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Brain Imaging Behav. 2019 Jan 8. doi: 10.1007/s11682-018-0033-8. [Epub ahead of print]

Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain.

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Osher Center for Integrative Medicine at Vanderbilt, Department of Physical Medicine & Rehabilitation, Vanderbilt University Medical Center, Suite 380, 3401 West End Avenue, Nashville, TN, 37203, USA.
Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA.
Department of Physical Therapy, University of Florida, Gainesville, FL, USA.


Analgesic treatments that aim to eliminate pain display marginal success in relieving chronic pain and may increase pain vulnerability. Repeated exposure to pain may result in increased pain modulation via engagement of anti-nociceptive brain regions. It was hypothesized that repeated exposure to delayed onset muscle soreness (DOMS) would result in increased pain modulatory capacity (PMC) via functional neural adaptation. 23 healthy participants completed Baseline and Follow Up resting-state fMRI and quantitative sensory testing (QST) visits 40 days apart. Participants were randomized to two groups: A Repeated DOMS Group (RD Group) that received four, weekly DOMS inductions and a Control Group that received one baseline induction. Daily pain ratings were collected for seven days post-induction, as were quantitative sensory testing (QST) metrics at baseline and Follow Up. Regional functional connectivity (FC) was estimated among areas involved in pain modulation. Seed and network FC was estimated among areas involved in pain modulation and sensory processing. Changes in FC were compared between groups. The RD Group displayed significant reductions in post-DOMS pain ratings and significant changes in thermal QST measures. RD Group participants displayed greater adaptation in nucleus accumbens-medial prefrontal cortex (NAc-mPFC) FC and in sensorimotor network (SMN) connectivity with the dorsomedial, ventromedial, and rostromedial prefrontal cortices. Changes in SMN-PFC connectivity correlated with reductions in post-DOMS affective distress. Results suggest that repeated exposure to clinically-relevant pain results in adaptations among brain regions involved in pain modulation. Repeated exposure to clinically-relevant pain may serve as a mechanism to increase PMC via inhibition of emotional valuation of painful stimuli.


Delayed onset muscle soreness; Endogenous pain modulation; Pain imaging; fMRI


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