Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers.

Responses to capsaicin are reduced following repeated exposure, a phenomenon known as capsaicin desensitization. Heavy consumers of chilies consistently report reduced oral burn relative to infrequent consumers, presumably due to chronic desensitization. However, the mechanism(s) underlying capsaicin desensitization remain poorly understood. We hypothesized that reduced response to capsaicin due to repeated oral exposure may result from a change in the expression of the capsaicin receptor (TRPV1) gene. To test this, we conducted two longitudinal desensitization studies in healthy human volunteers. In Study 1, 51 adults completed a 17-day capsaicin desensitization protocol. The study consisted of three in-person visits where they were asked to sample stimuli, including 3, 6, and 9 ppm capsaicin, and rate intensity on a general labeled magnitude scale (gLMS). Between days 3 & 17, participants rinsed at home with 6 ppm capsaicin (n = 31) or a control (n = 20) solution (20 uM sucrose octaccetate; SOA) twice a day. Before and after the oral exposure protocol, a clinician collected fungiform papillae. Participants randomized to the capsaicin rinse showed a statistically significant reduction in oral burn ratings that was not observed in controls, indicating repeated low-dose exposure can systematically induce desensitization. TRPV1 expression was not associated with reported capsaicin burn, and there was no evidence of a decrease in TRPV1 expression following capsaicin exposure. In Study 2, participants (n = 45) rinsed with 6 ppm capsaicin in a similar protocol, rating capsaicin, vanillyl butyl ether (VBE), cinnamaldehyde, ethanol, menthol, and sucrose on days 1, 3, & 17. Burn from capsaicin, VBE, cinnamaldehyde, and ethanol all showed a statistically significant change - capsaicin, VBE and cinnamaldehyde burn all dropped ∼20 %, and a larger reduction was seen for ethanol - while menthol cooling and sucrose sweetness did not change. Collectively, this suggests reductions in oral burn following chronic capsaicin exposure generalizes to other stimuli (i.e., cross desensitization) and this cannot be explained by a change in TRPV1 mRNA expression. More work is needed to elucidate the underlying mechanism for capsaicin desensitization in the oral cavity.

Putting out the fire - Efficacy of common beverages in reducing oral burn from capsaicin.

Capsaicin is classically considered an irritant, due to the warming and burning sensations it elicits. Widespread consumption of chilis suggests many individuals enjoy this burn, but these sensations can be overwhelming if the burn is too intense. While substantial folklore exists on the ability of specific beverages to mitigate capsaicin burn, quantitative data to support these claims are generally lacking. Here, we systematically tested various beverages for their ability to reduce oral burn following consumption of capsaicin in tomato juice. Participants (n = 72, 42 women, 30 men) rated the burn of 30 mL of spicy tomato juice on a general Labeled Magnitude Scale (gLMS) immediately after swallowing, and again every 10 s for 2 min. On 7 of 8 trials, a test beverage (40 mL) was consumed after tomato juice was swallowed, including: skim milk, whole milk, seltzer water, Cherry Kool-Aid, non-alcoholic beer, cola, and water. Participants also answered questions regarding intake frequency and liking of spicy food. Initial burn of tomato juice alone was rated below "strong" but above "moderate" on a gLMS and continued to decay over the 2 min to a mean just above "weak". All beverages significantly reduced the burn of the tomato juice. To quantify efficacy over time, area under the curve (AUC) values were calculated, and the largest reductions in burn were observed for whole milk, skim milk, and Kool-Aid. More work is needed to determine the mechanism(s) by which these beverages reduce burn (i.e., partitioning due to fat, binding by protein, or sucrose analgesia). Present data suggest milk is the best choice to mitigate burn, regardless of fat context, suggesting the presence of protein may be more relevant than lipid content.