{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:38:11Z","timestamp":1793057891127,"version":"4.5.0"},"reference-count":29,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["21RX001359"],"award-info":[{"award-number":["21RX001359"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["21RX002366"],"award-info":[{"award-number":["21RX002366"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["CDA-2-034-07F"],"award-info":[{"award-number":["CDA-2-034-07F"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["CDA-2-065-10S"],"award-info":[{"award-number":["CDA-2-065-10S"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["CX000842-01A2"],"award-info":[{"award-number":["CX000842-01A2"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2-CX001508"],"award-info":[{"award-number":["IK2-CX001508"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-10-2-0169"],"award-info":[{"award-number":["W81XWH-10-2-0169"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Emerging evidence suggests mild traumatic brain injury related headache (MTBI-HA) is a form of neuropathic pain state. Previous supraspinal mechanistic studies indicate patients with MTBI-HA demonstrate a dissociative state with diminished levels of supraspinal prefrontal pain modulatory functions and enhanced supraspinal sensory response to pain in comparison to healthy controls. However, the relationship between supraspinal pain modulatory functional deficit and severity of MTBI-HA is largely unknown. Understanding this relationship may provide enhanced levels of insight about MTBI-HA and facilitate the development of treatments. This study assessed pain related supraspinal resting states among MTBI-HA patients with various headache intensity phenotypes with comparisons to controls via functional magnetic resonance imaging (fMRI). Resting state fMRI data was analyzed with self-organizing-group-independent-component-analysis in three MTBI-HA intensity groups (mild, moderate, and severe) and one control group (n\u2009=\u200916 per group) within a pre-defined supraspinal pain network based on prior studies. In the mild-headache group, significant increases in supraspinal function were observed in the right premotor cortex (T\u2009=\u20093.53, p\u2009&lt;\u20090.001) and the left premotor cortex (T\u2009=\u20093.99, p\u2009&lt;\u20090.0001) when compared to the control group. In the moderate-headache group, a significant (T\u2009=\u2009\u22123.05, p\u2009&lt;\u20090.01) decrease in resting state activity was observed in the left superior parietal cortex when compared to the mild-headache group. In the severe-headache group, significant decreases in resting state supraspinal activities in the right insula (T\u2009=\u2009\u22123.46, p\u2009&lt;\u20090.001), right premotor cortex (T\u2009=\u2009\u22123.30, p\u2009&lt;\u20090.01), left premotor cortex (T\u2009=\u2009\u22123.84, p\u2009&lt;\u20090.001), and left parietal cortex (T\u2009=\u2009\u22123.94, p\u2009&lt;\u20090.0001), and an increase in activity in the right secondary somatosensory cortex (T\u2009=\u20094.05, p\u2009&lt;\u20090.0001) were observed when compared to the moderate-headache group. The results of the study suggest that the increase in MTBI-HA severity may be associated with an imbalance in the supraspinal pain network with decline in supraspinal pain modulatory function and enhancement of sensory\/pain decoding.<\/jats:p>","DOI":"10.1177\/17448069211037881","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:26:56Z","timestamp":1628468816000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Severities in persistent mild traumatic brain injury related headache is associated with changes in supraspinal pain modulatory functions"],"prefix":"10.1177","volume":"17","author":[{"given":"Matthew","family":"Flowers","sequence":"first","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Leung","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"},{"name":"Department of Anesthesiology, The University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M","family":"Schiehser","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"},{"name":"Department of Psychiatry, The University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Metzger-Smith","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Delano-Wood","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"},{"name":"Department of Psychiatry, The University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Sorg","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"},{"name":"Department of Psychiatry, The University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6773-0863","authenticated-orcid":false,"given":"Alphonsa","family":"Kunnel","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeline","family":"Wong","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vaninetti","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"},{"name":"Department of Anesthesiology, The University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrokh","family":"Golshan","sequence":"additional","affiliation":[{"name":"Center for Pain and Headache Research, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"bibr1-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1179\/2042618613Y.0000000053"},{"key":"bibr2-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916662661"},{"key":"bibr3-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918810297"},{"key":"bibr4-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b8791a"},{"key":"bibr5-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004017"},{"key":"bibr6-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1037\/a0016906"},{"key":"bibr7-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2008.11.005"},{"key":"bibr8-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.12.014"},{"key":"bibr9-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4654-08.2009"},{"key":"bibr10-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e3282efc58b"},{"key":"bibr11-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.03.071"},{"key":"bibr12-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-18"},{"key":"bibr13-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2011.01623.x"},{"key":"bibr14-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1017\/S2045796019000088"},{"key":"bibr15-17448069211037881","first-page":"504","volume":"31","author":"Leung 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Fundamentals of data analysis methods in functional MRI. Advanced image processing in magnetic resonance imaging.  Boca Raton:  CRC Press, 2005, pp. 479\u2013501.","DOI":"10.1201\/9781420028669.pt5"},{"key":"bibr18-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20249"},{"key":"bibr19-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1109\/72.761722"},{"key":"bibr20-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-6080(00)00026-5"},{"key":"bibr21-17448069211037881","doi-asserted-by":"publisher","DOI":"10.1097\/01.HTR.0000271115.29954.27"},{"key":"bibr22-17448069211037881","doi-asserted-by":"crossref","unstructured":"Defrin R, Riabinin M, Feingold Y, Schreiber S, Pick CG. Deficient pain modulatory systems in patients with mild traumatic brain and chronic post-traumatic headache: implications on its mechanism.\n                      J Neurotrauma\n                      . Epub ahead of print 30 July 2014. 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