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To explore this, 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). Methods: Ten participants with a diagnosis of chronic widespread muscle pain (CWMP) were matched by age and reported gender to ten participants without muscle pain (i.e., no pain (NP)). Participants completed a standardized DOMS protocol. Pain intensity in the arm at rest and with movement was assessed using daily electronic diaries. Peak pain, the timing of peak pain, and the time to recovery were compared between groups. Associations of pain variables with the functional connectivity of the sensorimotor (SMN), cerebellum, frontoparietal control (FPN), and default mode network (DMN) both within network nodes and the rest of the brain was assessed. Results: Significant differences in peak pain, the time to peak pain, and the time to recovery were noted between groups for both pain at rest and pain with movement after controlling for catastrophizing and pain resilience. Connectivity across the SMN, FPN, and DMN was associated with all pain-related variables. Significant group differences were identified between groups. Conclusions: A standardized muscle \u201cinjury\u201d protocol resulted in more pain, a longer time to peak pain, and a longer time to resolve pain in the patient group compared to the NP group. These differences were associated with differences in connectivity across brain regions related to sensorimotor integration and appraisal. These findings provide preliminary evidence of the dysregulation of responses to muscle (micro)trauma in people with chronic pain.<\/jats:p>","DOI":"10.3390\/brainsci14111102","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:11:24Z","timestamp":1730279484000},"page":"1102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Delayed Recovery After Exercise-Induced Pain in People with Chronic Widespread Muscle Pain Related to Cortical Connectivity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2832-6913","authenticated-orcid":false,"given":"Mark D.","family":"Bishop","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meryl J.","family":"Alappattu","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8564-7493","authenticated-orcid":false,"given":"Priyanka","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of El Paso, El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Staud","sequence":"additional","affiliation":[{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Rheumatology, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-6491","authenticated-orcid":false,"given":"Jeff","family":"Boissoneault","sequence":"additional","affiliation":[{"name":"Minnesota Alcohol and Pain Lab, Department of Anesthesiology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby","family":"Blaes","sequence":"additional","affiliation":[{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9353-0446","authenticated-orcid":false,"given":"Yonah","family":"Joffe","sequence":"additional","affiliation":[{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Geneen, L.J., Moore, R.A., Clarke, C., Martin, D., Colvin, L.A., and Smith, B.H. 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Neurosci."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/11\/1102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:24:14Z","timestamp":1760113454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/11\/1102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["brainsci14111102"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14111102","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]}}}