Mechanisms of the placebo response in pain in osteoarthritis

Osteoarthritis Cartilage. 2013 Sep;21(9):1229-35. doi: 10.1016/j.joca.2013.04.018.


Introduction: Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants.

Methods: A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review.

Results: Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs.

Conclusion: Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy.

Keywords: Endogenous opioids; Osteoarthritis; Placebo response.

Publication types

  • Review

MeSH terms

  • Arthralgia / therapy*
  • Brain / physiology*
  • Chronic Pain / therapy*
  • Humans
  • Osteoarthritis / therapy*
  • Placebo Effect*