Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain

J Pain. 2017 Jul;18(7):835-843. doi: 10.1016/j.jpain.2017.02.434. Epub 2017 Mar 7.


Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study 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. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results.

Perspective: This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials.

Keywords: Placebo analgesia; chronic pain; fibromyalgia; long-term pain; pain inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesia*
  • Chronic Pain / complications
  • Chronic Pain / physiopathology*
  • Female
  • Fibromyalgia / complications
  • Fibromyalgia / physiopathology*
  • Humans
  • Middle Aged
  • Pain Measurement
  • Pain Perception / physiology*
  • Placebo Effect*

Associated data

  • EudraCT/2004-004249-16