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Papers of the Week

Papers: 16 Jul 2022 - 22 Jul 2022

2022 Jul 20


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


Sendel M, Dunst A, Forstenpointner J, Hüllemann P, Baron R
Pain. 2022 Jul 20.
PMID: 35857438.


Capsaicin, an agonist at the transient receptor potential vanilloid 1, is used for the topical treatment of peripheral neuropathic pain. Reversible receptor defunctionalization and degeneration and subsequent regeneration of cutaneous nociceptors are discussed as its mechanism of action. Here, we hypothesize an accelerated functional recovery of a sub-class of nociceptive afferents, the peptidergic vasoactive nociceptors, as the potential cause of capsaicin analgesia.In this non-interventional exploratory trial, 23 patients with peripheral neuropathic pain were treated with one topical high-concentration capsaicin application. Baseline pain ratings, co-morbidities and quality-of-life were assessed. Functional laser-speckle-contrast-analysis (fLASCA, heat-evoked neurogenic vasodilatation to assess functional properties of peptidergic nociceptors) and quantitative sensory testing (QST) were performed in the affected skin. Four weeks after treatment fLASCA and questionnaires were repeated. Telephone interviews were conducted at week 2, 10 and 12.Topical capsaicin treatment induced a significant reduction of pain intensity with a maximum at four weeks. At the same time, heat-evoked neurogenic vasodilatation was on average similar to pre-treatment values. Half of the patients not only showed a functional recovery but also an improvement of vasodilatation, indicating regeneration of nerve fibers. Patients with improved heat-evoked neurogenic vasodilatation at week 4 showed a greater pain reduction than patients with deterioration. The degree of vasodilatation significantly correlated with pain reduction.These findings suggest that (i) regeneration of peptidergic nociceptors may be one mechanism of capsaicin-induced analgesia and (ii) that a disease-modifying effect of capsaicin on these fibers already occurs four weeks after application.