Temporal characteristics of capsaicin desensitization and stimulus-induced recovery in the oral cavity

It was recently discovered that capsaicin desensitization of the tongue can be temporarily reversed during recurrent stimulation ("stimulus-induced recovery," SIR). The effects of concentration and the temporal pattern of stimulation on desensitization and SIR were studied in four experiments. In Experiment 1, three different concentrations of capsaicin (3.3, 33, or 330 microM) were delivered to the tongue in blocks of twelve stimuli at the rate of one per minute (treatment block) followed by a block of 20 exposures to 33 microM capsaicin (test block). The 33- and 330-microM treatments both caused significant desensitization, but by the end of the test block recovery was substantial only for the 33-microM condition. Experiment 2 provided a second test of the effect of concentration while also exploring whether intermittent stimulation was a requirement for SIR, i.e., stimuli were refreshed on the tongue every six minutes rather than every 60 s. SIR occurred but was pronounced only when the concentration of the test stimulus equaled or exceeded that of the treatment stimulus. In the third experiment we delivered capsaicin in a candy formulation to examine SIR under conditions in which stimulation was not interrupted at all. Although desensitization was evident during the first few minutes of succeeding exposures to the candy, peak irritation was unchanged throughout nine exposures over 3 days. In the final experiment, we returned to intermittent stimulation to examine the effect of lengthening ISI on SIR. The results showed that SIR remained virtually complete until ISI was lengthened to 60 s. We conclude that SIR is a robust phenomenon that is maximized by rapid exposure to capsaicin in a concentration at least as high as that of the desensitizing stimulus. The implications of these findings for hypotheses about the mechanism of SIR, its function in endogenous chemonociception, and for clinical use of capsaicin as a topical analgesic are discussed.