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Published in: Pain and Therapy 2/2014

Open Access 01-12-2014 | Review

High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know

Authors: Nurcan Üçeyler, Claudia Sommer

Published in: Pain and Therapy | Issue 2/2014

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Abstract

Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza®; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs.
Appendix
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Literature
1.
go back to reference Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.PubMedCrossRef Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.PubMedCrossRef
2.
go back to reference Haanpaa M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011;152:14–27.PubMedCrossRef Haanpaa M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011;152:14–27.PubMedCrossRef
3.
go back to reference Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9:807–19.PubMedCrossRef Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9:807–19.PubMedCrossRef
4.
go back to reference Dib-Hajj SD, Rush AM, Cummins TR, et al. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain. 2005;128:1847–54.PubMedCrossRef Dib-Hajj SD, Rush AM, Cummins TR, et al. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain. 2005;128:1847–54.PubMedCrossRef
5.
go back to reference Tominaga M. Nociception and TRP channels. Handb Exp Pharmacol. 2007:489–505. Tominaga M. Nociception and TRP channels. Handb Exp Pharmacol. 2007:489–505.
6.
go back to reference Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol. 2010;229:26–50.PubMedCrossRef Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol. 2010;229:26–50.PubMedCrossRef
7.
go back to reference Hagenacker T, Czeschik JC, Schafers M, Busselberg D. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-alpha. Brain Res Bull. 2010;81:157–63.PubMedCrossRef Hagenacker T, Czeschik JC, Schafers M, Busselberg D. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-alpha. Brain Res Bull. 2010;81:157–63.PubMedCrossRef
8.
go back to reference Kochukov MY, McNearney TA, Yin H, et al. Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain. 2009;5:49.PubMedCentralPubMedCrossRef Kochukov MY, McNearney TA, Yin H, et al. Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain. 2009;5:49.PubMedCentralPubMedCrossRef
9.
go back to reference Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816–24.PubMedCrossRef Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816–24.PubMedCrossRef
10.
go back to reference Baron R. Pharmakologische nicht-interventionelle Therapie chronisch neuropathischer Schmerzen. In: Diener HC, Weimar C, editors. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme; 2012. p. 771–83. Baron R. Pharmakologische nicht-interventionelle Therapie chronisch neuropathischer Schmerzen. In: Diener HC, Weimar C, editors. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme; 2012. p. 771–83.
11.
go back to reference Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain—consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12:13–21.PubMedCentralPubMed Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain—consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12:13–21.PubMedCentralPubMed
12.
go back to reference Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17:1113–e1188.PubMedCrossRef Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17:1113–e1188.PubMedCrossRef
13.
go back to reference Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132:237–51.PubMedCrossRef Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132:237–51.PubMedCrossRef
14.
go back to reference Jensen TS, Madsen CS, Finnerup NB. Pharmacology and treatment of neuropathic pains. Curr Opin Neurol. 2009;22:467–74.PubMedCrossRef Jensen TS, Madsen CS, Finnerup NB. Pharmacology and treatment of neuropathic pains. Curr Opin Neurol. 2009;22:467–74.PubMedCrossRef
15.
go back to reference Harden N, Cohen M. Unmet needs in the management of neuropathic pain. J Pain Symptom Manag. 2003;25:S12–7.CrossRef Harden N, Cohen M. Unmet needs in the management of neuropathic pain. J Pain Symptom Manag. 2003;25:S12–7.CrossRef
16.
go back to reference Treede RD, Wagner T, Kern KU, et al. Mechanism- and experience-based strategies to optimize treatment response to the capsaicin 8% cutaneous patch in patients with localized neuropathic pain. Curr Med Res Opin. 2013;29:527–38.PubMedCrossRef Treede RD, Wagner T, Kern KU, et al. Mechanism- and experience-based strategies to optimize treatment response to the capsaicin 8% cutaneous patch in patients with localized neuropathic pain. Curr Med Res Opin. 2013;29:527–38.PubMedCrossRef
17.
go back to reference Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998;18:8947–59.PubMed Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998;18:8947–59.PubMed
18.
go back to reference Kennedy WR, Vanhove GF, Lu SP, et al. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010;11:579–87.PubMedCrossRef Kennedy WR, Vanhove GF, Lu SP, et al. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010;11:579–87.PubMedCrossRef
19.
go back to reference Goswami C, Schmidt H, Hucho F. TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization. FEBS J. 2007;274:760–72.PubMedCrossRef Goswami C, Schmidt H, Hucho F. TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization. FEBS J. 2007;274:760–72.PubMedCrossRef
20.
21.
go back to reference Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC. Natural history of cutaneous innervation following herpes zoster. Pain. 2010;150:75–82.PubMedCrossRef Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC. Natural history of cutaneous innervation following herpes zoster. Pain. 2010;150:75–82.PubMedCrossRef
22.
