{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:32:28Z","timestamp":1783920748998,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Engineering Research Council of Canada (NSERC)","award":["RGPIN-2020-06777"],"award-info":[{"award-number":["RGPIN-2020-06777"]}]},{"name":"National Science and Engineering Research Council of Canada (NSERC)","award":["486901"],"award-info":[{"award-number":["486901"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["RGPIN-2020-06777"],"award-info":[{"award-number":["RGPIN-2020-06777"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["486901"],"award-info":[{"award-number":["486901"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Fibromyalgia syndrome (FM) is a chronic pain condition that affects a significant portion of the population; yet, this condition is still poorly understood. Prior research has suggested that individuals with FM display a heightened sensitivity to pain and signs of autonomic dysfunction. Recent advances in functional MRI analysis methods to model blood-oxygenation-level-dependent (BOLD) responses across networks of regions, and structural and physiological modeling (SAPM) have shown the potential to provide more detailed information about altered neural activity than was previously possible. Therefore, this study aimed to apply novel analysis methods to investigate altered neural processes underlying pain sensitivity in FM in functional magnetic resonance imaging (fMRI) data from the brainstem and spinal cord. Prior fMRI studies have shown evidence of functional differences in fibromyalgia (FM) within brain regions associated with pain\u2019s motivational aspects, as well as differences in neural activity related to pain regulation, arousal, and autonomic homeostatic regulation within the brainstem and spinal cord regions. We, therefore, hypothesized that nociceptive processing is altered in FM compared to healthy controls (HCs) in the brainstem and spinal cord areas linked to autonomic function and descending pain regulation, including the parabrachial nuclei (PBN) and nucleus tractus solitarius (NTS). We expected that new details of this altered neural signaling would be revealed with SAPM. The results provide new evidence of altered neural signaling in FM related to arousal and autonomic homeostatic regulation. This further advances our understanding of the altered neural processing that occurs in women with FM.<\/jats:p>","DOI":"10.3390\/brainsci14050450","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T09:50:07Z","timestamp":1714470607000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Investigating Descending Pain Regulation in Fibromyalgia and the Link to Altered Autonomic Regulation by Means of Functional MRI Data"],"prefix":"10.3390","volume":"14","author":[{"given":"Shima","family":"Hassanpour","sequence":"first","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannan","family":"Algitami","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8622-2414","authenticated-orcid":false,"given":"Maya","family":"Umraw","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Merletti","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4821-9611","authenticated-orcid":false,"given":"Brieana","family":"Keast","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9814-260X","authenticated-orcid":false,"given":"Patrick W.","family":"Stroman","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"},{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"},{"name":"Department of Physics, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.neuroimage.2007.12.016","article-title":"Investigation into the neural correlates of emotional augmentation of clinical pain","volume":"40","author":"Schweinhardt","year":"2008","journal-title":"Neuroimage"},{"key":"ref_2","first-page":"1065","article-title":"Fibromyalgia: One year in review 2022","volume":"40","author":"Giorgi","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1152\/jn.00276.2021","article-title":"Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: An fMRI study","volume":"126","author":"Staud","year":"2021","journal-title":"J. Neurophysiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12187","DOI":"10.1073\/pnas.0611404104","article-title":"Baseline brain activity fluctuations predict somatosensory perception in humans","volume":"104","author":"Boly","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/hbm.26228","article-title":"Proof-of-concept of a novel structural equation modelling approach for the analysis of functional magnetic resonance imaging data applied to investigate individual differences in human pain responses","volume":"44","author":"Stroman","year":"2023","journal-title":"Hum. Brain Mapp."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fneur.2016.00109","article-title":"Sympathetic Responses to Noxious Stimulation of Muscle and Skin","volume":"7","author":"Burton","year":"2016","journal-title":"Front. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"862976","DOI":"10.3389\/fneur.2022.862976","article-title":"Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain","volume":"13","author":"Ioachim","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Warren, H.J., Ioachim, G., Powers, J.M., Staud, R., Pukall, C., and Stroman, P.W. (2024). Using Structural Equation Modeling to Investigate the Neural Basis of Altered Pain Processing in Fibromyalgia with Functional Magnetic Resonance Imaging. Med. Res. Arch., 12.","DOI":"10.18103\/mra.v12i3.5206"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Stroman, P.W., Umraw, M., Keast, B., Algitami, H., Hassanpour, S., and Merletti, J. (2023). Structural and Physiological Modeling (SAPM) for the Analysis of Functional MRI Data Applied to a Study of Human Nociceptive Processing. Brain Sci., 13.","DOI":"10.3390\/brainsci13111568"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1171160","DOI":"10.3389\/fpain.2023.1171160","article-title":"Distinct neural signaling characteristics between fibromyalgia and provoked vestibulodynia revealed by means of functional magnetic resonance imaging in the brainstem and spinal cord","volume":"4","author":"Ioachim","year":"2023","journal-title":"Front. Pain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.semarthrit.2016.08.012","article-title":"2016 Revisions to the 2010\/2011 fibromyalgia diagnostic criteria","volume":"46","author":"Wolfe","year":"2016","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/art.1780330203","article-title":"The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee","volume":"33","author":"Wolfe","year":"1990","journal-title":"Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/acr.20140","article-title":"The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity","volume":"62","author":"Wolfe","year":"2010","journal-title":"Arthritis Care Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_15","unstructured":"Spielberger, C.D. (2010). Corsini Encyclopedia of Psychology, John Wiley & Sons, Inc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1037\/h0047358","article-title":"A new scale of social desirability independent of psychopathology","volume":"24","author":"Crowne","year":"1960","journal-title":"J. Consult. Psychol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1037\/1040-3590.7.4.524","article-title":"The Pain Catastrophizing Scale: Development and Validation","volume":"7","author":"Bishop","year":"1995","journal-title":"Psychol. Assess."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.mayocp.2012.10.013","article-title":"COMPASS 31: A refined and abbreviated Composite Autonomic Symptom Score","volume":"87","author":"Sletten","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R120","DOI":"10.1186\/ar2783","article-title":"The Revised Fibromyalgia Impact Questionnaire (FIQR): Validation and psychometric properties","volume":"11","author":"Bennett","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pain.2009.02.007","article-title":"Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2)","volume":"144","author":"Dworkin","year":"2009","journal-title":"Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1152\/jn.1997.78.2.992","article-title":"Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode","volume":"78","author":"Vierck","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Stroman, P.W., Bosma, R.L., Cotoi, A.I., Leung, R.H., Kornelsen, J., Lawrence-Dewar, J.M., Pukall, C.F., and Staud, R. (2016). Continuous Descending Modulation of the Spinal Cord Revealed by Functional MRI. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167317"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ioachim, G., Powers, J.M., Warren, H.J.M., and Stroman, P.W. (2020). Coordinated Human Brainstem and Spinal Cord Networks during the Expectation of Pain Have Elements Unique from Resting-State Effects. Brain Sci., 10.","DOI":"10.3390\/brainsci10090568"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1097\/j.pain.0000000000001302","article-title":"Pain processing in the human brainstem and spinal cord before, during, and after the application of noxious heat stimuli","volume":"159","author":"Stroman","year":"2018","journal-title":"Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.jpain.2007.06.006","article-title":"Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients","volume":"8","author":"Staud","year":"2007","journal-title":"J. Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0304-3959(00)00432-2","article-title":"Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome","volume":"91","author":"Staud","year":"2001","journal-title":"Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5038","DOI":"10.1002\/hbm.22993","article-title":"Neural correlates of temporal summation of second pain in the human brainstem and spinal cord","volume":"36","author":"Bosma","year":"2015","journal-title":"Hum. Brain Mapp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2147\/JPR.S290795","article-title":"How fMRI Analysis Using Structural Equation Modeling Techniques Can Improve Our Understanding of Pain Processing in Fibromyalgia","volume":"14","author":"Warren","year":"2021","journal-title":"J. Pain Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Powers, J.M., Ioachim, G., and Stroman, P.W. (2018). Ten Key Insights into the Use of Spinal Cord fMRI. Brain Sci., 8.","DOI":"10.3390\/brainsci8090173"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Stroman, P.W., Powers, J.M., Ioachim, G., Warren, H.J.M., and McNeil, K. (2021). Investigation of the neural basis of expectation-based analgesia in the human brainstem and spinal cord by means of functional magnetic resonance imaging. Neurobiol. Pain, 10.","DOI":"10.1016\/j.ynpai.2021.100068"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Stroman, P.W., Warren, H.J.M., Ioachim, G., Powers, J.M., and McNeil, K. (2020). A comparison of the effectiveness of functional MRI analysis methods for pain research: The new normal. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243723"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0301-0082(02)00009-6","article-title":"Descending control of pain","volume":"66","author":"Millan","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_33","unstructured":"Ilne, R.J., and West, A.R. (2001). Interactive effects of noradrenergic and serotonergic antidepressants on locus coeruleus neuronal activity. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fnint.2012.00094","article-title":"Modulation of physiological reflexes by pain: Role of the Locus Coeruleus","volume":"6","author":"Szabadi","year":"2012","journal-title":"Front. Integr. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157015908785777193","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part II: Physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans","volume":"6","author":"Samuels","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/01.psy.0000149258.42508.70","article-title":"The effect of sunlight on postoperative analgesic medication use: A prospective study of patients undergoing spinal surgery","volume":"67","author":"Walch","year":"2005","journal-title":"Psychosom. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0889-857X(01)00009-6","article-title":"Evaluation and management of endocrine dysfunction in fibromyalgia","volume":"28","author":"Geenen","year":"2002","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10827-022-00826-8","article-title":"Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey","volume":"50","author":"Demori","year":"2022","journal-title":"J. Comput. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/art.40746","article-title":"Altered Cervical Spinal Cord Resting-State Activity in Fibromyalgia","volume":"71","author":"Martucci","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Martinez-Lavin, M., Vidal, M., Barbosa, R.E., Pineda, C., Casanova, J.M., and Nava, A. (2002). Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830]. BMC Musculoskelet. Disord., 3.","DOI":"10.1186\/1471-2474-3-2"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1186\/ar1982","article-title":"Alteration of serotonin transporter density and activity in fibromyalgia","volume":"8","author":"Bazzichi","year":"2006","journal-title":"Arthritis Res. Ther."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/5\/450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:36:49Z","timestamp":1760107009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/5\/450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["brainsci14050450"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14050450","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]}}}