Background & Aims

Exercise is a common intervention used in the management of many pain conditions including chronic musculoskeletal pain [1,2]. Muscle soreness and pain that develops after novel exercise is expected to peak at 48hrs and resolve over the next 72 to 96 hours [3, 4]. However, there is a subset of patients who become and stay in worse muscle pain after exercise [2]. We examined the responses of people with chronic primary pain to a standardized high intensity exercise protocol used to induce delayed onset muscle soreness (DOMS). We expected people with chronic primary muscle pain to have elevated and prolonged responses to exercise and explored how functional connectivity (FC) among cortical regions was associated with the time to peak pain and time to recovery.

Methods

10 people with chronic primary muscle pain (P) and 24 without pain (NP) participated. All were part of an ongoing clinical trial of exercise interventions. Participants completed a 9-minute resting state fMRI scan before completing a high intensity fatiguing isokinetic exercise protocol to induce arm pain. Pain intensity in the arm at rest and with movement was assessed with daily diaries collected for two weeks after pain induction using a 100mm visual analogue scale. Peak pain and time to peak were compared using t-tests. The times to peak pain and recovery (pain <5 out of 100) were tested using cox regression and Kaplan-Meier estimators. Association between time to peak pain and recovery and FC of the sensorimotor (SMN), cerebellar (CN), frontoparietal control, and default mode networks with the rest of the brain was assessed (PFDR<.05). For the SMN and CN, association of FC between nodes with the rest of the brain was compared between P and NP.

Results

Pain intensity in the arm at rest peaked at 16 for NP and 59 for P (p=0.002). This occurred 1 day after exercise for NP and 4.9 days for P (p=0.007). Cox regression results indicated a significant effect for group (p=0.01) based on pain at rest. Median time to recovery for 50% of NP was 2 days (d) and 11d for P. Pain with movement peaked at a median of 29 for NP and 65.5 for P (p=0.04). Median time to recovery occurred 1.7d after exercise for NP and 4d for P (p=0.07). Cox regression showed a significant effect for group (p=0.01). Median time to recovery for 50% of NP was 3d and 13d for P. FC of SMN with the right frontal operculum and greater CN FC with clusters inside the cerebellum was associated with shorter time to peak pain with movement. Greater FC of motor cortex with somatosensory cortex predicted shorter time to peak pain and recovery. Similarly, intracerebellar FC predicted time to peak pain with movement and recovery. In each case, P demonstrated lower FC than NP (p?.043).

Conclusions

People with chronic muscle pain had lower connectivity than pain-free controls in both the sensorimotor network and cerebellum, as well as, higher peak pain, longer time to peak pain, and longer time to resolve pain after a standardized muscle “injury” protocol. These findings provide preliminary evidence of CNS dysregulation of responses to muscle (micro)trauma in people with chronic pain.

References

1.Hody S, Croisier JL, Bury T, Rogister B, Leprince P. Eccentric Muscle Contractions: Risks and Benefits. Front Physiol. 2019 May 3;10:536. doi:10.3389/fphys.2019.00536. PMID: 31130877; PMCID: PMC6510035.

2.Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017 Jan 14;1(1):CD011279. doi:10.1002/14651858.CD011279.pub2. Update in: Cochrane Database Syst Rev. 2017 Apr 24;4:CD011279. PMID: 28087891; PMCID: PMC6469540.

3.Rice D, Nijs J, Kosek E, Wideman T, Hasenbring MI, Koltyn K, Graven-Nielsen T, Polli A. Exercise-Induced Hypoalgesia in Pain-Free and Chronic Pain Populations: State of the Art and Future Directions. J Pain. 2019 Nov;20(11):1249-1266. doi: 10.1016/j.jpain.2019.03.005. Epub 2019 Mar 21. PMID: 30904519.

4.Sevel L, Boissoneault J, Alappattu M, Bishop M, Robinson M. Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain. Brain Imaging Behav. 2020 Jun;14(3):881-896. doi: 10.1007/s11682-018-0033-8. PMID: 30617786.

Presenting Author

Mark D Bishop

Poster Authors

Mark Bishop

PhD

University of Florida

Lead Author

Meryl J Alappattu

DPT

Department of Physical Therapy, University of Florida

Lead Author

Priyanka Rana

MSPT

Department of Physical Therapy, University of Florida

Lead Author

Roland Staud

MD

Department of Rheumatology, University of Florida

Lead Author

Jeff Boissoneault

PhD

Department of Anesthesiology, University of Minnesota

Lead Author

Shelby Blaes

PhD

Department of Clinical and Health Psychology, University of Florida

Lead Author

Yonah Joffe

BS

Department of Clinical and Health Psychology, University of Florida

Lead Author

Micheal E Robinson

PhD

Department of Clinical and Health Psychology, University of Florida

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Muscle and Myofascial pain