Comparison of the visceral antinociceptive effects of spinally administered MPV-2426 (fadolmidine) and clonidine in the rat.
BACKGROUND
The authors determined the visceral antinociceptive effect induced by MPV-2426 (fadolmidine), a selective alpha 2 -adrenoceptor agonist, in rats with and without inflammation of the colon. They also determined whether the sympathetic nervous system or intact descending pathways are critical for the alpha 2 -adrenoceptor-induced visceral antinociception.


METHODS
Spinal neuronal responses evoked by colorectal distension were recorded in pentobarbitone-anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was used as a reference alpha 2 -adrenoceptor agonist. Inflammation of the colon was induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A midthoracic transection of the spinal cord was performed to study the role of descending pathways.


RESULTS
Spinal administration of MPV-2426 produced a dose-dependent attenuation of responses evoked by colorectal distension, and this effect was of the same percentual magnitude in inflamed as in noninflamed animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy but not influenced by spinal transection.


CONCLUSIONS
Spinally administered MPV-2426 produces a dose-dependent visceral antinociception as well in animals with an inflammation of the colon as in controls. The visceral antinociceptive effect induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact sympathetic nervous system or intact brainstem-spinal pathway is not critical for the MPV-2426-induced visceral antinociception.
Pertovaara
Antti
A
Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland. Antti.Pertovaara@utu.fi
Kalmari
Jaakko
J
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003092:Colitis / Q000503:physiopathology; D003106:Colon / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000008:administration & dosage; D012007:Rectum / Q000502:physiology; D013563:Sympathectomy, Chemical
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D007093:Imidazoles; D007189:Indans; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; C400294:radolmidine