{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:17:14Z","timestamp":1792649834676,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Pregabalin (PGB) is an \u03b1<jats:sub>2<\/jats:sub>\u03b4 calcium\u2010channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down\u2010regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked\u2010pain connectivity in humans receiving PGB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen female fibromyalgia patients participated in a randomized double\u2010blind 2\u2010period crossover study of PGB versus placebo. Before and after each period, patients underwent high\u2010resolution structural and evoked pressure\u2013pain functional brain imaging. GMV was analyzed using voxel\u2010based morphometry, and functional connectivity during evoked pressure\u2013pain was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Short\u2010term PGB treatment altered brain structure and evoked\u2010pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39600","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T15:14:24Z","timestamp":1453907664000},"page":"1511-1521","source":"Crossref","is-referenced-by-count":23,"title":["Association of Alterations in Gray Matter Volume With Reduced Evoked\u2010Pain Connectivity Following Short\u2010Term Administration of Pregabalin in Patients With Fibromyalgia"],"prefix":"10.1002","volume":"68","author":[{"given":"Tudor","family":"Puiu","sequence":"first","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anson E.","family":"Kairys","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, and University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Pauer","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development Groton Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schmidt\u2010Wilcke","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Ichesco","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson P.","family":"Hampson","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Napadow","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Clauw","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Harris","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3266"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2008.944"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1971"},{"key":"e_1_2_8_5_1","first-page":"CD007938","article-title":"Gabapentin for chronic neuropathic pain and fibromyalgia in adults","author":"Moore RA","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_6_1","first-page":"CD010782","article-title":"Anticonvulsants for fibromyalgia","author":"Uceyler N","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1756"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.06.019"},{"key":"e_1_2_8_9_1","unstructured":"Lyrica (pregabalin) prescribing information. 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