<p>Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification</p>

Abstract

Purpose Chemotherapy-induced peripheral neuropathy (CIPN) with associated chronic pain is a common and disabling condition. Current treatments for neuropathic pain in CIPN are largely ineffective, with unfavorable side-effects. The capsaicin 8% patch (capsaicin 179 mg patch) is approved for the treatment of neuropathic pain: a single topical cutaneous application can produce effective pain relief for up to 12 weeks. We assessed the therapeutic potential of capsaicin 8% patch in patients with painful CIPN, and its mechanism of action. Patients and methods 16 patients with chronic painful CIPN (mean duration 2.5 years), in remission for cancer and not receiving chemotherapy, were treated with 30 min application of capsaicin 8% patch to the feet. Symptoms were monitored using the 11-point numerical pain rating scale (NPRS), and questionnaires. Investigations were performed at baseline and three months after patch application, including skin biopsies with a range of markers, and quantitative sensory testing (QST). Results Patients reported significant reduction in spontaneous pain (mean NPRS: −1.27; 95% CI 0.2409 to 2.301; p =0.02), touch-evoked pain (−1.823; p =0.03) and cold-evoked pain (−1.456; p =0.03). Short-Form McGill questionnaire showed a reduction in neuropathic ( p =0.0007), continuous ( p =0.01) and overall pain ( p =0.004); Patient Global Impression of Change showed improvement ( p =0.001). Baseline skin biopsies showed loss of intra-epidermal nerve fibers (IENF), and also of sub-epidermal nerve fibers quantified by image analysis. Post-patch application skin biopsies showed a significant increase towards normalization of intra-epidermal and sub-epidermal nerve fibers (for IENF: structural marker PGP9.5, p =0.009; heat receptor TRPV1, p =0.027; regenerating nerve marker GAP43, p =0.04). Epidermal levels of Nerve Growth Factor (NGF), Neurotrophin-3 (NT-3), and Langerhans cells were also normalized. QST remained unchanged and there were no systemic side-effects, as in previous studies. Conclusion Capsaicin 8% patch provides significant pain relief in CIPN, and may lead to regeneration and restoration of sensory nerve fibers ie, disease modification.

Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice

“…The coexistence of sensory fiber loss with neuropathic pain and the capacity of interventions that promote neuroprotection and regeneration of fibers to alleviate indices of pain has also been reported in animals and humans with diabetic peripheral neuropathy (42) and chemotherapy-induced peripheral neuropathy (82,83). A recent study has shown that gut bacteria eradication by a longer antibiotic treatment paradigm prevented development of mechanical hyperalgesia in a model of chemotherapy-induced pain (30).…”

Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity

“…In our study, this assessment allows the pathological confirmation of the behavioral test results, providing them with a strong and reliable support, but it is also important since IENF density measurement is used in the clinical setting, making the translation of the preclinical results much easier and more reliable [ 26 ]. Furthermore, there are examples of clinical treatment effects with pharmacological agents that correlate with the reversal of IENF reduction [ 27 ].…”

Recent advances in understanding chemotherapy-induced peripheral neuropathy

“…A small non-randomised study of topical menthol in 52 patients showed improved BPI scores 126 , and combination therapy with baclofen, amitriptyline and ketamine showed an improvement on some of the EORTC QLQ-CIPN-20 measures 127 . Topical 8% capsaicin patch application following CIPN has been shown to improve continuous pain, neuropathic pain symptoms, and patient global impression of change 128 . This treatment has also been found to improve IENF density, suggesting underlying disease modification 128 .…”