PT - JOURNAL ARTICLE AU - Frangos, Eleni AU - Ceko, Marta AU - Wang, Binquan AU - Richards, Emily A. AU - Gracely, John L. AU - Colloca, Luana AU - Schweinhardt, Petra AU - Bushnell, M. Catherine TI - Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals AID - 10.1101/2020.07.31.231191 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.31.231191 4099 - http://biorxiv.org/content/early/2020/08/03/2020.07.31.231191.short 4100 - http://biorxiv.org/content/early/2020/08/03/2020.07.31.231191.full AB - Placebo analgesia is hypothesized to involve top-down engagement of prefrontal regions that access endogenous pain inhibiting opioid pathways. Fibromyalgia (FM) patients have neuroanatomical and neurochemical alterations in pathways relevant to placebo analgesia. Thus, it remains unclear whether placebo analgesic mechanisms would differ in FM patients compared to healthy controls (HCs). Here, using placebo-analgesia-inducing paradigms that included verbal suggestions and conditioning manipulations, we examined whether behavioral and neural placebo analgesic responses differed between 32 FM patients and 46 age- and sex-matched HCs. Participants underwent a manipulation scan, where noxious high and low heat were paired with the control and placebo cream, respectively, and a placebo experimental scan with equal noxious heat temperatures. Before the experimental scan, each participant received saline or naloxone, an opioid receptor antagonist. Across all participants, the placebo condition decreased pain intensity and unpleasantness ratings, decreased activity within the right insula and bilateral secondary somatosensory cortex, and modulated the Neurologic Pain Signature. There were no differences between HCs and FM patients in pain intensity ratings or neural responses during the placebo condition. Despite the perceptual and neural effects of the placebo manipulation, prefrontal circuitry was not activated during the expectation period and the placebo analgesia was unaltered by naloxone, suggesting placebo effects were driven more by conditioning than expectation. Together, these findings suggest that placebo analgesia can occur in both HCs and chronic pain FM patients, without the involvement of opiodergic prefrontal modulatory networks.Competing Interest StatementThe authors have declared no competing interest.