European Journal of Pain Supplements RSS feed: Current Issue. http://www.europeanjournalpainsupplements.com/?rss=yesElsevier Inc.en © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Inc. All rights reserved. European Journal of Pain Supplements1754-320742August 2010 © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.europeanjournalpainsupplements.com/article/PIIS1754320710705253/abstract?rss=yesSupplement introduction: Targeting the skin for treating peripheral neuropathic painTuro Nurmikko10.1016/S1754-3207(10)70525-3European Journal of Pain Supplements 4, 2 (2010)2010-08-01European Journal of Pain Supplements2010-08-0142S1754-3207(10)X0003-7155156http://www.europeanjournalpainsupplements.com/article/PIIS1754320710705265/abstract?rss=yesSUMMARY: In addition to homeostatic and immunologic barrier functions, the skin acts as a complex sensory organ. Traditionally, the sensory modality of pain was thought to be transduced exclusively by primary afferent neurons, but the concept of a neuro-immuno-cutaneous system (NICS) is becoming more recognized. This system involves signals between both neuronal and non-neuronal skin cells. The Transient Receptor Potential Vanilloid 1 (TRPV1) receptor plays an important role in the NICS. It is highly expressed on nociceptive sensory nerves, as well as on non-neuronal skin cells, especially keratinocytes. Keratinocytes, which account for 85% of the cells of the dermis, have a close anatomic relationship with peripheral nerves and have TRPV1 receptors on their surface. TRPV1 receptors have also been reported on Langerhans cells, sebocytes and sweat gland epithelium, although due to different staining techniques there is controversy about the actual amount. TRPV1 receptors are activated by capsaicin and the topical application of a high-concentration capsaicin patch has been shown to significantly reduce pain in patients with post-herpetic neuralgia or HIV-associated neuropathy. Given the emerging picture of the role played by cutaneous cells in pain transmission, this review will discuss the critical interplay between cutaneous cells and nociceptors, and how their interactions contribute to the pathophysiology of peripheral neuropathic pain. The role of the skin in peripheral neuropathic painGordon Irving10.1016/S1754-3207(10)70526-5European Journal of Pain Supplements 4, 2 (2010)2010-08-01European Journal of Pain Supplements2010-08-0142S1754-3207(10)X0003-7157160http://www.europeanjournalpainsupplements.com/article/PIIS1754320710705277/abstract?rss=yesSUMMARY: Neuropathic pain refers to pain that originates from a lesion or dysfunction of the peripheral or central nervous system. Common examples are painful diabetic neuropathy and post-herpetic neuralgia. Despite recent advances in the identification of pain-generating mechanisms and the introduction of evidence-based treatment guidelines, patients with neuropathic pain are challenging to manage. The currently available systemic therapies provide about half of affected patients with meaningful pain relief and are further limited by unwanted adverse effects, such as drowsiness and dizziness, and the need for multiple daily dosing. The traditional topical agents available for the treatment of neuropathic pain – lidocaine patch (5% w/w) and low-concentration capsaicin cream (0.075% w/w) – are generally free of systemic adverse effects but they have only modest efficacy, require cumbersome daily administration, and in the case of capsaicin cream can lead to discomfort and contamination of sensitive body areas, all of which may result in poor compliance. As patients are left with a difficult compromise between pain relief on the one hand and adverse effects and daily treatment regimens on the other, a clear unmet need remains in the management of neuropathic pain. A high-concentration capsaicin (8% w/w) patch that provides rapid and prolonged pain relief from a single application is a promising alternative treatment option for patients with peripheral neuropathic pain. Further elucidation of the specific pathophysiologic mechanisms which contribute to neuropathic pain and their translation into signs and symptoms should ultimately enable the design of optimal treatments for individual patients with neuropathic pain. Challenges with current treatment of neuropathic painThomas R. Tölle10.1016/S1754-3207(10)70527-7European Journal of Pain Supplements 4, 2 (2010)2010-08-01European Journal of Pain Supplements2010-08-0142S1754-3207(10)X0003-7161165http://www.europeanjournalpainsupplements.com/article/PIIS1754320710705289/abstract?rss=yesSUMMARY: HIV-associated neuropathy (HIV-AN) occurs frequently in patients with HIV infection or AIDS, but it is one of the more difficult forms of peripheral neuropathic pain to treat effectively. Results of two randomized, double-blind trials indicated that a 30-minute application of a high-concentration capsaicin (8% w/w) patch (NGX-4010; QUTENZA™) is the optimal dosage to alleviate pain associated with HIV-AN. A subsequent integrated efficacy analysis of the two trials revealed that a 30-minute application of the high-concentration capsaicin patch produced significantly greater pain relief than a low-concentration capsaicin (0.04% w/w) control patch (mean reduction in Numeric Pain Rating Scale score from baseline to Weeks 2–12; −27.0% vs −15.7%; p = 0.003). After application of the high-concentration capsaicin patch, significant pain reduction was apparent by Week 2 and this was maintained throughout the 12-week assessment period. In addition, significantly more patients responded to the high-concentration capsaicin patch than to control across other endpoints measured. Pain relief was evident regardless of concomitant pain medication and antiretroviral therapy. As the high-concentration capsaicin patch was also well tolerated, with only transient, localized application site-related reactions, these clinical data indicate that the high-concentration capsaicin patch could provide a promising new treatment for painful HIV-AN. High-concentration capsaicin in HIV-associated neuropathy: Clinical evidence and casesDavid M. Simpson10.1016/S1754-3207(10)70528-9European Journal of Pain Supplements 4, 2 (2010)2010-08-01European Journal of Pain Supplements2010-08-0142S1754-3207(10)X0003-7166169http://www.europeanjournalpainsupplements.com/article/PIIS1754320710705290/abstract?rss=yesSUMMARY: Post-herpetic neuralgia (PHN) is a common complication of shingles, but current therapies often only provide partial pain relief in a proportion of patients treated. Results of six randomized controlled studies in patients with PHN have demonstrated the efficacy and safety of a high-concentration capsaicin (8% w/w) (NGX-4010; QUTENZA™) patch following a single 60-minute application. Patients treated with capsaicin achieved greater pain relief during Weeks 2–8 and Weeks 2–12 compared with a 0.04% w/w capsaicin control patch in two pivotal Phase III studies. In the first study the mean percentage change in Numeric Pain Rating Scale score for Weeks 2–8 was −29.6% versus −19.9% (p = 0.01) for the high-concentration capsaicin patch versus control, respectively. This result was confirmed by a second similar study. Patients also reported a significant improvement in quality of life on the Patient Global Impression of Change following a single 60-minute application. An integrated analysis further demonstrated the efficacy of the high-concentration capsaicin patch and confirmed its good safety and tolerability profile. Sensory testing showed little or no effect on light brush, pinprick or warmth sensations following treatment and a slight improvement in vibration sensation. An open-label study that administered repeated applications of the high-concentration capsaicin patch over 1 year demonstrated its long-term safety with no increased incidence or severity of adverse events and no impact on neurologic function. The high-concentration capsaicin patch was well tolerated and the most common adverse events were application site-related, mild to moderate, and transient. High-concentration capsaicin for the treatment of post-herpetic neuralgia and other types of peripheral neuropathic painMiroslav M. Backonja10.1016/S1754-3207(10)70529-0European Journal of Pain Supplements 4, 2 (2010)2010-08-01European Journal of Pain Supplements2010-08-0142S1754-3207(10)X0003-7170174