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 st reptozotocin-induced diabetes. This is prevented by insulin and allevi ated by systemic lignocaine, but the aetiology is unknown. 2 Using ind welling lumbar intrathecal catheters to deliver pharmacological agents , we have investigated whether tactile allodynia in streptozotocin-dia betic rats is dependent on mechanisms associated with spinal sensitiza tion, by assessing the efficacy of agents that inhibit specific compon ents of spinal nociceptive processing. 3 Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium c hannel antagonist SNX 239, the alpha(2)-adrenoceptor agonist dexmedeto midine, the mu-opioid receptor agonist morphine, the N-methyl-D-aspart ate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonis t NBQX. 4 No effect on tactile allodynia was noted after intrathecal a dministration of the nitric oxide synthase inhibitor N-G-nitro-L-argin ine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, th e L-type calcium channel inhibitor diltiazem or any vehicle. 5 These d ata suggest that the tactile allodynia of diabetic rats involves spina l glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins.