{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:44:00Z","timestamp":1772160240710,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We have shown using isolated C\u2010fiber\u2010like neurons that chronic pain may reduce orexinergic neural activity and that the nucleus accumbens, a major terminal area of the mesolimbic dopaminergic system, contains OX\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptors, a subtype of orexin receptors that inhibits accumbal basal dopamine efflux. It has been suggested that stimulation of OX\n                    <jats:sub>2<\/jats:sub>\n                    receptors in the brain may suppress chronic pain. To investigate how chronic pain affects orexin receptor\u2010mediated changes in accumbal dopaminergic neural activity, we analyzed the effects of intra\u2010accumbal infusion of orexin receptor ligands on accumbal dopamine efflux in rats using in\u00a0vivo microdialysis. To experimentally induce two types of chronic pain, i.e., inflammatory and neuropathic pain, we performed, respectively, intra\u2010plantar injection of the proinflammatory compound carrageenan into the hind paws and sciatic nerve ligation. Decreased paw withdrawal threshold following carrageenan treatment or sciatic nerve ligation was inhibited by morphine. However, meloxicam, a nonsteroidal anti\u2010inflammatory drug, inhibited these changes in carrageenan\u2010treated rats but not in those with sciatic nerve ligation. Neither carrageenan injection nor sciatic nerve ligation altered basal accumbal dopamine efflux. Both in carrageenan\u2010treated and in sciatic nerve\u2010ligated rats, the OX\n                    <jats:sub>1<\/jats:sub>\n                    \u2010 and OX\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptor antagonist MK\u20104305 and OX\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptor antagonist EMPA\u2010induced increase in accumbal dopamine efflux was reduced, as compared to their respective controls. The OX\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptor agonist orexin\u2010B counteracted the EMPA\u2010induced increase in dopamine efflux both in carrageenan\u2010treated and in sciatic nerve\u2010ligated rats. These results suggest that inflammatory and neuropathic pain each lead to decreased stimulation of accumbal OX\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptors by their endogenous agonists, orexin\u2010A and\/or orexin\u2010B, thereby inhibiting dopamine efflux.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70192","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T01:19:41Z","timestamp":1752455981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced Accumbal Dopamine Efflux Via Orexin OX\n                    <sub>2<\/sub>\n                    Receptors in Chronic Pain Models"],"prefix":"10.1111","volume":"62","author":[{"given":"Hiroki","family":"Kawashima","sequence":"first","affiliation":[{"name":"Department of Pharmacology Nihon University School of Dentistry at Matsudo  Chiba 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