title: Adenosine A1 receptors mediate the intracisternal injection of orexin-induced antinociceptive action against colonic distension in conscious rats.
abstract: We have recently demonstrated that orexin acts centrally through the brain orexin 1 receptors to induce an antinociceptive action against colonic distension in conscious rats. Adenosine signaling is capable of inducing an antinociceptive action against somatic pain; however, the association between changes in the adenosinergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the adenosinergic system may be involved in visceral nociception, and thus, adenosine signaling may mediate orexin-induced visceral antinociception. Visceral sensation was evaluated based on the colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Subcutaneous (0.04-0.2mg/rat) or intracisternal (0.8-4μg/rat) injection of N(6)-cyclopentyladenosine (CPA), an adenosine A1 receptor (A1R) agonist, increased the threshold volume of colonic distension-induced AWR in a dose-dependent manner, thereby suggesting that CPA acts centrally in the brain to induce an antinociceptive action against colonic distension. Pretreatment with theophylline, an adenosine antagonist, or 1,3-dipropyl-8-cyclopentylxanthine, an A1R antagonist, subcutaneously injected potently blocked the centrally injected CPA- or orexin-A-induced antinociceptive action against colonic distension. These results suggest that adenosinergic signaling via A1Rs in the brain induces visceral antinociception and that adenosinergic signaling is involved in the central orexin-induced antinociceptive action against colonic distension.
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: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003106:Colon / Q000294:innervation*; D003243:Consciousness; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008297:Male; D000068797:Orexins / Q000008:administration & dosage*; D010812:Physical Stimulation / Q000009:adverse effects; D058906:Purinergic P1 Receptor Agonists / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D059265:Visceral Pain / Q000188:drug therapy*; D014970:Xanthines
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics; D000068797:Orexins; D058906:Purinergic P1 Receptor Agonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine
keywords: Adenosine; Antinociception; Colonic distension; Orexin; Visceral sensation