Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

Abstract

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration

“…This was accompanied, as studied in CIPN, by an improvement in a range of other mechanistic biomarkers i.e., epidermal levels of Nerve Growth Factor (NGF), Neurotrophin-3 (NT-3), and Langerhans cells ( 22 ). Capsaicin 8% patch (Qutenza) treatment in non-freezing cold injury (NFCI) also led to pain relief and nerve regeneration; pain relief correlated with restoration of nerve fibers ( 23 ). However, there are some differences between our previous painful CIPN / NFCI and current DPN studies with capsaicin 8% patch (Qutenza).…”

“…In clinical treatment combined with tissue studies, capsaicin 8% patch (Qutenza) application for post-herniorrhaphy neuropathic pain did not lead to significant pain relief or change of IENFs in skin biopsies from the site of surgery ( 21 ). In painful chemotherapy-induced peripheral neuropathy (CIPN), capsaicin 8% patch (Qutenza) application to the feet and distal calf led to a reduction of pain, along with a significant increase of intra-epidermal and sub-epidermal nerve fibers in distal calf skin biopsies, and improvement in other mechanistic biomarkers ( 22 , 23 ). Capsaicin 8% patch (Qutenza) treatment in non-freezing cold injury (NFCI) also led to pain relief and nerve regeneration; importantly, pain relief correlated with restoration of nerve fibers ( 23 ), in support of our proposed mechanism of “disease-modification” ( 22 , 23 ).…”

Capsaicin treatment in neuropathic pain: axon reflex vasodilatation after 4 weeks correlates with pain reduction

“…3,29 Furthermore, recent studies indicate that the application of capsaicin in patients with chemotherapy-induced neuropathy and chronic nonfreezing cold injury might initiate a de novo axon growth and regeneration as measured in skin biopsies before and 12 weeks after the treatment. 1,2 This capsaicininduced regeneration of nociceptors was associated with significant pain reduction. These observations suggest that the initial effect of topically applied capsaicin, that is, a defunctionalization and degeneration of nerve fibers, is not the decisive mechanism of action of capsaicin treatment.…”

Can iloprost be used for treatment of cold weather injury at the point of wounding in a forward operating environment? A literature review

“…To that end, Anand et al . have considered the use of novel topical therapies such as capsaicin in the NFCI population to good effect [ 42 ]. These patients showed good response to single treatment topical application but were all known to have established disease and had not received treatment at the point of wounding.…”