Background & Aims
Treatment of neuropathic pain remains a challenge in everyday practice. Transdermal application of high-dose capsaicin is established as a recommended therapy in localized peripheral neuropathic pain with limited side effects. As an agonist of TRPV1 receptor, capsaicin can provide pain relief lasting up to months after a short application probably by degeneration and regeneration of nerve fibers. However, not all patients respond. Limited predictors such as age, gender, duration of pain or specific pain symptoms have been described so far. A possible association between improvement in heat-evoked neurogenic vasodilation and response to capsaicin as well as between genetic variants of TRPV1 receptor and capsaicin-induced changes in sensory function have been reported. The aim of this study was to identify additional predictors of response to capsaicin therapy by investigating standardized questionnaires, somatosensory phenotype, function of peptidergic nociceptors and genetic factors.
Methods
In total 48 capsaicin-naive patients with peripheral neuropathic pain scheduled to receive topical capsaicin therapy were included. Pain intensity and characteristics as well as quality of life and mental health were assessed before and up to 12 weeks after therapy using standardized questionnaires. To evaluate the function of peripheral TRPV1-positive C-fibers, heat-evoked neurogenic vasodilation in the affected skin was assessed via functional laser-speckle-contrast-analysis before and 4 weeks after therapy. Somatosensory function of different groups of peripheral nerve fibers and their central pathways was examined psychophysically at baseline using quantitative sensory testing. To investigate the potential influence of genetic variants, following single nucleotide polymorphisms were determined: TRPV1 1911A>G (rs8065080) plus 1103C>G (rs222747) and ENOS 894T>G (rs1799983). Improvement in pain after 4 weeks compared to baseline was used as the outcome measure for regression analyses.
Results
In the examined cohort (n=48), single treatment with 8% topical capsaicin resulted in a significant reduction in maximum pain intensity during the last 24 hours at all recorded time points (2, 4, 10 and 12 weeks) compared to baseline (up to p ? 0.01) and in significant improvement in quality of life after 4 weeks (p = 0.043). In the multivariate analysis, three parameters were significantly associated with pain reduction after 4 weeks: high pain catastrophizing (single most important predictor) as well as low perception of vibration and pressure pain. The prediction accuracy of the model reached 26.6%, while all three parameters individually reached statistical significance. When considering only the polymorphisms, just rs222747 in the TRPV1 gene showed a significant influence (p = 0.028) on pain relief with 13 – 26% prediction accuracy. The function of the vasoactive C-fibers could not be identified as a significant predictor for the outcome measures pain intensity or quality of life.
Conclusions
Several parameters were identified as predictors of the response to high-dose topical capsaicin. Patient-reported catastrophizing is found to be the most important predictor. In quantitative sensory testing, loss of vibration and pressure pain function were associated with better response. Thus, response to therapy seems to be higher when subcutaneous/ deep somatic afferents are less affected.
In addition, the single nucleotide polymorphism rs222747 in TRPV1 gene represents a genetic marker with high potential as a predictor of response to capsaicin and is therefore an interesting target for future investigations.
With the help of the model presented, a prediction accuracy of up to 26.6% can be achieved. Thus, some important patient-relevant predictors of the response to capsaicin therapy could be identified. In the future it will be necessary to identify further influencing factors and to refine the prediction model to further improve precision medicine.
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Presenting Author
Lena Ehmke
Poster Authors
Lena Ehmke
UKSH Kiel, Neurologische Schmerzforschung und -therapie
Lead Author
Manon Sendel
Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein
Lead Author
Andreas Dunst
Lead Author
Julia Forstenpointner
Division of Neurological Pain Research and Therapy, University Hospital Kiel
Lead Author
Jan Vollert
Pain Research, Department of Surgery and Cancer, Imperial College London
Lead Author
Philipp Hüllemann
Prof.
Lead Author
Ralf Baron
University Medical Center Schleswig-Holstein
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral