{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:42:00Z","timestamp":1793029320465,"version":"4.5.0"},"reference-count":74,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001810","name":"Paralyzed Veterans of America Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VA Career Development Award","award":["1-IK2-RX-001123-01-A2"],"award-info":[{"award-number":["1-IK2-RX-001123-01-A2"]}]},{"name":"Taylor Foundation for Chronic Diseases"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Painful burn injuries are among the most debilitating form of trauma, globally ranking in the top 15 leading causes of chronic disease burden. Despite its prevalence, however, chronic pain after burn injury is under-studied. We previously demonstrated the contribution of the Rac1-signaling pathway in several models of neuropathic pain, including burn injury. However, Rac1 belongs to a class of GTPases with low therapeutic utility due to their complex intracellular dynamics. To further understand the mechanistic underpinnings of burn-induced neuropathic pain, we performed a longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury. Substantial evidence has identified Pak1 as promising a clinical target in cognitive dysfunction and is required for dendritic spine dysgenesis associated with many neurological diseases. In our burn injury model, mice exhibited significant tactile allodynia and heat hyperalgesia and dendritic spine dysgenesis in the dorsal horn. Activity-dependent expression of c-fos also increased in dorsal horn neurons, an indicator of elevated central nociceptive activity. To inhibit Pak1, we repurposed an FDA-approved inhibitor, romidepsin. Treatment with romidepsin decreased dendritic spine dysgenesis, reduced c-fos expression, and rescued pain thresholds. Drug discontinuation resulted in a relapse of cellular correlates of pain and in lower pain thresholds in behavioral tests. Taken together, our findings identify Pak1 signaling as a potential molecular target for therapeutic intervention in traumatic burn-induced neuropathic pain.<\/jats:p>","DOI":"10.1177\/1744806918788648","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T06:27:55Z","timestamp":1530253675000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury"],"prefix":"10.1177","volume":"14","author":[{"given":"Yiqun","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, 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