PRE-EMPTIVE EFFECTS OF MK-801 AND MORPHINE ON BEHAVIOURAL RESPONSES IN EXPERIMENTAL CHRONIC CONSTRICTION SCIATIC NERVE INJURY IN ADULT MALE RATS

Introduction: Neuropathic pain syndromes are changes resulting from damage to neuronal pathways that are characterized by spontaneous burning sensation with accompanying allodynia and hyperalgesia. Since the treatments of neuropathic pain are poorly understood and existing treatments are often ineffective, it is important to increase our understanding of the neuropathic pain states in order to identify strategies for the development of effective therapies. The purpose of this study was to investigate the involvement and pre-emptive treatment of morphine and / or NMDA receptor antagonist MK-801, and co-administration of both drugs on behavioural responses in an experimental model of neuropathic pain (CCI). Methods: Experiments were performed on six groups (n=8) of male Sprague-Dawley rats (230-280g). In the groups that received drugs, two groups were injected with 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). Another group received both drugs with the same doses and protocols. Finally, one group received normal saline in same volumes. The animals were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after CCI of the sciatic nerve. Results: Our data revealed that the CCI produces mechanical and cold allodynia and a hypersensitivity to noxious stimulations. MK-801 and morphine produced only a slight cold anti-allodynic response. On the other hand, co-injection of morphine and MK-801 markedly reduced cold allodynia at the days 7 (P<0.01), 14 (P<0.05) and 21 (P<0.05) when compared with the saline group. However, there was slight alleviation of the mechano allodynia, and, heat- and mechano-hyperalgesia. Results demonstrate that the CCI model importantly influences the behavioural responses to both the thermal and mechanical stimulations. Conclusion: We conclude that co-administration of both drugs can be more effective than MK-801 and morphine administered alone in the induced neuropathic pain.