The Effect of L-NAME on Morphine Antinociception in Formalin Test

Introduction: N- nitro-L-arginine methyl ester (L-NAME), one of the L-arginine analogs, has been specified as an inhibitor of nitric oxide synthase ( NOS).Nitric oxide synthase is an enzyme which leads to nitric oxide synthesis. Since nitric oxide has been known as a pain mediator, it can be said that L-NAME can decrease and relieve pain. In this research the effect of L-NAME on morphine antinociception and the interaction between these two drugs were studied by using formalin test in rat. Methods: Experiments were done on 70 male-wistar rats weighing 180-230gr. Rats were divided into seven groups (n =10) including: the control group, the saline group(sham), the experimental group receiving 2mg/kg of morphine, and the experimental groups receiving 15, 20, 40mg/kg L-NAME and morphine (2mg/Rat), and the group receiving 40 mg/kg of L-NAME. Injections were performed intraperitoneally fifteen minutes before starting formalin test. In sham group, an equal volume of normal saline was injected intraperitoneally. The minutes (0-5) and (16-60) were respectively considered as acute and chronic phases of pain in the formalin test. After observing animals’ behavioural responses and calculating pain scores, groups were compared. Results: According to the obtained results, L-NAME caused a significant nociception decrease in both phases of formalin test and this effect was dose dependent. Moreover groups that received the combination of morphine and L-NAME showed more nocieception, especially in chronic phase of formalin test, in comparison to the groups that received each in isolatin and control groups (P<0.05). Conclusion: According to the results, L-NAME and morphine act synergistically. In other words, L-NAME with nitric oxide inhibitor decreases intracell signal activities of cGMP and CAMP and consequently protein Kinase A (PKA) activity related to cAMP is decreased. This leads to an increase in the releasing of neurotransmitters related to PKA, and consequently morphine antinociceptive effect is amplified.