Increased mRNA expression of the B1 and B2 bradykinin receptors and antinociceptive effects of their antagonists in an animal model of neuropathic pain.
We examined the role of B1 and B2 bradykinin receptors in promoting neuropathic hypersensitivity following peripheral nerve injury. Forty eight-hours following chronic constriction injury to a rat sciatic nerve there was an increased expression of B2 receptor mRNA in the lumbar dorsal root ganglia ipsilateral to the site of nerve injury. At 14 days following surgery there was also an ipsilateral increase of B1 receptor mRNA as well as a contralateral increased expression of B2 receptor mRNA. Increased expression of both receptors also coincided with analgesic effects of their antagonists. While HOE-140, a potent B2 receptor antagonist was analgesic at both time points tested, the B1 receptor antagonist des-Arg(9), [Leu(8)]-BK had an analgesic effect only at 14 days. The results support the concept that peripheral nerve injury is associated with local inflammation and that bradykinin, acting on both of its receptors promotes pain hypersensitivity.
Levy
Dan
D
Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Room 182A, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada.
Zochodne
Douglas W
DW
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003251:Constriction, Pathologic; D005727:Ganglia, Spinal / Q000378:metabolism; D006358:Hot Temperature; D008161:Lumbosacral Region; D008297:Male; D009422:Nervous System Diseases / Q000150:complications*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D001920:Bradykinin