Effects of spinally administered P2X receptor agonists and antagonists on the responses of dorsal horn neurones recorded in normal, carrageenan-inflamed and neuropathic rats

1 The function and role of P2X receptors in the spinal transmission of noci ception was investigated using the selective P2X receptor agonists, alpha,b eta-methylene ATP (alpha,beta-me ATP) and beta,gamma-methylene-L-ATP (beta, gamma-me-L-ATP) and the P2X receptor antagonists pyridoxal-phosphate-6-azop henyl-2',4'-disulphonate (PPADS) and suramin. 2 Intrathecal administration of 5 and 50 mu g of beta,gamma-me-L-ATP produc ed a significant facilitation of the C-fibre evoked response and a tendency towards increased excitability of the post-dischargr, but not A beta-fibre evoked response of dorsal horn neurones recorded in normal animals. Admini stration of similar doses of cc,p-me ATP did not produce an overall change in the response of the neuronal population. 3 Peripheral administration of 20 mu g of these agonists into the paw of th e rat evoked firing in the dorsal horn neurones. 4 Intrathecal administration of the antagonists, suramin (50 and 500 mu g) and PPADS (5, 50 and 500 mu g), to normal animals and to animals with a mod el of neuropathy induced by spinal nerve ligation did not alter the evoked neuronal responses. In contrast, intrathecal administration of 500 mu g of suramin to animals 3 h after the induction of carrageenan inflammation prod uced a significant inhibition of the C-fibre evoked response of the neurone s. Similar inhibitions were also seen following high doses of intrathecal P PADS, although this did not reach significance. 5 These results suggest that spinal P2X receptors may play a role in the mo dulation of spinal nociceptive transmission following the development of in flammation, but that these receptors play at most a minor role in spinal no ciceptive processing in normal and neuropathic animals.