Targeting TRPV1 activity via high‐dose capsaicin in patients with sickle cell disease

Abstract

Evidence suggests neuropathic pain (NP) develops over time in sickle cell disease (SCD), contributing to a complex, difficult-to-treat phenotype, with management based on scant evidence. One characteristic of NP found is hyperalgesia caused by nervous system sensitization, but risk factors for this have not been identified within the SCD population, as exact mechanisms leading to its development are not well defined.The SPICE (Sickle cell Pain: Intervention with Capsaicin Exposure) trial was a pilot safety and feasibility trial of high-dose (8%) topical capsaicin for patients with SCD and recurrent/chronic pain with neuropathic features, aimed at exploring capsaicin's utility as a mechanistic probe and adjunctive pain treatment for this population. Ten participants identifying "target" sites of pain with NP-type qualities consented to treatment. The primary endpoint was safety/tolerability. The novel Localized Peripheral Hypersensitivity Relief score (LPHR) was developed to determine improvement in sensitivity attributable to TRPV1 neutralization. There were no severe treatment-related adverse events. Higher baseline pain sensitivity at a given body site was associated with self-reported history of more frequent localized vaso-occlusive pain episodes at that site. There was a statistically significant improvement in the mean LPHR, evidencing TRPV1's importance to the development of hypersensitivity and a potential therapeutic benefit of capsaicin for SCD.

Capsaicin: A Novel Approach to the Treatment of Functional Dyspepsia

“…Repeated application of CAP for 10–14 days may permanently ablate C‐fibers of the whole body. [ 66 ] The destruction of 80–95% of afferent C‐fiber in the lumbar dorsal roots and permanent insensitivity of the TRPV1 receptor was observed after subcutaneous injection of CAP into newborn rats. [ 67 ] Various studies have investigated the pain response in CAP‐treated newborn rats.…”