Behavioral responses and Pre-emptive effect of MK-801 and morphine using SNI model in adult rat

Neuropathic pain syndromes are changes resulted from damage to nervous system. Since, treatments of neuropathic pain are poorly understood, existing treatments are often ineffective, and also experimental studies have documented that MK-801, a NMDA receptor antagonist, attenuates neuropathic pain, the purpose of this study was to investigate the behavioral responses and involvement of pre-emptive treatment of morphine and / or NMDA receptor antagonist MK-801, in Spared Nerve Injury (SNI) model of neuropathic pain. Experiments were performed on six groups (n=8) of male Sprague-Dawley rats (230-280g). Two animal groups were injected MK-801 (0.3 mg/kg, 20 min before, and 6 h after the operation) or morphine (8 mg/kg, 30 min prior to the operation). The third group was received both drugs with the same doses and protocols. Finally, the fourth group was received an equal volume of saline. Then, SNI procedure was performed by a ligation and axotomy of the tibial and common peroneal nerves and the sural nerve was left intact. The animals were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after performing SNI procedure of the sciatic nerve. Statistical analysis was performed using repeated measures ANOVA and the Tukey HSD test. Our data revealed that the SNI produces mechanical and cold allodynia and a hypersensitivity to noxious stimulations. Co-injection of morphine and MK-801 markedly declined cold allodynia at the day 14 (P<0.05) when compared with the saline group. The results of present study demonstrate that SNI model importantly influences the behavioral responses to both thermal and mechanical stimulations. It seems that co-administration of both drugs attenuates neuropathic pain in rat.