Review of current guidelines on the care of postherpetic neuralgia

An unfortunate minority of patients with acute herpes zoster (AHZ) experience pain beyond the typical 4-week duration, and roughly 10% develop the distressing complication of postherpetic neuralgia (PHN), often defined as pain persisting for > 4 months after the onset of the rash. Elderly patients are at increased risk of PHN. The pathophysiology of PHN is complex, likely involving both peripheral and central processes. This complexity may create opportunities for pharmacologic interventions with multiple differing mechanisms of action. Consequently, complementary combinations of pharmacologic agents are frequently more effective than any monotherapy. Current US and international guidelines on the care of patients with PHN are reviewed and interpreted here to facilitate their effective incorporation into the practice of primary care physicians, acknowledging the contrasts that often exist between the clinical trial populations analyzed to craft so-called evidence-based medicine and the individual patients seen in daily practice, many of whom may not have been candidates for those clinical trials. First-line treatments for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the topical lidocaine 5% patch. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are recommended as either second- or third-line therapies in different guidelines. Therapies that have demonstrated effectiveness for other types of neuropathic pain are discussed, such as serotonin-norepinephrine reuptake inhibitors, the anticonvulsants carbamazepine and valproic acid, and botulinum toxin. Invasive procedures such as sympathetic blockade, intrathecal steroids, and implantable spinal cord stimulators have been studied for relief of PHN, mainly in patients refractory to noninvasive pharmacologic interventions. The main guidelines considered here are those issued by the American Academy of Neurology for the treatment of postherpetic neuralgia (2004) and general guidelines for the treatment of neuropathic pain issued by the Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain (2007) and the European Federation of Neurological Societies (2010).     

Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study

This study compared the efficacy of topical lidocaine patches versus vehicle (placebo) patches applied directly to the painful skin of subjects with postherpetic neuralgia (PHN) utilizing an ‘enriched enrollment' study design. All subjects had been successfully treated with topical lidocaine patches on a regular basis for at least 1 month prior to study enrollment. Subjects were enrolled in a randomized, two-treatment period, vehicle-controlled, cross-over study. The primary efficacy variable was ‘time to exit'; subjects were allowed to exit either treatment period if their pain relief score decreased by 2 or more categories on a 6-item Pain Relief Scale for any 2 consecutive days. The median time to exit with the lidocaine patch phase was greater than 14 days, whereas the vehicle patch exit time was 3.8 days (P<0.001). At study completion, 25/32 (78.1%) of subjects preferred the lidocaine patch treatment phase as compared with 3/32 (9.4%) the placebo patch phase (P<0.001). No statistical difference was noted between the active and placebo treatments with regards to side effects. Thus, topical lidocaine patch provides significantly more pain relief for PHN than does a vehicle patch. Topical lidocaine patch is a novel therapy for PHN that is effective, does not cause systemic side effects, and is simple to use.     

Topical analgesics for neuropathic pain: Preclinical exploration,clinical validation,future development

Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an overview of the potential for topical analgesics to contribute to improved management of neuropathic pain. Mechanistic and preclinical studies indicate much potential for development of novel topical analgesics for neuropathic pain. In humans, two topical analgesics are approved for use in post‐herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8% patch), and there is evidence for efficacy in other neuropathic pain conditions. Comparative trials indicate similar efficacy between topical and oral analgesics. Not all individuals respond to topical analgesics, and there is interest in determining factors (patient factors, sensory characteristics) which might predict responsiveness to topical analgesics. There is a growing number of controlled trials and case reports of investigational agents (vasodilators, glutamate receptor antagonists, α2‐adrenoreceptor agonists, antidepressants, centrally acting drugs), including combinations of several agents, indicating these produce pain relief in neuropathic pain. There is interest in compounding topical analgesics for neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of neuropathic pain.     

