Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites.
Visceral pain is one of the most common forms of pain which is poorly understood. We now studied the influence of imidazoline/guanidinium compounds such as clonidine and guanfacine on visceral pain in the presence or absence of yohimbine and benazoline. To produce visceral pain-related behaviours, formalin (10%) was administered by inserting a fine cannula into the colon via the anus. Each experiment took 1 h. Clonidine (0.001, 0.01 and 0.1 mg/kg, i.p.) and guanfacine (2.5, 5 and 10 mg/kg, i.p.) produced analgesia dose dependently. The clonidine response was inhibited by yohimbine (0.2 mg/kg, i.p.). On the other hand, benazoline (5 mg/kg, i.p.) blocked the antinociceptive effect of guanfacine (5 mg/kg). Benazoline (2.5 and 5 mg/kg) itself also induced analgesia in inflammatory colonic pain. In this study, we used morphine to ensure that the behavioural responses were pain-related. Our results showed that morphine (2.5, 5 and 10 mg/kg, s.c.) produced a dose-dependent antinociception. The morphine (7 mg/kg, s.c.) response was reduced by naloxone (2 mg/kg, i.p.). However, we concluded that both imidazoline (I(2)) and alpha(2)-adrenoceptors may play a role in producing analgesia in visceral pain.
Sabetkasaie
Masoumeh
M
Department of Pharmacology and Neuroscience Research Center, School of Medicine, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran. fkasaei@yahoo.com
Vala
Setareh
S
Khansefid
Niaz
N
Hosseini
Ali-Reza
AR
Sadat Ladgevardi
Mohammad-Ali Raies
MA
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C487767:imidazoline receptor 2; D016316:Guanfacine; D003000:Clonidine