Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats.
We have recently demonstrated that orexin acts centrally in the brain to induce antinociceptive action against colonic distension through orexin 1 receptors in conscious rats. Although the dopaminergic system can induce antinociceptive action for somatic pain, the association between changes in the dopaminergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the dopaminergic system may be involved in visceral nociception, and if so, the dopaminergic system may mediate the orexin-induced visceral antinociception. Visceral sensation was evaluated using the colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Intracisternal injection of D1 (SKF38398) or D2 (quinpirole) dopamine receptor agonist increased the threshold volume of colonic distension-induced AWR in a dose-dependent manner. Pretreatment with either the D1 or D2 dopamine receptor antagonist (SCH23390 or sulpiride, respectively) potently blocked the centrally injected orexin-A-induced antinociceptive action against colonic distension. These results suggest for the first time that dopaminergic signaling via D1 and D2 dopamine receptors in the brain may induce visceral antinociception and that the dopaminergic signaling may be involved in the central orexin-induced antinociceptive action against colonic distension.
Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan. Electronic address: okumurat@asahikawa-med.ac.jp.
Toshikatsu
T
Okumura
Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Tsukasa
T
Nozu
Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Shima
S
Kumei
Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Kaoru
K
Takakusaki
Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Saori
S
Miyagishi
Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Masumi
M
Ohhira
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003108:Colonic Diseases / Q000378:metabolism / Q000503:physiopathology*; D004108:Dilatation, Pathologic; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D008297:Male; D000068797:Orexins / Q000378:metabolism / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D015398:Signal Transduction; D059265:Visceral Pain / Q000378:metabolism / Q000503:physiopathology*
D000700:Analgesics; D065127:Dopamine D2 Receptor Antagonists; D000068797:Orexins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine
Antinociception; Colonic distension; Dopamine; Orexin; Visceral sensation