Nitric oxide mediates neuropathic pain behavior in peripherally denervated rats.
The involvement of spinal cord nitric oxide (NO) in the development of autotomy, a proposed behavioral model of denervation pain, was studied in sciatic and saphenous nerves transected rats injected intrathecally, 10-15 min prior to neurectomies, with NG-nitro-L-arginine methyl ester (L-NAME, 20-500 nmol), NG-nitro-D-arginine methyl ester (D-NAME, 500 nmol), L- or D-arginine (5 mumol), and 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP, 100 and 200 nmol). Self-inflicted lesions were scored daily for 8 weeks. The main effects on autotomy were: (1) a significant suppression in rats injected with L-NAME (500 nmol), but not with D-NAME; (2) a significant potentiation after L-arginine, but not D-arginine; and (3) a significant potentiation with 8-Br-cGMP, which was blocked by co-administration of L-NAME. These findings indicate that autotomy in rats can be modulated by blocking or enhancing nitroxidergic transmission at lumbosacral level, and suggest new therapeutic approaches for the prevention of certain pain syndromes, such as phantom limb pain.
Niedbala
B
B
Department of Pharmacology, Faculty of Medicine, University of La Laguna, Tenerife, Spain.
Sánchez
A
A
Feria
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D003714:Denervation; D004195:Disease Models, Animal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000502:physiology; D010591:Phantom Limb / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D019331:NG-Nitroarginine Methyl Ester