Role of glutaminergic receptors in the rostral ventromedial medulla on antinociceptive effect of gabapentin in rat

Rostroventromedial medulla (RVM) is the most principal source of serotoninergic neurons to the dorsal horn of the spinal cord and it has important role in pain modulation. Rostroventromedial medulla neurons have glutaminergic receptors. Gabapentin is a novel anticonvulsant drug, which has antinociceptive used. Therefore, in the present study, we investigated the role of glutaminergic receptors in rostroventromedial medulla as an important supraspinal center, on antinociceptive effect of gabaoentin in rat.Methods and Materials: In this study, 56 NMRI male rats weighing 250-300 gr has been used. Surgical procedure and rostroventromedial medulla cannulation was done in stereotaxic apparatus for intranuclear injection of DNQX (1mg/ml saline) and/or MK-801 (6mg/ml saline) into this area as non-NMDA and NMDA antagonists, respectively. Animals were divided to 7 groups as Intact, Sham-operated, Gabepentin, DNQX, Gabapentin+ DNQX, MK-801 and Gabapentin+MK-801. Gabapentin was injected intraperitoneally (75mg/kg). Then tail-flick latency was recorded for 30 min in 5 min-intervals by tail flick analgesiometer. We used maximal possible effect of drug as an index for its analgesic effect. Gabapentin increases tail flick latency (5.86 ± 0.2 Sec) and maximal possible effect (32.64% ± 5.35) in compared to control group (3.81 ± 0.26 Sec). On the other hand, DNQX and/or MK-801 microinjection in combination with gabapentin, decreased tail flick latency (5.48 ± 0.36 and 4.85 ± 0.26 Sec, respectively) as compared to gabapentin group. These findings have been shown that a part of antinociceptive action of gabapentin is done through the rosroventromedial medulla. DNQX inhibits non-NMDA receptors in this area and activates its descending pathways to the dorsal horn of the spinal cord. Therefore, gabapentin can not be affected on the spinal cord and so, analgesic action of gabapentin is reduced. MK-801 inhibits NMDA receptors in rosroventromedial medulla and it also decreased analgesic effect of gabapentin. It’s possible that gabapentin enhances glutamate release and activates NMDA receptors in the rosroventromedial medulla.