The direction and magnitude of conditioned pain modulation is dependent on test stimulus intensity in healthy participants but not in those with fibromyalgia

Abstract

Conditioned pain modulation (CPM) is a psychophysical phenomenon considered to be a measure of endogenous descending pain modulatory mechanisms. Previous rodent data from our lab demonstrated that test stimulus intensity affects CPM’s direction, with higher-intensity stimuli leading to hypoalgesia (i.e., CPM) and lower-intensity stimuli leading to hyperalgesia (i.e., “anti-CPM”). Our primary aim was to see if we could replicate these findings in humans. Because deficits in CPM suggest low capacity to inhibit pain—a risk factor for chronic pain—the secondary aim of this study was to see how this “anti-CPM” phenomenon presented itself in chronic pain patients with fibromyalgia. Healthy controls (n=51) and participants with fibromyalgia (n=39) underwent an individual heat pain threshold assessment, followed by a single CPM trial, at –1, +1, or +3 °C below/above their threshold. The CPM trial consisted of two baseline sub/suprathreshold heat pain stimulations (the test stimulus), a 30-s cold pressor test (4 °C) as a conditioning stimulus, and a final heat pain stimulation at the same temperature, with pain ratings provided throughout. Healthy controls displayed statistically significant CPM analgesia at +3 °C, no change at +1 °C, and hyperalgesia (anti-CPM) at −1 °C. Further analyses revealed that subjective intensity of the test stimulus determined the direction and magnitude of CPM. We observed no significant evidence for either analgesic CPM or anti-CPM in participants with fibromyalgia, suggesting that the mechanism(s) subserving both phenomena are dysfunctional in them.

Perspective

Similar to previous work in rodents, we show here that the use of lower-intensity test stimuli leads to hyperalgesic, instead of analgesic, conditioned pain modulation (CPM). Neither form of CPM was observed in participants with fibromyalgia.