The induction of des-Arg9-bradykinin-mediated hyperalgesia in the rat by inflammatory stimuli.
1. The B1 receptor agonist des-Arg9-BK does not induce mechanical hyperalgesia when injected into the rat knee joint at 1-100 nmol, or thermal hyperalgesia when injected intravenously up to 1 mumol/kg. 2. Bradykinin (BK), administered into the joint, (1 nmol-1 mumol) induces a mechanical hyperalgesia, which is maximal by 4 h. Co-administration of BK with Hoe 140 (5 pmol) blocked development of the hyperalgesia, whereas des-Arg9-Leu8-BK (0.5 nmol) had no effect. Intravenous BK had no effect on thermal paw withdrawal latencies up to 1 mumol/kg. 3. Following joint inflammation induced by local Freund's complete adjuvant, intraarticular injection of des-Arg9-BK (0.05-10 nmol) and BK (0.5-100 nmol) caused a reduction in tolerated load. Co-administration of des-Arg9-Leu8-BK (0.5 nmol) with des-Arg9-BK (0.5 nmol) blocked development of the hyperalgesia, whereas Hoe 140 (5 pmol) had no effect. BK (1 nmol)-induced hyperalgesia was blocked by Hoe 140 but not des-Arg9-Leu8-BK. 4. Following UV irradiation of the paw, intravenous des-Arg9-BK and BK reduced paw withdrawal latencies to a noxious thermal stimulus indicating thermal hyperalgesia. The latency reduction induced by des-Arg9-BK and BK was prevented with co-administration of des-Arg9-Leu8-BK 200 nmol/kg, but not with Hoe 140 0.5 mumol/kg. 5. After interleukin-1 beta pre-treatment (1 unit into the joint or paw) des-Arg9-BK induced both thermal and mechanical hyperalgesia. Co-administration of des-Arg9-Leu8-BK 0.5 nmol with des-Arg9-BK 0.5 nmol into the joint prevented development of hyperalgesia and co-administration of des-Arg9-Leu8-BK (200 nmol/kg, iv) with des-Arg9-BK 10 nmol/kg prevented reduction of thermal withdrawal latencies. 6. These data suggest that after an inflammatory insult B1 receptors may play a role in the transduction of nociceptive information.
Davis
A J
AJ
Sandoz Institute for Medical Research, London, England.
Kelly
D
D
Perkins
M N
MN
D000818:Animals; D001168:Arthritis / Q000139:chemically induced; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time; D018002:Receptors, Bradykinin / Q000819:agonists / Q000187:drug effects; D014466:Ultraviolet Rays
D065168:Bradykinin Receptor Antagonists; D007375:Interleukin-1; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; D005620:Freund's Adjuvant; D001920:Bradykinin