Interaction of NMDA and opioid receptors on thermal hyperalgesia and mechanical allodynia in two models of neuropathic pain



The use of multiple loose ligations of the rat sciatic nerve has been proposed as a model for the study of allodynia and hyperalgesia. This pain hypersensitivity results from both an increase in the peripheral and central sensitization. The evidence indicating that the development of neuropathic thermal hyperalgesia and mechanical allodynia requires activation of spinal cord NMDA receptors. NMDA antagonists are capable of blocking central sensitization associated with persistent noxious stimulation in experimental mononeuropathy and opioid tolerance. In addition, it has been reported that treatment with MK801 prevents the thermal hyperalgesia and mechanical allodynia. In the present study we attempted to find the interaction of NMAD receptor antagonist MK801 and opioid receptor agonist morphine in two nerve injury models of neuropathic pain in attenuation of hyperalgesia and allodynia. The experiments were carried out on male Sprauge-Dawley rats weighing 200-250 g. Under anesthesia, the sciatic nerve were exposed unilaterally and ligated loosely with 4-0 chromic gut. In SNI procedure axotomy and ligation of tibial and common peroneal nerves, leaving the sural nerve intact. We observed that pretreatment with NMDA recepor antagonist MK801 (0.3 mg/kg) does significantly attenuated thermal hyperalgesia and mechanical both SNI and CCI. Preemptive injection of morphine (8 mg/kg) had to a much lesser than MK801 in hyperalgesia and allodynia in SNI and CCI models. Co- administration of morphine and MK801 could eliminate the hyperesthetic and allodynia state following sciatic nerve injury. In conclusion, the present study shows that the opioids alone could actually contribute to the development of neuronal plastic changes via interactions with NMDA receptors. Then morphine during the pre-operative period in rats failed to affect the development of post-operative hyperalgesia and allodynia.