go back to reference Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002;36:57–68.PubMedCrossRef Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002;36:57–68.PubMedCrossRef
23.
24.
go back to reference Bowles WR, Sabino M, Harding-Rose C, Hargreaves KM. Chronic nerve growth factor administration increases the peripheral exocytotic activity of capsaicin-sensitive cutaneous neurons. Neurosci Lett. 2006;403:305–8.PubMedCrossRef Bowles WR, Sabino M, Harding-Rose C, Hargreaves KM. Chronic nerve growth factor administration increases the peripheral exocytotic activity of capsaicin-sensitive cutaneous neurons. Neurosci Lett. 2006;403:305–8.PubMedCrossRef
25.
go back to reference Kim JH, Ko JA, Kim JT, et al. Preparation of a capsaicin-loaded nanoemulsion for improving skin penetration. J Agric Food Chem. 2014 [Epub ahead of Print]. Kim JH, Ko JA, Kim JT, et al. Preparation of a capsaicin-loaded nanoemulsion for improving skin penetration. J Agric Food Chem. 2014 [Epub ahead of Print].
26.
go back to reference Ständer S, Moormann C, Schumacher M, et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol. 2004;13:129–39.PubMedCrossRef Ständer S, Moormann C, Schumacher M, et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol. 2004;13:129–39.PubMedCrossRef
29.
go back to reference Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106–12.PubMedCrossRef Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106–12.PubMedCrossRef
30.
go back to reference Backonja MM, Malan TP, Vanhove GF, Tobias JK, Group CS. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension. Pain Med. 2010;11:600–8.PubMedCrossRef Backonja MM, Malan TP, Vanhove GF, Tobias JK, Group CS. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension. Pain Med. 2010;11:600–8.PubMedCrossRef
31.
go back to reference Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12:99–109.PubMedCrossRef Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12:99–109.PubMedCrossRef
32.
go back to reference Webster LR, Malan TP, Tuchman MM, Mollen MD, Tobias JK, Vanhove GF. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. J Pain. 2010;11:972–82.PubMedCrossRef Webster LR, Malan TP, Tuchman MM, Mollen MD, Tobias JK, Vanhove GF. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. J Pain. 2010;11:972–82.PubMedCrossRef
33.
go back to reference Clifford DB, Simpson DM, Brown S, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. 2012;59:126–33.PubMedCrossRef Clifford DB, Simpson DM, Brown S, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. 2012;59:126–33.PubMedCrossRef
34.
go back to reference Simpson DM, Brown S, Tobias J, Group N-CS. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70:2305–13.PubMedCrossRef Simpson DM, Brown S, Tobias J, Group N-CS. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70:2305–13.PubMedCrossRef
35.
go back to reference Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. The Cochrane Database of Systematic Reviews. 2013;2:CD007393. Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. The Cochrane Database of Systematic Reviews. 2013;2:CD007393.
37.
go back to reference Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Efficacy of Qutenza(R) (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154:1632–9.PubMedCrossRef Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Efficacy of Qutenza(R) (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154:1632–9.PubMedCrossRef
38.
go back to reference Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Qutenza (Capsaicin) 8% patch onset and duration of response and effects of multiple treatments in neuropathic pain patients. Clin J Pain. 2014;30:286–94.PubMedCrossRef Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Qutenza (Capsaicin) 8% patch onset and duration of response and effects of multiple treatments in neuropathic pain patients. Clin J Pain. 2014;30:286–94.PubMedCrossRef
39.
go back to reference Maihöfner C, Heskamp ML. Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous patch in 1,044 patients with peripheral neuropathic pain: first results of the QUEPP study. Curr Med Res Opin. 2013;29:673–83.PubMedCrossRef Maihöfner C, Heskamp ML. Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous patch in 1,044 patients with peripheral neuropathic pain: first results of the QUEPP study. Curr Med Res Opin. 2013;29:673–83.PubMedCrossRef
40.
go back to reference Brown S, Simpson DM, Moyle G, et al. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Res Ther. 2013;10:5.PubMedCentralPubMedCrossRef Brown S, Simpson DM, Moyle G, et al. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Res Ther. 2013;10:5.PubMedCentralPubMedCrossRef
41.
go back to reference Maihöfner CG, Heskamp ML. Treatment of peripheral neuropathic pain by topical capsaicin: impact of pre-existing pain in the QUEPP-study. Eur J Pain. 2014;18:671–9.PubMedCentralPubMedCrossRef Maihöfner CG, Heskamp ML. Treatment of peripheral neuropathic pain by topical capsaicin: impact of pre-existing pain in the QUEPP-study. Eur J Pain. 2014;18:671–9.PubMedCentralPubMedCrossRef
42.
go back to reference Martini CH, Yassen A, Krebs-Brown A, et al. A novel approach to identify responder subgroups and predictors of response to low- and high-dose capsaicin patches in postherpetic neuralgia. Eur J Pain. 2013;17:1491–501.PubMed Martini CH, Yassen A, Krebs-Brown A, et al. A novel approach to identify responder subgroups and predictors of response to low- and high-dose capsaicin patches in postherpetic neuralgia. Eur J Pain. 2013;17:1491–501.PubMed
Metadata
Title
High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know
Authors
Nurcan Üçeyler
Claudia Sommer
Publication date
01-12-2014
Publisher
Springer Healthcare
Published in
Pain and Therapy / Issue 2/2014
Print ISSN: 2193-8237
Electronic ISSN: 2193-651X
DOI
https://doi.org/10.1007/s40122-014-0027-1