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Even fewer knowledge is available in its impact on glia\u2010mediated nociceptive sensitization. This study aims to elucidate the modulation of <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> on nerve injury\u2010induced pain development and activation of spinal mitogen\u2010activated protein kinases (<jats:styled-content style=\"fixed-case\">MAPKs<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a rat spinal nerve ligation (<jats:styled-content style=\"fixed-case\">SNL<\/jats:styled-content>) model, a low\u2010volt <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> treatment was applied to the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activations, including p\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p\u2010p38, as well as <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 level in the spinal dorsal horn were assessed and the cell types that expressed <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activation were identified by double immunofluorescence staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that <jats:styled-content style=\"fixed-case\">SNL<\/jats:styled-content> promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p\u2010p38 in the spinal dorsal horn. <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> significantly attenuated <jats:styled-content style=\"fixed-case\">SNL<\/jats:styled-content>\u2010induced mechanical allodynia and thermal hyperalgesia for 5\u20137 days. <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> also inhibited <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> significantly suppressed expression of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 in the spinal dorsal horn throughout the course.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low\u2010volt <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> significantly ameliorated <jats:styled-content style=\"fixed-case\">SNL<\/jats:styled-content>\u2010induced acute pain. Inferentially, <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> may inhibit spinal sensitization by down\u2010regulating spinal <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activations and activation\u2010mediated cytokine release. We demonstrated that early <jats:styled-content style=\"fixed-case\">PRF<\/jats:styled-content> treatment in acute nerve injury helps to ameliorate neuropathic pain development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2013.00419.x","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T10:28:33Z","timestamp":1383215313000},"page":"659-670","source":"Crossref","is-referenced-by-count":38,"title":["Pulsed radiofrequency inhibited activation of spinal mitogen\u2010activated protein kinases and ameliorated early neuropathic pain in rats"],"prefix":"10.1002","volume":"18","author":[{"given":"M.\u2010L.","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering National Taiwan University  Taipei Taiwan"},{"name":"Pain Center Zhongxing Branch of Taipei City Hospital  Taipei 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