Lower placebo responses after long-term exposure to fibromyalgia pain

Abstract Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and since placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. Here we examined the placebo-group (n=37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. 22 patients were classified as placebo non-responders and 15 as responders, according to the Patient Global Impression of Change (PGIC) scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (VAS), FM impact (FIQ) and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity ( r =0.689, p =.004), but not among non-responders ( r =-0.348, p =.112). Here, we demonstrate that FM duration influences endogenous pain regulation, as pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, as endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. Clinical trial registration EudraCT 2004-004249-16. Perspective This article presents a novel perspective on placebo analgesia, as placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results demonstrate the importance of taking pain duration into account when interpreting the results from placebo-controlled trials.