The dynamics of pain: evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain

Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous systems. 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 versus 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 2 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 2 adaptation processes, one site-specific and the other 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 2 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.