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Without significant advances in our understanding of how acute pain becomes\nchronic, effective treatments will remain out of reach. This mini review will briefly summarize how\ncritical signaling pathways initiated during the early phases of peripheral nervous system inflammation\/\nneuroinflammation establish long-term modifications of sensory neuronal function. Together with\nthe recruitment of non-neuronal cellular elements, nociceptive transduction is transformed into a pathophysiologic\nstate sustaining chronic peripheral sensitization and pain. Inflammatory mediators, such\nas nerve growth factor (NGF), can lower activation thresholds of sensory neurons through posttranslational\nmodification of the pain-transducing ion channels transient-receptor potential TRPV1 and\nTRPA1. Performing a dual role, NGF also drives increased expression of TRPV1 in sensory neurons\nthrough the recruitment of transcription factor Sp4. More broadly, Sp4 appears to modulate a nociceptive\ntranscriptome including TRPA1 and other genes encoding components of pain transduction. Together,\nthese findings suggest a model where acute pain evoked by peripheral injury-induced inflammation\nbecomes persistent through repeated cycles of TRP channel modification, Sp4-dependent overexpression\nof TRP channels and ongoing production of inflammatory mediators.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1570159x21666230808111908","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T07:13:10Z","timestamp":1691651590000},"page":"6-14","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Peripheral Neuroinflammation and Pain: How Acute Pain Becomes\nChronic"],"prefix":"10.2174","volume":"22","author":[{"given":"Mark A.","family":"Schumacher","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Perioperative Care and the UCSF Pain and Addiction Research Center, University of\nCalifornia, San Francisco, California, 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","year":"2011","unstructured":"Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education2011","journal-title":"Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research"},{"key":"ref=2","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/S0140-6736(06)68700-X","volume":"367","author":"Kehlet H.","year":"2006","unstructured":"Kehlet H.; Jensen T.S.; Woolf C.J.; Persistent postsurgical pain: Risk factors and prevention. 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