The potentiative effect of ketamine on morphine-induced analgesia may be mediated via hippocampal cholinergic nicotinic receptors in a rat neuropathic pain model

Neuropathic pain can be induced due to peripheral nerve injury, diabetes, and also infectious diseases. Considering that morphine as a strong painkiller makes tolerance and addiction, the decrease of its dose or its co-administration with the other drugs may be a good strategy in pain management. The aim of the present study was to investigate whether Ketamine as a non-competitive NMDA receptor antagonist could increase the effect of the lower doses of morphine to induce the maximum analgesia in a rat neuropathic pain model. Moreover, the role of dorsal hippocampal nicotinic receptors was evaluated to show pain memory may have an important role in the encoding of pain information. The chronic constriction injury (CCI) surgery was simultaneously performed with hippocampal cannulation to induce neuropathic pain in Adult male Wistar rats (۲۰۰-۲۳۰ g). After ۱۴ days of recovery, the flexion withdrawal threshold for the mechanical stimuli was recorded before the surgery, before (baseline) and after the administrations of morphine, ketamine and/or mecamylamine using von Frey hairs. Two- and one-way ANOVA were used to analyze data for statistical significance (p < ۰.۰۵) through SPSS program. Systemic administration of morphine (۳-۵ mg/kg, i.p.) or ketamine (۰.۱-۰.۵ mg/kg, i.p.) increased the percentage of maximum possible effect (%MPE) to induce the neuropathic analgesia. Interestingly, ketamine potentiated the response of an ineffective dose of morphine to induce a strong analgesia. Intra-hippocampal microinjection of mecamylamine (۰.۵-۲ μg/rat), a cholinergic nicotinic receptor (nAchR) antagonist, also increased the effect of co-administration of morphine and ketamine in a rat neuropathic pain model. Thus, the potentiative effect of ketamine on the non-tolerant dose of morphine may be a good strategy in neuropathic pain therapy. Since the inactivation of hippocampal nicotinic receptors increased the ketamine/morphine-induced analgesia, it can be suggested that pain memory formation plays a critical role in neuropathic pain.

کلیدواژه ها:

Acute pain ، Opiate analgesia ، Mecamylamine ، rat(s)