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

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.