Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial

Background: Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. Objective: To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Design: Randomized, placebo-controlled, double-blind clinical trial. Setting: Outpatient pain clinic. Participants: Twenty-five adults with pain-free lips. Methods: Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Outcome Measures: Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Results: Participants reached a capsaicin-induced pain level of 7.8 +/- 1.0 points in 3.3 +/- 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P <. 05) and in AUC analysis (P < .001). Conclusions: Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect.