Open AccessNeural correlates of conditioned pain responses in fibromyalgia subjects indicate preferential formation of new pain associations rather than extinction of irrelevant ones
Author(s) -
Angelica Sandström,
Isabel Ellerbrock,
Jeanette Tour,
Diana Kadetoff,
Karin Jensen,
Eva Kosek
Publication year - 2020
Publication title -
pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.524
H-Index - 258
eISSN - 1872-6623
pISSN - 0304-3959
DOI - 10.1097/j.pain.0000000000001907
Subject(s) - fibromyalgia , anterior cingulate cortex , insula , functional magnetic resonance imaging , psychology , dorsolateral prefrontal cortex , thalamus , neuroscience , insular cortex , prefrontal cortex , cingulate cortex , audiology , medicine , central nervous system , psychiatry , cognition
Behavioral studies have demonstrated aberrant safety processing in fibromyalgia subjects (FMSs) and suggested that patients accumulate new potential pain-related threats more effectively than extinguishing no longer relevant ones. The aim of the current study was to investigate the neural correlates of conditioned pain responses and their relationship with emotional distress in FMS (n = 67) and healthy controls (HCs, n = 34). Using functional magnetic resonance imaging, we traced conditioned pain responses to an identical moderately painful pressure (P30) depending on whether it was following a green (P30green) or a red (P30red) cue. The cues were previously associated with individually calibrated painful pressure stimuli of low and high intensity, corresponding to visual analogue scale 10 and 50 mm, respectively. Fibromyalgia subjects displayed increased P30green ratings over time, while P30red ratings remained elevated. Healthy controls adapted all pain ratings to resemble moderate pain. Fibromyalgia subjects exhibited increased activation for [P30green>P30red] in M1/anterior insula, whereas HC showed increased S2/mid-insula response to [P30red>P30green]. High pain catastrophizing scale (PCS) ratings in fibromyalgia (FM) covaried with heightened brain activation for [P30green] × PCS in left dorsolateral prefrontal cortex and medial prefrontal cortex/orbitofrontal cortex; and [P30green>P30red] × PCS in dorsal anterior cingulate cortex/mid-cingulate cortex; superior temporal pole, extending to anterior insula; bilateral thalamus; and posterior insula. Psychophysiological interaction analysis for FM [P30green>P30red] × PCS revealed a dissociation in functional connectivity between thalamus and bilateral inferior parietal lobe. In alignment with behavioral data, FMS displayed a cerebral response suggesting preferential formation of new pain-related associations while simultaneously maintaining no longer relevant ones. The opposite was observed in HC. Increased responses to pain-related threats in FM may contribute to dysfunctional pain-protective behaviors and disability.