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

  • Landrew SevelEmail author
  • Jeff Boissoneault
  • Meryl Alappattu
  • Mark Bishop
  • Michael Robinson


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.


Endogenous pain modulation fMRI Delayed onset muscle soreness Pain imaging 



Research reported in this publication (REDCap access and support) was supported by the University of Florida Clinical and Translational Science Institute, which is supported in part by the NIH National Center for Advancing Translational Sciences under award number UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

The University of Florida Institutional Review Board approved the present study.

Informed consent

All participants provided written informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11682_2018_33_MOESM1_ESM.docx (767 kb)
ESM 1 (DOCX 766 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Landrew Sevel
    • 1
    Email author
  • Jeff Boissoneault
    • 2
  • Meryl Alappattu
    • 3
  • Mark Bishop
    • 3
  • Michael Robinson
    • 2
  1. 1.Osher Center for Integrative Medicine at Vanderbilt, Department of Physical Medicine & RehabilitationVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of Clinical and Health PsychologyUniversity of FloridaGainesvilleUSA
  3. 3.Department of Physical TherapyUniversity of FloridaGainesvilleUSA

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