Analysis of meaningful conditioned pain modulation effect in a pain-free adult population

Conditioned pain modulation (CPM) deals the effects of inhibitory and facilitatory pain modulatory systems and is inefficient in some chronic pain states. A proportion of healthy subjects also exhibit little or no CPM, perhaps indicating that inherent factors such as gender or genetics may be influential. However there is no consensus on how best to determine meaningful CPM effect. This study attempted to determine the proportion of pain-free subjects exhibiting a meaningful CPM effect. Analyses of associations between serotonin transporter polymorphisms (5HTTLPR), gender and CPM effect were also carried out. 125 healthy subjects (47 male; 78 female) underwent pressure-pain threshold (PPT) testing before, during, and after a cold pressor conditioning stimulus. A buccal cell sample was collected for analysis of 5HTTLPR genotype. Meaningful CPM effect was determined as an increase in PPT values from baseline greater than the inherent error of measurement, calculated as 5.3%. During the conditioning stimulus, 115 subjects (92%) exhibited a CPM effect while 10 did not. CPM effect did not vary significantly between genders or between 5HTTLPR genotypes. This provides a clear basis on which to determine the proportion of patients with a chronic pain disorder that display a meaningful CPM effect.

This study proposes a method for calculating meaningful CPM effect and reports the proportion and magnitude of effect elicited in a large sample. Associations between CPM, gender and genotype were also analyzed. Clarification of normal CPM response may help to improve understanding of the mechanisms driving CPM inefficiency in chronic pain.