title: Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats.
abstract: Levodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms. Visceral sensation was evaluated by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Subcutaneously (80 mg/rat) or intracisternally (2.5 μg/rat) administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. Electronic address: okumurat@asahikawa-med.ac.jp.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nozu
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Shima
authors.initials: S
authors.lastname: Kumei
authors.affiliation: Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takakusaki
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Miyagishi
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Ohhira
mesh_terms: D000700:Analgesics; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003243:Consciousness / Q000502:physiology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D059265:Visceral Pain / Q000188:drug therapy*
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D000700:Analgesics; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D017448:Receptors, Dopamine D2; D007980:Levodopa; D013469:Sulpiride; D014508:Urea
keywords: Antinociception; Colonic distension; Dopamine; Levodopa; Orexin