MK-801, and NMDA receptor antagonist, in the rostroventromedial medulla attenuates development of neuropathic symptoms in the rat

SEGMENTAL ligation of spinal nerves in the rat induces a long-lasting hyper algesia and allodynia that mimicks neuropathic conditions in humans. In the present study we attempted to determine whether supraspinal NMDA receptors contribute to the induction of the long-lasting hypersensitivity to noxiou s and innocuous mechanical stimulation following segmental ligation of spin al nerves in the rat. MK-801, an NMDA receptor antagonist, was microinjecte d into the rostroventromedial medulla,(RVM) 15 min before or 25 min after t he ligation of:spinal nerves and mechanical hypersensitivity was assessed a t various time points following surgery by determining the hindlimb withdra wal threshold to noxious,and innocuous mechanical stimulation. A single dos e of MK-801 administered prior to nerve ligation into the RVM significantly attenuated the development of mechanical hypersensitivity throughout the 2 week postoperative observation period, whereas corresponding administratio n of MK-801 immediately after-the nerve ligation attenuated the development of mechanical hypersensitivity only during the first postoperative day but not later. The results indicate that NMDA receptors in the RVM are involve d in triggering the enhanced sensitivity to mechanical stimulation induced: by a nerve injury. (C) 1999 Lippincott Williams & Wilkins.