{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:08:27Z","timestamp":1790161707066,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"the Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["22791457"],"award-info":[{"award-number":["22791457"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n The locus coeruleus (\n LC<\/jats:styled-content>\n ) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line\u2010derived neurotrophic factor (\n GDNF<\/jats:styled-content>\n ), a well\u2010established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether\n GDNF<\/jats:styled-content>\n is involved in pain modulation in the\n LC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Rats with chronic constriction injury (\n CCI<\/jats:styled-content>\n ) of the left sciatic nerve were used as a model of neuropathic pain.\n GDNF<\/jats:styled-content>\n was injected into the left\n LC<\/jats:styled-content>\n of rats with\n CCI<\/jats:styled-content>\n for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The \u03b1\n 2<\/jats:sub>\n \u2010adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in\n GDNF<\/jats:styled-content>\n \u2010mediated analgesia. The\n MEK<\/jats:styled-content>\n inhibitor\n U<\/jats:styled-content>\n 0126 was used to investigate whether the\n ERK<\/jats:styled-content>\n signalling pathway plays a role in the analgesic effects of\n GDNF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Both mechanical allodynia and thermal hyperalgesia were attenuated 24\u2009h after the first\n GDNF<\/jats:styled-content>\n injection.\n GDNF<\/jats:styled-content>\n increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of\n GDNF<\/jats:styled-content>\n . The analgesic effects of\n GDNF<\/jats:styled-content>\n were partly, but significantly, inhibited by prior injection of\n U<\/jats:styled-content>\n 0126 into the\n LC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n GDNF<\/jats:styled-content>\n injection into the\n LC<\/jats:styled-content>\n exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.13073","type":"journal-article","created":{"date-parts":[[2015,1,9]],"date-time":"2015-01-09T06:47:12Z","timestamp":1420786032000},"page":"2469-2478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Glial cell line\u2010derived neurotrophic factor\u2010mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic 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