MK-801, an 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 hyperalgesia 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 noxious and innocuous mechanical stimulation following segmental ligation of spinal nerves in the rat. MK-801, an NMDA receptor antagonist, was microinjected into the rostroventromedial medulla (RVM) 15 min before or 25 min after the ligation of spinal nerves and mechanical hypersensitivity was assessed at various time points following surgery by determining the hindlimb withdrawal threshold to noxious and innocuous mechanical stimulation. A single dose 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 administration 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 involved in triggering the enhanced sensitivity to mechanical stimulation induced by a nerve injury.

[1]  A. Pertovaara,et al.  Influence of preemptive treatment with MK-801, an N-methyl-D-aspartate receptor antagonist, on development of neuropathic symptoms induced by spinal nerve ligation in the rat. , 1999, Anesthesiology.

[2]  M. Urban,et al.  Involvement of excitatory amino acid receptors and nitric oxide in the rostral ventromedial medulla in modulating secondary hyperalgesia produced by mustard oil , 1999, Pain.

[3]  M. Urban,et al.  Role of glutamate receptors and nitric oxide in the rostral ventromedial medulla in visceral hyperalgesia , 1998, Pain.

[4]  A. Pertovaara,et al.  Influence of spinalization on spinal withdrawal reflex responses varies depending on the submodality of the test stimulus and the experimental pathophysiological condition in the rat , 1998, Brain Research.

[5]  A. Pertovaara.  A Neuronal Correlate of Secondary Hyperalgesia in the Rat Spinal Dorsal Horn Is Submodality Selective and Facilitated by Supraspinal Influence , 1998, Experimental Neurology.

[6]  A. Pertovaara,et al.  Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats , 1996, Neuroscience Letters.

[7]  G. Gebhart,et al.  Participation of central descending nociceptive facilitatory systems in secondary hyperalgesia produced by mustard oil , 1996, Brain Research.

[8]  G. Gebhart,et al.  Intracolonic zymosan produces visceral hyperalgesia in the rat that is mediated by spinal NMDA and non-NMDA receptors , 1996, Brain Research.

[9]  F. Cerveró,et al.  Supraspinal influences on the facilitation of rat nociceptive reflexes induced by carrageenan monoarthritis , 1996, Neuroscience Letters.

[10]  G. Bennett,et al.  Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat , 1993, Neuroscience Letters.

[11]  Jin Mo Chung,et al.  An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat , 1992, PAIN.

[12]  T. Yaksh,et al.  Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists , 1992, Pain.

[13]  H. Fields,et al.  Hyperalgesia during acute opioid abstinence: evidence for a nociceptive facilitating function of the rostral ventromedial medulla , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  Clifford J. Woolf,et al.  The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states , 1991, Pain.

[15]  A. Dickenson,et al.  Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following c fibre stimulation. , 1987, Neuropharmacology.