Topical capsaicin produces secondary mechanical hyperalgesia without a group-level increase in tonic heat pain summation in healthy adults.

Abstract

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-wk 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 used weighted pinprick (256 mN, 16 stimuli, 1 Hz) and was quantified using Sumscore. Outcomes were measured at baseline, 10-, 20-, and 30-min postintervention. Secondary mechanical hyperalgesia was induced postcapsaicin, 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 time point 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 postcapsaicin 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 interindividual variability observed in this exploratory within-subject analysis was not statistically significant and is hypothesis generating.NEW & NOTEWORTHY This is, to our knowledge, the first double-blind, placebo-controlled, crossover study to quantify temporal summation of heat pain within regions of secondary hyperalgesia using an extended tonic thermal stimulus. Capsaicin-induced central sensitization produced significant secondary mechanical hyperalgesia without a statistically significant group-level increase in tonic heat summation. The findings describe a modality-specific pattern under this protocol and should not be interpreted as proof that thermal sensitization is absent.