Electroacupuncture combined with MK-801 prolongs anti-hyperalgesia in rats with peripheral inflammation

Our previous study showed that electroacupuncture (EA), an adjuvant to conventional medicine, significantly attenuated hyperalgesia in a rat model of inflammatory pain. In the present study, we evaluated the potential additive and/or synergism of EA and a sub-effective dose of dizocilpine maleate (MK-801), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, on hyperalgesia in the same rat model of inflammatory pain. Hyperalgesia, manifesting as decreased paw withdrawal latency (PWL) to a noxious stimulus, was induced by injecting complete Freund's adjuvant (CFA) into the plantar surface of one hind paw of each rat. EA treatments were given at acupoint GB30 immediately after and 2 h after CFA. MK-801 at 0.001 mg/rat was given (i.t.) 10 min before each of the two EA treatments. PWL was measured prior to and 2.5 and 5 h post-CFA. Ten and 100 Hz EA significantly inhibited CFA-induced hind paw hyperalgesia. Both 10 and 100 Hz EA combined with the sub-effective dose of 0.001 mg/rat MK-801 showed prolonged anti-hyperalgesia with no side effects. These results demonstrate that EA combined with a sub-effective dose of this NMDA receptor antagonist enhances anti-hyperalgesia, and this combination may provide an effective strategy for pain management.