Neurology (64)

Treatment of postherpetic neuralgia: an update. (University of Rochester School of Medicine and Dentistry, Rochester, NY) Drugs 2000;59:1113–1126.
This article provided an update on recent developments in the treatment of postherpetic neuralgia (PHN). In clinical trials, the topical lidocaine patch, gabapentin, and controlled release oxycodone have been shown to provide superior pain relief in patients with PHN when compared with placebo. It has also been demonstrated that the tricyclic antidepressant nortriptyline provides equivalent analgesic benefit when compared with amitriptyline, but is better tolerated. Based on these results, nortriptyline can now be considered the preferred antidepressant for treatment of PHN. The topical lidocaine patch, gabapentin, and controlled release oxycodone all appear to be as effective as tricycline antidepressants in the treatment of patients with PHN, and the results of these recent studies suggest that each of these treatments should be considered early in the course of treatment. Additional controlled trials are needed to compare the efficacy and tolerability of these 4 treatments for patients with PHN.     

Sequential medication strategies for postherpetic neuralgia: a cost-effectiveness analysis.

Several medications are recommended for relief of postherpetic neuralgia (PHN). A sequential treatment algorithm has been suggested, but its cost-effectiveness is unclear. We developed a decision model to estimate the cost-effectiveness of this algorithm compared with other sequential medication strategies in 70-year-olds with PHN, using literature data to model medication-related PHN relief while also accounting for severe medication side effects. Hypothetical patients with and without coronary artery disease (CAD) were considered separately, with and without localized pain. Sequential medication switches occurred as the result of inadequate relief or intolerable side effects. Probabilistic sensitivity analyses were performed to estimate the favorability of each medication early in treatment sequences. In patients without CAD, tricyclic and gabapentin were equally favored as initial therapy if mortality with tricyclic use was not increased, but gabapentin was strongly favored if it was. In patients with CAD, gabapentin was overwhelmingly favored. In either patient group, opioids, pregabalin, and tramadol were not favored as initial therapy but were sensible choices later in treatment sequences. The lidocaine patch was a reasonable first choice in patients with localized PHN. Our analysis supports the suggested treatment algorithm, with cost-effectiveness ratios within acceptable ranges for medications given sequentially, based on literature-based estimates of effectiveness and tolerability. PERSPECTIVE: This article examines the cost-effectiveness of recommended sequential treatment strategies for postherpetic neuralgia. This decision analysis-based synthesis of effectiveness and cost data found that recommended treatment algorithms are also economically reasonable.     

Sympathetic nerve blocks in mandibular herpes zoster and postherpetic neuralgia

Sympathetic blocks have been indicated for the diagnosis and treatment of painful neuropathic conditions, such as herpes zoster (HZ) and postherpetic neuralgia (PHN). The purpose of this article is to report a case of mandibular HZ and PHN in an HIV-positive patient, and discuss the efficacy of sympathetic nerve blocks for pain relief and prevention of PHN.     

Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study

OBJECTIVE: Our goal was to perform a pilot study to assess the effectiveness and tolerability of a topical lidocaine patch (Lidoderm) for the treatment of peripheral neuropathic pain conditions other than postherpetic neuralgia. DESIGN: This was an open-label prospective study. PATIENTS: Sixteen patients with refractory peripheral neuropathic pain conditions who had reported intolerable side effects or inadequate pain relief with antidepressant, anticonvulsant, antiarrhythmic, and opioid medications participated in this study. Diagnoses included postthoracotomy pain, stump neuroma pain, intercostal neuralgia, diabetic polyneuropathy, meralgia paresthetica, complex regional pain syndrome, radiculopathy, and postmastectomy pain. OUTCOME MEASURES: A six-item Pain Relief Scale was used (0 = worse pain, 1 = no change, 2 = slight relief, 3 = moderate relief, 4 = a lot of relief, 5 = complete relief). RESULTS: Moderate or better pain relief was reported by 13 of the 16 participants (81%). One patient stopped treatment after 4 days due to lack of relief. The remaining 15 patients had a mean duration of patch use of 6.2 weeks with continued relief. Only 1 patient reported a side effect, a mild skin irritation. CONCLUSIONS: The Lidoderm patch provided clinically meaningful pain relief in most of these refractory neuropathic pain patients without side effects. Controlled trials need to be performed to confirm these preliminary findings.     

Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. (Department of Pain Medicine and Palliative Care, Beth Lsrael Medical Center, New York, NY) Clin J Pain 2000;16:205–208.

Our goal was to perform a pilot, open‐label, prospective study to access the effectiveness and tolerability of a topical lidocaine patch (Lidoderm) for the treatment of peripheral neuropathic pain conditions other than postherpetic neuralgia. Sixteen patients with refractory peripheral neruopathic pain conditions who had reported intolerable side effects or inadequate pain relief with antidepressant, anticonvulsant, antiarrhythmic, and opioid medications participated in this study. Diagnoses included postthoracotomy pain, stump neuroma pain, intercostal neuralgia, diabetic polyneuropathy, meralgia paresthetica, complex regional pain syndrome, radiculopathy, and postmastectomy pain. A 6‐item Pain Relief Scale was used. Moderate or better pain relief was reported by 13 of the 16 participants (81%). One patient stopped treatment after 4 days due to lack of relief. The remaining 15 patients had a mean duration of patch use of 6.2 weeks with continued relief. Only 1 patient reported a side effect, a mild skin irritation. Conclude the Lidoderm patch provides clinically meaningful pain relief in most of these refractory neuropathic pain patients without side effects. Controlled trials need to be performed to confirm these preliminary findings. Comment by Tat‐Leang Lee, M.D. This is an interesting study that highlighted a simple, efficacious method for the treatment of resistant neuropathic pain. As this was a pilot study using an open‐label method, and treating a heterogenous group of neuropathic pain conditions, caution should be adopted in the interpretation of the results. What remains unanswered is the reason for the success of the lidocaine patch, particularly when previous studies have documented the failure of EMLA in the treatment of neuropathic pain. Indeed, several patients who participated in this study had used EMLA unsuccessfully before, although no details on its administration was reported. Both the lidocaine patch and EMLA contain 5% lidocaine, which presumably would result in greater penetration by the EMLA cream. Therefore, a placebo‐controlled randomized trial is needed to confirm the findings of this pilot study. Nevertheless, this is a promising treatment that is convenient, lacks systemic effect, easily added‐on to existing treatment, and with only minor side effects, that is worth considering for our patients.     

Efficacy of Qutenza® (capsaicin) 8% patch for neuropathic pain: A meta-analysis of the Qutenza Clinical Trials Database

Qutenza® is a capsaicin patch used to treat peripheral neuropathic pain, including postherpetic neuralgia (PHN) and human immunodeficiency virus-associated neuropathy (HIV-AN). The Qutenza Clinical Trials Database has been assembled to more fully characterize the effects of Qutenza. We conducted a within-subject meta-analysis of Qutenza studies to further define the medication’s efficacy profile across studies. The meta-analysis combined individual patient data from randomized, controlled studies of Qutenza in peripheral neuropathic pain (1458 subjects treated with approved doses of Qutenza or control patches; 1120 with PHN and 338 with HIV-AN). These 7 studies had similar designs and were performed with the high-dose 8% capsaicin Qutenza patch and a 0.04% low-dose control patch. The difference between treatment groups for the primary efficacy end point of percentage change from baseline to weeks 2 to 12 on pain intensity score was calculated. Response was defined as a ?30% decrease in mean pain intensity score during weeks 2 to 12. The overall between-group difference in percentage change from baseline in pain intensity was 8.0% (95% confidence interval 4.6, 11.5; P < .001), which statistically significantly favored Qutenza over low-dose control. Qutenza superiority was demonstrated for both PHN and HIV-AN patients for the primary end point and the end point proportion of 30% pain reduction response, and for PHN patients for the end point of proportion of 50% pain reduction response. These results confirm that Qutenza is effective for the treatment of both PHN and HIV-AN compared to low-dose control patch.     

Post-herpetic Neuralgia: a Review

Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients.     

Pregabalin for neuropathic pain based on recent clinical trials

Pregabalin is a ligand for the α-2-δsubunit of voltagegated calcium channels with anticonvulsant, analgesic, and anxiolytic properties. It has predictable absorption across the gastrointestinal tract, is neither metabolized nor protein-bound, and has minimal drug-drug interactions. It is effective with two or three-times daily dosing in a dose range of 150 to 600 mg daily. Seven published prospective, randomized clinical trials in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) demonstrate pain relief, decreased sleep interference, and improvements in several secondary outcome measures. The 50% responder rates for PHN and DPN compare favorably with other first-line agents for neuropathic pain. Pregabalin is well tolerated in most patients with infrequent severe adverse effects. Pregabalin is an important addition to the treatment armamentarium for neuropathic pain.     

