclovir and valacyclovir, which have substantially greater oral bioavailability than acyclovir, have been tested for efficacy in patients with HZ. Famciclovir is a prodrug of penciclovir, a nucleoside analogue similar to acyclovir in mechanism of action and antiviral activity against VZV.
Despite effects on acute pain, there is no clear evidence that treatment of HZ with acyclovir or related compounds that selectively inhibit VZV replication can prevent the development of PHN. The results of a number of clinical trials have been inconsistent, and meta-analyses of pooled data.
Tyring and associates examined the effect of famciclovir in a placebo-controlled trial involving 419 patients with HZ who were 18 years of age or older. Although the proportion of patients with PHN (defined as pain persisting or occurring after rash healing) was the same (44%) in famciclovir.
In a large study in which patients 50 years of age or older with HZ were treated with valacyclovir.
PHN is the most feared sequela of HZ. PHN is defined as persistent pain after the lesions of HZ heal. By this definition, the majority of patients have PHN because a large number have persistent pain in the immediate period following HZ. The majority of these patients, however, have pain completely resolve within 6 months. Therefore, do the patients that go on to become pain-free truly have PHN? This confusion has led to many claimers and disclaimers of various treatments of HZ preventing PHN (see previous discussion).
There are many treatments described for the treatment of PHN, many of them anecdotal. Unfortunately, the pain of PHN is often resistant to multiple treatment modalities. These resistant cases lead the patient and physician on a path of futile attempts to treat the agonizing pain. This section discusses the most common treatments of PHN, which include (1) topical agents, (2) systemic pharmacologic treatments, (3) neurostimulatory techniques, and (4) neuroablative techniques.
Topical AgentsAlthough the topical treatments for HZ provide symptomatic relief of the pain as well as germicidal treatment, the topical treatments for PHN are directed at the pain only. There are many topical treatments described for PHN. Topical anti-inflammatory agents have been used in the treatment.
Capsaicin cream has been reported successful in relieving the pain of PHN. This agent was introduced in 1987 for the treatment of PHN, and since then there have been conflicting reports on its efficacy. Capsaicin depletes unmyelinated sensory afferents of substance P, thus leading to a efficacy of this treatment has yet to be determined.
Topical lidocaine has been reported successful in the treatment of the pain of PHN.
Systemic Pharmacologic AgentsThe tricyclic antidepressants (TCAs) have been proven useful in a variety of neuropathic pain states.
Many patients with PHN complain of intermittent shooting pain that lasts from seconds to minutes. The nerve damage that occurs with HZ can lead to ectopic impulses from demyelinated segments, neuronal sprouts, and near the dorsal root ganglion. This pain can be responsive to sodium channel blocking drugs, such as the anticonvulsants (AC) and local anesthetics.
Swerdlow and Cundill determined that lancinating pain could be treated with a number of anticonvulsant drugs, including phenytoin, carbamazepine, clonazepam, and valproic acid. Because it has the greatest inhibition of voltage-sensitive sodium channels, carbamazepine has been the AC of choice. Carbamazepine, however, similar to most other AC, may have intolerable side effects. The new anticonvulsant, gabapentin (Neurontin) may replace the older ACs because of the extremely low side-effect profile.
Studies have shown systemic lidocaine to be effective in the treatment of several neuropathic pain disorders including PHN. The mechanism of systemic lidocaine is similar to that of the ACs.
The use of phenothiazines alone in neuropathic pain is controversial, although they are used frequently in combination with opioids and TCAs. There is evidence in animal studies that dopaminergic systems.
Neurostimulatory Techniques
Transcutaneous electrical nerve stimulation (TENS) is a conservative technique that has been reported effective in PHN as well as other neuropathic pain syndromes. Bohm stated that peripheral nerve injury pain that is sympathetically mediated responds the best to TENS.
Neuroablative TechniquesThe use of neuroablative procedures should always be tempered by the appreciation that a nerve lesion causes a disorganization of the central nervous system. Because PHN results from abnormal central nervous system processing of afferent information.