Impact of Propranolol and Psychologically Informed Intervention on Pain Sensitivity: Secondary Analysis from the Biopsychosocial Influence on Shoulder Pain Preclinical Randomized Trial

Mark D Bishop; Corey B Simon; Yanan Huo; Margaret R Wallace; Paul A Borsa; Roger B Fillingim; Roland Staud; Samuel S Wu; Steven Z George

doi:10.2147/JPR.S500140

Impact of Propranolol and Psychologically Informed Intervention on Pain Sensitivity: Secondary Analysis from the Biopsychosocial Influence on Shoulder Pain Preclinical Randomized Trial

J Pain Res. 2025 Apr 5:18:1837-1850. doi: 10.2147/JPR.S500140. eCollection 2025.

Authors

Mark D Bishop^{1

2

3}, Corey B Simon^{4

5}, Yanan Huo⁶, Margaret R Wallace⁷, Paul A Borsa⁸, Roger B Fillingim^{2

9}, Roland Staud¹⁰, Samuel S Wu¹¹, Steven Z George^{4

5

12}

Affiliations

¹ Department of Physical Therapy, University of Florida, Gainesville, FL, USA.
² Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.
³ Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL, USA.
⁴ Department of Orthopaedic Surgery, Physical Therapy Division, Duke University, Durham, NC, USA.
⁵ Duke Clinical Research Institute, Duke University, Durham, NC, USA.
⁶ Gilead Sciences, Inc., Foster City, CA, USA.
⁷ Department of Molecular Genetics and Microbiology, UF Genetics Institute, University of Florida, Gainesville, FL, USA.
⁸ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.
⁹ Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA.
¹⁰ Department of Medicine, University of Florida, Gainesville, FL, USA.
¹¹ Department of Biostatistics, University of Florida, Gainesville, FL, USA.
¹² Departments of Orthopaedic Surgery and Population Health Sciences, Duke University, Durham, NC, USA.

Abstract

Purpose: Measures of pain sensitivity have potential relevance for patient care. We previously identified a subgroup of people at risk for ongoing pain characterized by genetic AND psychological factors. Here, we report planned secondary analyses examining the effect of personalized interventions on pain sensitivity outcomes.

Patients and methods: Two hundred and sixty-one healthy individuals with the COMT SNP rs6269 AA genotype and Pain Catastrophizing Scale scores of 5 or higher received exercise-induced muscle injury, followed by a randomly assigned treatment: (1) general education and placebo; (2) personalized psychological intervention and placebo; (3) general education and propranolol; or (4) personalized psychological intervention and propranolol. Pain sensitivity outcomes (pressure pain thresholds (PPT), suprathreshold heat rating, temporal summation, and conditioned pain modulation efficiency) were compared using a mixed effect model to examine difference among groups, adjusted for age, sex and race.

Results: No main effects for group assignment were noted (p > 0.05 for all), when considered as 4 groups or 2 collapsed groups (ie propranolol vs placebo or personalized psychologic vs general education). Interaction terms were then entered into our models in an exploratory fashion. For PPT outcomes interactions were noted for, sex and time, and race and time (p<0.015). For temporal summation outcomes, interactions were noted for sex and group and race and group (p < 0.015).

Conclusion: Results indicated no statistically reliable changes in pain sensitivity when considering matched vs unmatched treatment groups. Caution is needed in this interpretation given that the trial was not powered to specifically identify these differences. Exploratory analysis of interactions among ethnic/racial and gender identities by treatment, however, showed the potential for differential effects for specific pain sensitivity measures. Significant interactions across modalities suggest analysis of higher order interactions/intersectionality could be of great interest for testing efficacy of personalized interventions in future trials.

Keywords: exercise; genetics; muscle; shoulder.

Plain language summary

Purpose: In previous work, we identified a set of genetic and cognitive traits that were associated with persistent pain after exercise induced muscle pain.

Participants and methods: In this current study, we tested whether a combination of information focused on how you think about pain and a medication tailored to a genetic risk factor would help people without clinical pain conditions recovery faster from exercise-induced muscle pain than using general information and placebo medication.

Results: The study did not strongly support that interventions matched to higher risk of persistent pain made changes for all the people. What we did find is that individuals’ ethnic, racial and gender identities might be influencing sensitivity to specific measures of pain sensitivity.

Conclusions: Interactions among individuals’ identities might impact pain sensitivity. These findings could be used to generate hypotheses for and/or inform future studies of individualized medicine approaches for pain.

Publication types

Case Reports
Clinical Trial