Postzosterneuralgie

Postherpetic neuralgia is considered to be a neuropathic pain syndrome. Typically, patients experience pain in the dermatomes of skin lesions persisting for more than 3 months after skin restitution. About 10?% of patients with herpes zoster develop postherpetic neuralgia. Its prevalence increases with age. Common clinical symptoms include continuous burning pain, sharp pain attacks, and allodynia. Additionally, sensory hyperactivation or loss in the affected skin area is present. Pathophysiology includes mechanisms of peripheral and central sensitization, based on damaged nerve fibers as the main mechanisms for pain generation and its maintenance. Clinical studies did show pain relief in postherpetic neuralgia after administration of antidepressants, antiepileptic drugs, opioids, and topical capsaicin and lidocaine. Nevertheless, about one third of patients do not respond to conventional treatment. Given the fact that postherpetic neuralgia is considered to be a chronic pain disease, a multidisciplinary treatment approach is necessary.     

Topical Analgesics in the Management of Acute and Chronic Pain

Oral analgesics are commonly prescribed for the treatment of acute and chronic pain, but these agents often produce adverse systemic effects, which sometimes are severe. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. This article describes the results of a systematic review of the efficacy of topical analgesics in the management of acute and chronic pain conditions. A literature search of MEDLINE/PubMed was conducted using the keywords topical analgesic AND chronic pain OR acute pain OR neuropathic pain and focused only on individual clinical trials published in English-language journals. The search identified 92 articles, of which 65 were eligible for inclusion in the review. The most commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs (n=27), followed by lidocaine (n=9), capsaicin (n=6), amitriptyline (n=5), glyceryl trinitrate (n=3), opioids (n=2), menthol (n=2), pimecrolimus (n=2), and phenytoin (n=2). The most common indications were acute soft tissue injuries (n=18), followed by neuropathic pain (n=17), experimental pain (n=6), osteoarthritis and other chronic joint-related conditions (n=5), skin or leg ulcers (n=5), and chronic knee pain (n=2). Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy. Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain.     

Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study

Peripheral neuropathic pain syndromes (PNPS) are difficult to treat because commonly used analgesics are often ineffective when, for example, touch-evoked allodynia, hyperalgesia, and pain paroxysms are present. To investigate whether lidocaine patch 5% treatment is also effective in postherpetic neuropathy (PHN) and in other PNPS, 40 patients with various forms and localizations of PNPS completed a prospective, randomized, placebo-controlled, two-way, cross-over study in three medical hospitals. Patients suffering from pain in a localized skin area with intensity above 40 mm visual analog scale (VAS) and a stable consumption of pain medication were included in this study. The study was divided into four phases: 3-day run-in phase, treatment phase 1, wash-out period, and treatment phase 2, each lasting 1 week. At the discretion of the patients, up to four patches (covering a maximum of 560 cm2) were applied onto the maximally painful area for 12 consecutive hours daily, always either by day or at night. Throughout the four phases, ongoing pain, allodynia, quality of neuropathic symptoms, quality of sleep, and adverse events were assessed. When, after the wash-out period, the pain intensity scores did not return to the pre-treatment values (+/-20%), these patients were excluded from the study. The present study revealed that, as an add-on therapy, the lidocaine patch 5% was clearly effective in reducing ongoing pain (P=0.017) and allodynia (P=0.023) during the first 8 h after application and that the patches also worked well over a period of 7 days (P=0.018) in diverse focal PNPS. Calculation of the numbers needed to treat (NNT) to obtain one patient with more than 50% relief of ongoing pain revealed that the NNT of 4.4 in the present study compared reasonably well with other studies of PHN, such as topically applied capsaicin (NNT: 5.3-infinity) or systemic treatment with gabapentin (NNT: 3.2-5.0).     

