Spinal pharmacology of tactile allodynia in diabetic rats.
1. Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown. 2. Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing. 3. Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the alpha2-adrenoceptor agonist dexmedetomidine, the mu-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX. 4. No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle. 5. These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins.
Calcutt
N A
NA
Department of Pathology, University of California San Diego, La Jolla 92093-0612, USA.
Chaplan
S R
SR
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D020926:Medetomidine; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013311:Streptozocin
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013311:Streptozocin; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; D020926:Medetomidine