The long term analgesic effect of dipyrone was evaluated on a model of neuropathic pain and the role of nitric oxide/GMPc pathway in this antinociceptive mechanism. One intraplantar dipyrone administration (80 mg), at 14th day after the chronic constriction injury of the sciatic nerve, induced a significant and long term analgesic effect. The inhibition of nitric oxide synthase (NOS) with L-NAME (50 or 100 mg/paw) or scavenging of the endogenous NO with hemoglobin (10 or 30 mg/paw) inhibited the development of the dipyrone analgesia. L-arginine (500 mg/paw) could reverted the effect of L-NAME. Metylene blue (500 mg/paw) or ODQ (50 mg/paw) (blockers of guanyl cyclase), or glybenclamide (100, 200 or 300 mg/paw) (blocker of ATP-sensitive K+ channels) inhibited the development of dipyrone analgesia. The sodium nitroprussiate administered at 14th day after the chronic constriction injury of the sciatic nerve also induced a long term analgesic effect similar to that of dipyrone. Our data may support the suggestion that the peripheral and the long term analgesic action of dipyrone on this model experimental occurs due to a probable nociceptor desensitisation with involviment of activation of the nitric oxide-cGMP pathway, followed by an opening of ATP-sensitive K+ channels.
Neuropathic hyperalgesia; Chronic constriction injury; Dipyrone; Nitric oxide
