Nocebo hyperalgesia in patients with fibromyalgia and healthy controls: An experimental investigation of conditioning and extinction processes at baseline and one-month follow-up - Preprint

Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in chronic pain patients compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of conditioned nocebo effects on pressure pain at baseline (N= 69) and one-month follow-up (N= 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions about the pain-increasing function of a sham TENS device, and then reduced via extinction. One month later, the same nocebo induction and reduction procedures were repeated to explore their stability. Our findings suggest an induction and reduction of nocebo effects in the healthy control group during baseline, with less clear evidence for these occurring in the patient group. During follow-up, nocebo effects were induced across both groups, but not reduced via extinction. 43% of all participants were nocebo responders in both sessions. Sensitivity analyses suggest that extinction was effective for nocebo responders in each session. Moreover, across all participants, the magnitudes of induced and reduced nocebo effects were stable between baseline and follow-up, without significant group effects over time. Our findings indicate that patients with fibromyalgia might be less responsive to the experimental manipulation of nocebo effects on pressure pain than healthy controls. Considering that nocebo responses are common in clinical settings, further investigation of conditioned nocebo effects is essential to minimize its role during treatment.