Adenosine A1 receptors mediate the intracisternal injection of orexin-induced antinociceptive action against colonic distension in conscious rats

• Published in: Journal of the neurological sciences 2016-03, Vol.362, p.106-110
• Main Authors: Okumura, Toshikatsu, Nozu, Tsukasa, Kumei, Shima, Takakusaki, Kaoru, Miyagishi, Saori, Ohhira, Masumi
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine A1 Receptor Antagonists - pharmacology; Analgesics - administration & dosage; Animals; Antinociception; Colon - innervation; Colonic distension; Consciousness; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Male; Neurology; Orexin; Orexins - administration & dosage; Physical Stimulation - adverse effects; Purinergic P1 Receptor Agonists - therapeutic use; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1 - metabolism; Reflex - drug effects; Visceral Pain - drug therapy; Visceral sensation; Xanthines
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2016.01.031

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 (0.04–0.2 mg/rat) or intracisternal (0.8–4 μg/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.