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.
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.
Xu
X J
XJ
Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Zhang
X
X
Hökfelt
T
T
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D001369:Axons / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D009473:Neuronal Plasticity / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012026:Reflex, Stretch / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate