Plasticity in spinal nociception after peripheral nerve section: reduced effectiveness of the NMDA receptor antagonist MK-801 in blocking wind-up and central sensitization of the flexor reflex

Abstract

We have examined and compared the effects of systemically applied MK-801, an NMDA receptor/channel blocker, on the wind-up and facilitation of the flexor reflex during and after conditioning stimulation (CS) of C-afferents in rats with intact sciatic nerves or 13–16 days after axotomy. In rats with intact sciatic nerves, intravenous MK-801 (0.5 mg/kg) partially reduced wind-up and totally blocked reflex facilitation following C-fiber CS to the sural nerve. In contrast, 13–16 days after unilateral section of the sciatic nerve, the same dose of MK-801 failed to reduce the wind-up and reflex facilitation following C-fiber CS to the axotomized sural nerve, although the duration of reflex facilitation was significantly shortened. These findings indicate that the involvement of NMDA receptors in mediating activity-dependent spinal hyperexcitability is substantially reduced after peripheral nerve section, possibly reflecting a reduced release of glutamate by primary sensory afferents.