Antinociceptive effect of a new P(2Z)/P2X7 antagonist, oxidized ATP, in arthritic rats.
The neurotransmitter adenosine triphosphate (ATP) is released from sensory nerve endings during inflammation and acts at the level of P2X receptors. We used the irreversible inhibitor of P2z/P2X7 receptor, designated oxidized ATP (oATP), to test its possible antinociceptive activity in arthritic rats. We induced unilateral inflammation of the rat hind paw by local injection of Freund's complete adjuvant. Administration of the adjuvant resulted in a significant reduction of paw pressure threshold (PPT). Injection of oATP into inflamed paws significantly increased, in a dose-dependent manner, PPT values to levels comparable with or higher than those evaluated in control uninflamed paws. The data indicate that the P2z/P2X7 receptor system exerts a role in nociception and that oATP, by inhibiting such a receptor, reduces the nociceptive signal in the course of peripheral inflammation.
Dell'Antonio
Giacomo
G
Department of Pathology, IRCCS H.S. Raffaele, Via Olgettina 60, Milan, Italy.
Quattrini
Angelo
A
Dal Cin
Elena
E
Fulgenzi
Alessandro
A
Ferrero
Maria Elena
ME
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7
D000345:Affinity Labels; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate