Psychophysics/hyperalgesia: Stimulus-specific effects of intradermal capsaicin and non-painful thermal stimuli

Abstract

Pharmacological studies on distinct pain mechanisms are essential for more focalized patient care. Intradermal capsaicin produces pain, hyperalgesia, and flare, but elicited pain to different stimuli in capsaicin-sensitized skin is not well characterized. In addition, non-painful heat (40°C, 5 minutes each hour) has the potential to rekindle capsaicin's effects. To quantify elicited pain scores and assess whether non-painful heat modulates capsaicin-mediated effects, a randomized, crossover study was conducted with healthy volunteers (n=19) at UCSD's Center for Pain and Palliative Medicine. At .25, 1, 2, 3, and 4 hours after injection, spontaneous pain and elicited pain to von Frey, stroking (foam brush), and heat probe (40°C, 5 seconds) were recorded on a Visual Analog Scale (VAS) from 0-100, as were areas of flare and hyperalgesia to von Frey/stroking (cm2). Data were analyzed via 2-factor repeated measures ANOVA, revealing significantly greater elicited VAS to von Frey (F=14.2, p=.005, df=1,8), stroking (F=8.33, p=.020, df=1,8), and heat (F=11.0, p=.016, df=1,6), compared to spontaneous VAS. Follow-up comparisons (Bonferroni-corrected) showed significantly greater von Frey VAS at all 5 time points, stroking VAS at .25 and 1 hour, and heat VAS at .25 and 3 hours (p<.01). Heat lamp augmented spontaneous pain scores, evidenced by a significant rekindling by time interaction (F=6..01, p=.003, df=3,24) after square root transformation to adjust for heterogeneity of variance. There were minimal effects on elicited pain measures and areas of hyperalgesia, though heat lamp apparently attenuated elicited pain to direct-contact heat (F=4..99, p=.047, df=1,11) and augmented area of stroking hyperalgesia at 1 hour (F=11.1, p=.001, df=1,17). As all three elicited pain scores are significantly greater than spontaneous pain scores, they may be used as primary outcomes when testing analgesics. This study validates the use of intradermal capsaicin to induce component-specific mechanisms of pain sensation, facilitating analgesic efficacy studies targeting these distinct mechanisms.