Herpes zoster reactivation, shingles, affects 0.2% of the population and postherpetic neuralgia (PHN) occurs in 10 -15% of patients following an episode of shingles, with the greatest risk in the elderly. A retrospective review involved 23 consecutive patients attending a tertiary complex pain clinic (University Hospital of Wales, Cardiff and Vale University Local Health Board), who were treated with topical gabapentin gel. Twenty patients (4 male) treated with topical gabapentin had severe chronic pain conditions: post-surgical pain, complex regional pain syndrome (CRPS), painful diabetic polyneuropathy, vulvovaginodynia (VVD), trigeminal neuralgia, autonomic cephalalgia, pudendal neuralgia and coccygodynia. Three patients had postherpetic neuralgia (PHN); all female aged 74, 83 and 85 years. The mean duration of PHN was 9 months (range 3-24 months), involving the ophthalmic division of the trigeminal nerve and intercostal nerve. All continued to suffer pain, described as pins and needles, prickly, sensitive to touch, with occasional stabbing or burning. Previous and ongoing treatments included: lidocaine patches; codeine; acetaminophen, capsaicin cream; oral pregabalin or gabapentin; lidocaine and depot steroid local infiltration; acupuncture and Botox injection. All three PHN patients reported intolerance to oral pregabalin and or gabapentin. The pre-treatment median pain severity (NRS, 0=no pain to 10=worst possible pain), was 7 for PHN and 8 for other chronic pain group. The median quality of life (0=low to 10=high) and chronic pain sleep inventory (0=maximal disruption to 10=no disruption) scores pre-treatment were 3.5 and 6 for PHN and 5 and 6 for other chronic pain groups, respectively. A topical formulation of 6% w/w gabapentin was applied three times per day to the affected site, maximal area 20cm2, and all patients were assessed monthly for pain, quality of life and sleep inventory scores over a period of 6 months. 20 of the 23 patients benefitted from topical gabapentin, a reduction in mean pain scores from 8.2 to 5.6 after 1 month (11 achieved a clinically meaningful 30% reduction in pain). Two of the three PNH patients benefited, with a percentage reduction in pain (60%, 57% and 0%), improvement in quality of life (42%, 300% and 0%) and sleep (33%, 0% and 0%) after 1 month. Interestingly all of the patients that responded to topical gabapentin treatment experienced pain relief within 1 hour of application.

   Multiple studies have already demonstrated the efficacy of oral gabapentin in treating chronic neuropathic pain, however efficacy is often limited by dose dependent toxicity. Although this patient population was small, these findings support the use of topical gabapentin in the treatment of PHN and potentially other painful neuropathy.

  Elderly patients exhibit a higher incidence of several neuropathic pain conditions than younger individuals. Systemic treatment of neuropathic pain in the elderly usually requires lower dosing, slower titration, and more monitoring (for efficacy, adverse effects) than in younger patients due to drug factors (altered pharmacokinetics and pharmacodynamics) and patient factors (comorbidities, polypharmacy, frailty). "Despite the availability of several options, treatment of neuropathic pain is not optimal, as medications provide only a partial effect and adverse effects can limit dose escalation, resulting in suboptimal dosing. An often quoted perspective is that less than 50% experience satisfactory pain relief, and side effects are common."

   Dr. Jana Sawynok of Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, notes that "topical analgesics are of interest because of their comparable efficacy to oral agents, good tolerability and safety, and potential to be add-on therapies to oral treatments. 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, indicate that topical preparations produce pain relief in neuropathic pain... Combinations of different drug classes are being explored, with the rationale that augmented analgesia may occur due to different mechanisms (synergy or additivity) but side effects may differ (drugs represent different classes) and be within tolerable limits. Additional lines of exploration involve comparisons of low-dose combinations with high-dose monotherapy, as this may improve tolerability."

    "Topical analgesics are drugs applied locally to the surface of the skin (usually as patches, gels, or creams) with local actions in the tissue on sensory nerve endings and adjacent cellular structures such as immune cells and keratinocytes. They differ from transdermal analgesics, where drugs are absorbed into the systemic circulation and act at remote sites within the central nervous system (e.g. fentanyl, buprenorphine). Topical analgesics are of interest due to their low systemic drug levels and minimal systemic side effects and drug interactions, and these properties make them attractive options for the elderly, either as monotherapies or as potential add-on therapies to oral analgesics."

Summary of perspectives on topical analgesics and relevance to the elderly

1) Topical analgesics are effective in a proportion of those with neuropathic pain, and can produce a degree of analgesia that is comparable with that of oral agents.
2) Topical analgesics are well tolerated, with adverse effects being mainly due to localized skin reactions. Low systemic levels occur following topical administration, and do not contribute to systemic adverse effects or drug interactions.
3) Topical analgesics may be used as alternative analgesics (when systemic analgesics are not tolerated) or as add-on analgesics when an oral agent produces a partial effect (their addition does not increase the side effect burden).
4) Only a limited number of topical analgesics are currently approved, but there is interest in investigational agents that recruit several potential mechanisms of action, and additional options may become available.
5) Topical analgesics have the potential to contribute to improved pain management in the elderly based on their efficacy, adverse effect profile, potential for use as add-on therapies, and potential for oral analgesic-sparing effects with ensuing reduction in adverse effects.

Drugs Aging. 2014 Dec;31(12):853-62.
Eur J Pain. 2014 Apr;18(4):465-81.