The effect of combined systemic administration of morphine and L-name, a nitric oxide synthase inhibitor, on behavioral signs of neuropathic pain in rats

The controversy over using opioids for managing chronic neuropathic pain is widely acknowledged, and nitric oxide (NO) is suggested to play an important role in the maintenance of the behavioral signs of neuropathic pain. We evaluated the effect of combined systemic administration of morphine and N-G-nitro-L-arginine-methyl ester (L-NAME), a NO synthase (NOS) inhibitor, on allodynia in the spinal nerve ligation model of pain in rats. Nerve injury was produced by tight ligation of the left L5 and L6 spinal nerves and this procedure resulted in neuropathic pain behaviors in the ipsilateral hindlimb. Mechanical and cold allodynia were detected, respectively, by application of von Frey filaments or acetone to the plantar surface of the foot. Morphine (0.1-10 mg/kg, i.p.) and L-NAME (3-30 mg/kg, i.p.) reduced mechanical and cold allodynia with their higher doses. Combining subthreshold dose of L-NAME (3 mg/kg, i.p.) with morphine, an appreciable increase in the antiallodynic effect of morphine was observed. This effect was prevented by L-arginine (500 mg/kg, i.p.) and naloxone (I mg/kg, i.p.). These results suggest that combining morphine with a NOS inhibitor may be a promising approach in the treatment of neuropathic pain.