Symptom profiles differ in patients with neuropathic versus non-neuropathic pain.

The distinction between neuropathic and non-neuropathic pain reflects partially distinct mechanisms and patterns of treatment response. It was therefore hypothesized that patients with neuropathic and non-neuropathic pain have different profiles of symptoms and signs. To test this hypothesis, pain intensity, unpleasantness, quality, and spatial characteristics were examined in 618 patients with 1 of 3 peripheral neuropathic pain conditions (painful diabetic peripheral neuropathy, painful idiopathic sensory polyneuropathy, or postherpetic neuralgia), osteoarthritis pain, or low back pain. These assessments were conducted before treatment had begun in clinical trials of lidocaine patch 5% administered alone or with stable dosages of other analgesics. Patients with osteoarthritis pain and low back pain did not differ in their profile of pain quality and spatial characteristics and were combined to form a group of patients with non-neuropathic pain. In univariate analyses, patients with peripheral neuropathic pain reported significantly more intense hot, cold, sensitive, itchy, and surface pain and significantly less intense dull and deep pain than patients with non-neuropathic pain. In a multivariate analysis, the overall pattern of pain quality and spatial characteristics differed significantly between patients with neuropathic and non-neuropathic pain. In addition, specific pain quality and spatial characteristics improved the discrimination of patients with neuropathic and non-neuropathic pain in a logistic regression model that adjusted for demographic covariates and overall pain intensity and unpleasantness. PERSPECTIVE: The results indicate that the distinction between neuropathic and non-neuropathic pain is reflected in different profiles of pain quality and spatial characteristics and suggest that the assessment of patterns of pain symptoms might contribute to the identification of distinct pathophysiologic mechanisms and the development of mechanism-based treatment approaches.     

The use of gabapentin for the treatment of postherpetic neuralgia

BACKGROUND: Varicella-zoster virus causes chickenpox and can reemerge later in life to cause herpes zoster or shingles. One of the most common and disabling complications of herpes zoster is postherpetic neuralgia (PHN). OBJECTIVES: This article reviews the current primary literature about the efficacy and tolerability of gabapentin for the treatment of PHN. Gabapentin pharmacokinetics and drug interactions are also reviewed. METHODS: A literature search in the English language was conducted using OVID Web, which contained the following databases: MEDLINE (1966-present), EMBASE (1980-2002), Current Contents/Clinical Medicine (1999-2002), Cochrane Controlled Trials Register (1898-present), Cochrane Database of Systemic Reviews (fourth quarter, 2002), and International Pharmaceutical Abstracts (1970-2002). Search terms used were postherpetic neuralgia; zoster; gabapentin; neuropathic pain; pain; pharmacoeconomic; cost; controlled clinical trial; randomized, controlled trial; postherpetic neuralgia and gabapentin; gabapentin and pain; treatment and postherpetic neuralgia; gabapentin and age; gabapentin and gender; gabapentin and ethnicity; and gabapentin and pharmacokinetics. RESULTS: Gabapentin displays nonlinear absorption kinetics, is minimally protein bound (< 3%), has a high mean (SD) volume of distribution (50.4 [8.0] L), and is excreted via the kidneys as unchanged drug. Two randomized, placebo-controlled, parallel-group, multicenter clinical trials demonstrated the effectiveness of gabapentin at doses of up to 3600 mg/d to significantly reduce pain (P < 0.01 and P < 0.001), improve sleep (P < 0.01), and improve some parameters on the Short Form-McGill Pain Questionnaire (P < 0.05). Dizziness and somnolence were the most common side effects leading to withdrawal from the trials. The recommended dosage in adults is 300 mg at bedtime on day 1,300 mg BID on day 2, and 300 mg TID on day 3, titrating up as needed to 2400 to 3600 mg/d. To reduce adverse events in patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance. CONCLUSIONS: Gabapentin appears to be effective and well tolerated for the short-term treatment of PHN. However, future controlled studies are needed to determine whether the effectiveness of gabapentin for PHN is maintained for > 2 months, to establish the optimal dose of gabapentin for PHN, and to compare the efficacy of gabapentin with that of other pharmacologic agents used for the treatment of PHN.     

