The role of nitric oxide in the development and maintenance of the hyperalgesia produced by intraplantar injection of carrageenan in the rat.
Activation of the N-methyl-D-aspartate (NMDA) receptor has been reported to be involved in the mechanisms that underlie thermal hyperalgesia produced by the intraplantar injection of carrageenan. As NMDA-mediated thermal hyperalgesia produced in models of acute and persistent pain have been reported to involve production of nitric oxide, we examined the role of nitric oxide in both the development and maintenance of the thermal hyperalgesia produced by the intraplantar injection of carrageenan. In addition, we examined the role of nitric oxide in the maintenance of the mechanical hyperalgesia produced by intraplantar injection of carrageenan. Prior to the intraplantar injection of carrageenan (2 mg in 100 microliters) there was no significant difference in thermal withdrawal latencies or mechanical withdrawal thresholds between the left and right hindpaws. Three hours after injection of carrageenan into the left hindpaw, rats showed evidence of a significantly faster thermal withdrawal latency and lower mechanical withdrawal threshold of the left hindpaw compared to the right hindpaw. In addition, the left hindpaw was significantly increased in size (diameter) compared with the right hindpaw. In these same rats, the intrathecal administration of saline, NG-nitro-L-arginine methyl ester (L-NAME; 2-200 nmol) or the inactive enantiomer, NG-nitro-D-arginine methyl ester (D-NAME; 200 nmol) did not produce any significant change in thermal nociceptive withdrawal latencies in the non-injected paw. However, administration of L-NAME (2-20 nmol), but not saline or D-NAME produced a dose dependent and reversible block of the thermal hyperalgesia for a period of up to 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Meller
S T
ST
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Cummings
C P
CP
Traub
R J
RJ
Gebhart
G F
GF
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002351:Carrageenan / Q000008:administration & dosage*; D004487:Edema / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D013997:Time Factors
D009569:Nitric Oxide; D002351:Carrageenan; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester