# Response to High‐Dose Topical Capsaicin in Neuropathic Pain: Absence of Deep Pain as a Predictor of Analgesic Effect

## TL;DR

This study finds that psychological and sensory factors, along with a specific genetic variant, predict how well high-dose capsaicin relieves neuropathic pain.

## Contribution

The study introduces new predictors of capsaicin treatment response, including psychological, sensory, and genetic factors.

## Key findings

- Higher pain catastrophizing is the strongest predictor of capsaicin treatment response.
- Sensory parameters like vibration and pressure pain thresholds also predict treatment effectiveness.
- A TRPV1 genetic variant (rs222747) significantly influences pain relief from capsaicin.

## Abstract

Topical high‐dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non‐interventional exploratory study was to improve prediction of treatment response to high‐dose capsaicin by including quantifiable parameters and standardised questionnaires.

Forty‐eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient‐reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser‐speckle‐contrast‐analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO‐synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).

Patient‐reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.

A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high‐dose capsaicin treatment and provide promising targets for future investigation.

This exploratory study identifies promising predictors for analgesic response to high‐concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve‐fibre assessments and genetic polymorphisms.