Topical Capsaicin Produces Secondary Mechanical Hyperalgesia Without a Group-Level Increase in Tonic Heat Pain Summation in Healthy Adults.

Central sensitization can produce secondary mechanical hyperalgesia; however, secondary thermal hyperalgesia remains controversial. This study investigated whether topical capsaicin alters temporal summation to tonic heat-pain within regions of secondary mechanical hyperalgesia. Twenty-six healthy adults (19 women, 7 men; 22.5 ± 3.5 yr) completed a participant- and investigator-masked, placebo-controlled, crossover protocol (≥1-week washout) with topical capsaicin (0.075% Zostrix) or placebo (Lubriderm) applied to C5-C6 dermatomes. Temporal summation to tonic heat-pain was assessed at 46.5°C for 120 s and quantified as the area under the pain-time curve (AUC). Mechanical summation employed weighted pinprick (256 mN, 16 stimuli, 1 Hz) and quantified using Sumscore. Outcomes were measured at baseline, 10-, 20-, and 30-min post-intervention. Secondary mechanical hyperalgesia was induced post-capsaicin, with a significant main effect of intervention (F[1,24]=4.77, p=0.039); the main effect of time and the time*intervention interaction were not significant, and no individual timepoint comparison survived multiplicity adjustment. Temporal summation to tonic heat-pain within secondary hyperalgesic regions showed no significant effects of time, intervention or time*intervention (p>0.05). Within-subject analysis revealed 18/26 participants (69%; 95%CI: 0.48 to 0.86) with higher peak thermal AUC post-capsaicin versus placebo (two-sided p=0.076), but exhibiting substantial individual heterogeneity. Topical capsaicin-induced central sensitization produced significant secondary mechanical hyperalgesia but no statistically significant group-level increase in temporal summation of heat-pain. This modality-specific pattern using the current protocol does not exclude a moderate thermal effect. The substantial inter-individual variability observed in this exploratory within-subject analysis was not statistically significant and is hypothesis-generating.