Cognitive Function in Older Patients with Postherpetic Neuralgia

Background and aims

Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN).

Methods

This cross‐sectional study ( clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. Participants: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision‐making, and visual memory (Cantab^®, Cambridge).

Results

Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision‐making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers.

Conclusion

This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.     

Herpes zoster in older adults. (Duke University Medical Center, Durham, NC) Clinical Infectious Diseases. 2001;32:1481–1486.

Herpes zoster (HZ) strikes millions of older adults annually worldwide and disables a substantial number of them via postherpetic neuralgia (PHN). Key aged‐related clinical, epidemiological, and treatment features of zoster and PHN are reviewed in this article. HZ is caused by renewed replication and spread of the varicella‐zoster virus (VZV) in sensory ganglia and afferent peripheral nerves in the setting of age‐related, disease‐related, and drug‐related decline in cellular immunity to VZV. VZV‐induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities in daily living, and reduced quality of life in elderly patients. Recently, attempts to reduce or eliminate HZ pain have been bolstered by the findings of clinical trials that antiviral agents and corticosteroids are effective treatment for HZ and that tricyclic antidepressants, topical lidocaine, gabapentin, and opiates are effective treatment for PHN. Although these advances have helped, PHN remains a difficult condition to prevent and treat in many elderly patients. Comment by Miles Day, M.D. This article reviews the epidemiology clinical features diagnosis and treatment of acute herpes zoster. It also describes the treatment of postherpetic neuralgia. While this is a good review for the primary care physician, the discussion for the treatment for both acute herpes zoster and postherpetic neuralgia do not mention invasive therapy. It is well documented in pain literature that sympathetic blocks with local anesthetic and steroid as well as subcutaneous infiltration of active zoster lesions not only facilitate the healing of acute herpes zoster but also prevents or helps decrease the incidence of postherpetic neuralgia. All patients who present to the primary care physician with acute herpes zoster should have an immediate referral to a pain management physician for invasive therapy. The treatment of postherpetic neuralgia is a challenging experience both for the patient and the physician. While the treatments that have been discussed in this article are important, other treatments are also available. Regional nerve blocks including intercostal nerve blocks, root sleeve injections, and sympathetic blocks have been used in the past to treat postherpetic neuralgia. If these blocks are helpful, one can proceed with doing crynourlysis of the affected nerves or also radio‐frequency lesioning. Spinal cord stimulation has also been used for those patients who are refractory to noninvasive and invasive therapy. While intrathecal methylprednisolone was shown to be effective in the study quoted in this article one must be cautious not to do multiple intrathecal steroid injections in these patients. Multilple intrathecal steroid injections can lead to archnoiditis secondary to the accumulation of the steroid on the nerve roots and in turn causing worsening pain.     

Advances in the management of neuropathic pain

Much progress has been made in the assessment and management of neuropathic pain over the past 5 years. Assessment has improved with the Neuropathic Pain Scale, a new, easily administered, diagnostic tool. Mechanistically, recent studies indicate that peripheral neuropathic pain is generated through a focal inflammatory process rather than axonal destruction. This process also appears to involve mRNA regulation of fast sodium channels, which produce ectopic discharges and are presumably responsible for pain generation. In addition the entire neuraxis undergoes neuroplastic changes as a result of peripheral nerve injury. The available clinical trial data indicate that newer antiepileptic drugs (AEDs), most notably gabapentin, are better alternatives to older medications such as carbamazepine or phenytoin in the treatment of neuropathic pain. Gabapentin is at least as good with respect to actual pain relief as the antidepressants, including amitriptyline, but has a much better safety profile with minimal drug-drug interactions and side effects. Mexiletine is a reasonable alternative agent in patients who have not had a satisfactory response to, or cannot tolerate, the AEDs or antidepressants. Long-acting opioids should be considered in patients refractory to these adjunctive agents. With the advent of the topical lidocaine patch, the first drug with an FDA-approved indication for postherpetic neuralgia, a revolutionary new agent is now available for the treatment of neuropathic pain that does not have any systemic side effects.