My call: capsaicin cream is the only treatment here with any evidence of supporting nerve regrowth, and that evidence is modest and conflicted. elaborate

The short version: the evidence for capsaicin cream supporting nerve regrowth is modest, conflicted, and comes from manufacturer-funded trials with small biopsy substudies.

The mechanism is plausible. Capsaicin desensitizes TRPV1 nerve endings, which causes a temporary die-back of those fibers. The body then regenerates them. A 2025 review reports that after high-concentration capsaicin treatment, regenerating fibers appear around three weeks, with fuller regrowth over 12 to 24 weeks [1]. A single-center trial found increased epidermal nerve fiber density on biopsy at three months [1]. That is the only direct regrowth evidence in this retrieval.

But the larger trials were funded by the manufacturer. The PACE trial, a Phase III safety study, used quality of life as its primary endpoint, not nerve regrowth [1]. The biopsy evidence comes from small, single-center studies. The post-hoc analysis showing 77 in 100 people got pain relief after seven applications is a subgroup analysis of a trial not designed to measure regrowth [1]. The CASPAR real-world data is observational, not randomized [1].

The evidence does not include a single trial that compared treated to untreated patients over years with repeat skin biopsies. That is the study design that would actually settle whether capsaicin reverses small fiber loss. It has not been run.

My call: capsaicin cream has the most evidence of any treatment in this retrieval for supporting nerve regrowth, but that evidence is modest, conflicted, and comes from manufacturer-funded trials with small biopsy substudies. Confidence: low.