Biopsychosocial influence on shoulder pain: results from a randomized preclinical trial of exercise-induced muscle injury

Pain. 2023 Feb 1;164(2):305-315. doi: 10.1097/j.pain.0000000000002700. Epub 2022 May 23.


Prior cohort studies validated that a subgroup defined by a specific COMT genotype and pain catastrophizing is at increased risk for heightened responses to exercise-induced or surgically induced shoulder pain. In this clinical trial, we used our preclinical model of exercise-induced muscle injury and pain to test the efficacy of interventions matched to characteristics of this high-risk subgroup (ie, personalized medicine approach). Potential participants provided informed consent to be screened for eligibility based on subgroup membership and then, as appropriate, were enrolled into the trial. Participants (n = 261) were randomized to 1 of 4 intervention groups comprised of pharmaceutical (propranolol or placebo) and informational (general education or psychologic intervention) combinations. After muscle injury was induced, participants received randomly assigned treatment and were followed for the primary outcome of shoulder pain intensity recovery over 4 consecutive days. Recovery rates were 56.4% (placebo and psychologic intervention), 55.4% (placebo and general education), 62.9% (propranolol and psychologic intervention), and 56.1% (propranolol and general education). No statistical differences were found between intervention groups in the primary analyses. Additional analyses found no differences between these intervention groups when shoulder pain duration was an outcome, and no differential treatment responses were detected based on sex, race, or level of pain catastrophizing. This trial indicates that these treatments were not efficacious for this high-risk subgroup when shoulder pain was induced by exercise-induced muscle injury. Accordingly, this phenotype should only be used for prognostic purposes until additional trials are completed in clinical populations.

Trial registration: NCT02620579.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Exercise Therapy / methods
  • Humans
  • Muscles
  • Propranolol*
  • Shoulder Pain* / etiology
  • Shoulder Pain* / psychology
  • Shoulder Pain* / therapy


  • Propranolol

Associated data