Analysis of Meaningful Conditioned Pain Modulation Effect in a Pain-Free Adult Population

• Ninety-three percent of healthy subjects exhibit a meaningful conditioned pain modulation (CPM) effect.
• There is no gender difference in CPM effect.
• CPM effect does not appear to depend on the intensity of the conditioning stimulus, provided it is sufficiently noxious.

Conditioned pain modulation (CPM) encompasses 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 suggesting that inherent factors such as gender or genetics may be influential. However, there is no consensus on how best to determine a meaningful CPM effect. This study aimed to determine the proportion of pain-free subjects exhibiting a meaningful CPM effect. Analyses of associations between 5HTTLPR (serotonin transporter-linked polymorphic region) polymorphisms on the serotonin transporter gene (SLC6A4), gender, and CPM effect were also carried out. A total of 125 healthy subjects (47 male; 78 female) underwent pressure pain threshold 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 pressure pain threshold values from baseline greater than the inherent error of measurement, calculated as 5.3%. During the conditioning stimulus, 116 subjects (92.8%) exhibited a CPM effect whereas 9 did not. CPM effect did not differ 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 exhibit a meaningful CPM effect.PerspectiveThis 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 elucidate the mechanisms driving CPM inefficiency in chronic pain.