Biopsychosocial influence on shoulder pain: Rationale and protocol for a pre-clinical trial.
Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup.



Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation.



This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain.



ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015).
Duke Clinical Research Institute, Department of Orthopaedic Surgery, Duke University, Durham, NC 27715, USA. Electronic address: steven.george@duke.edu.
Steven Z
SZ
George
Department of Medicine, Univ. of Florida, Gainesville, FL 32610, USA. Electronic address: staudr@ufl.edu.
Roland
R
Staud
Applied Physiology and Kinesiology, Univ. of Florida, Gainesville, FL 32611, USA. Electronic address: pborsa@hhp.ufl.edu.
Paul A
PA
Borsa
Biostatistics, Univ. of Florida, Gainesville, FL 32610, USA. Electronic address: samwu@biostat.ufl.edu.
Samuel S
SS
Wu
Molecular Genetics and Microbiology, UF Genetics Institute, Univ. of Florida, Gainesville, FL 32610, USA. Electronic address: PhDpeggyw@mgm.ufl.edu.
Margaret R
MR
Wallace
Department of Physical Therapy, Univ. of Florida, Gainesville, FL 32610, USA. Electronic address: whgiii@phhp.ufl.edu.
Warren H
WH
Greenfield
School of Medicine, Saint Louis University, St. Louis, MO 63104, USA. Electronic address: mackieln@slu.edu.
Lauren N
LN
Mackie
Pain Research & Intervention Center of Excellence, Univ. of Florida, Gainesville, FL 32610, USA. Electronic address: rfillingim@dental.ufl.edu.
Roger B
RB
Fillingim
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D058443:Catastrophization / Q000235:genetics* / Q000523:psychology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D059350:Chronic Pain / Q000523:psychology / Q000628:therapy; D015444:Exercise / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010353:Patient Education as Topic / Q000458:organization & administration; D011433:Propranolol / Q000627:therapeutic use; D011613:Psychotherapy / Q000379:methods; D012107:Research Design; D012737:Sex Factors; D000070599:Shoulder Injuries / Q000150:complications; D020069:Shoulder Pain / Q000209:etiology / Q000523:psychology* / Q000628:therapy*; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D018836:Inflammation Mediators; D011433:Propranolol; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase