Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous system. Somewhat paradoxically, repeated stimulation can produce an increase (sensitization) or a decrease (habituation) in pain. Adaptation processes may also be body-site-specific or operate across body sites, and considering this distinction may help explain the conditions under which habituation vs. sensitization occurs. To dissociate the effects of site-specific and site-nonspecific adaptation processes, we examined reported pain in 100 participants during counterbalanced sequences of noxious thermal stimulation on multiple skin sites. Analysis of pain ratings revealed two opposing sequential effects: repeated stimulations of the same skin site produced temperature-dependent habituation, whereas repeated stimulations across different sites produced sensitization. Stimulation trials were separated by ~20 seconds and sensitization was unrelated to the distance between successively stimulated sites, suggesting that neither temporal nor spatial summation occurred. To explain these effects, we propose a dynamic model with two adaptation processes, one site-specific and one site-nonspecific. The model explains 93% of the variance in the group-mean pain ratings after controlling for current stimulation temperature, with its estimated parameters showing evidence for habituation for the site-specific process and sensitization for the site-nonspecific process. The two pain-adaptation processes revealed in this study, and the ability to disentangle them, may hold keys to understanding multiple pain-regulatory mechanisms and their disturbance in chronic-pain syndromes.
Perspective
This article presents novel evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain, which can be disentangled (and the direction and strength of each process estimated) by a dynamic model. The dissociation of site-specific and site-nonspecific adaptation processes may hold keys to understanding multiple pain-regulatory mechanisms in both healthy and patient populations.