The Acute Effect of Skin Preheating on Capsaicin‐Induced Central Sensitization in Humans

Introduction Topical capsaicin is commonly employed to experimentally induce central sensitization (CS) in humans. While previous studies have investigated the effect of skin preheating on the sensitizing effect of capsaicin, no studies have compared the synergistic effect of skin preheating on the magnitude of sensitization via topical capsaicin within the first 30 minutes of application. We tested the hypothesis that skin preheating potentiates the sensitizing effect of topical capsaicin by evoking a larger region of secondary hyperalgesia vs. topical capsaicin alone. Methods Twenty young, healthy subjects each received topical capsaicin (Zostrix HP 0.075%) only (CAP), topical capsaicin with preheating (CAP + HEAT), and topical nonsensitizing placebo cream (CON) in a crossover design. Capsaicin and placebo creams were applied to a 50 cm2 area of the dorsal forearm. The CAP + HEAT session also included a 10‐minute preheating session. Regions of secondary hyperalgesia were assessed using mechanical brush allodynia testing, and skin temperature was assessed via infrared thermography. Outcomes were normalized to baseline and compared at 10, 20, and 30 minutes after cream application. Results The CAP + HEAT session led to a significantly larger area of secondary hyperalgesia compared to the CAP session as measured by brush allodynia (CON: 0 ± 0 cm; CAP: 2.08 ± 0.45 cm; CAP + HEAT: 3.70 ± 0.46 cm; P