NR2B receptors are involved in the mediation of spinal segmental reflex potentials but not in the cumulative motoneuronal depolarization in vitro.
Windup, the frequency dependent build-up of spinal neuronal responses is an electrophysiological model of the development of the central sensitization in the chronic pain states. NR2B subunit containing NMDA-type glutamate receptors are implicated in the windup of dorsal horn neurons, while their role at the motoneuronal level is controversial. The cumulative motoneuronal depolarization in hemisected rat spinal cord preparation is an in vitro model of windup. The role of NR2B receptors in this process, and in the mediation of dorsal root stimulation evoked ventral root reflex potentials was elucidated. Three selective NR2B antagonists; CP-101,606; CI-1041 and Co-101244 (1 microM) were used. They had only weak, but statistically significant inhibitory effect on the early part of ventral root response, and did not influence the cumulative depolarization. On the contrary, non-selective NMDA antagonist APV (40 microM) decreased both responses markedly. We conclude that the pharmacological sensitivities of windup at the sensory and motor levels are different. NR2B containing NMDA receptors have major role in the mediation of the windup of dorsal horn neurons, but their contribution to this phenomenon at the motor level is negligible.
Kocsis
Pál
P
Pharmacological and Drug Safety Research, Gedeon Richter Ltd., POB 27, H-1475 Budapest 10, Hungary. p.kocsis@richter.hu
Kovács
Gyula
G
Farkas
Sándor
S
Horváth
Csilla
C
Szombathelyi
Zsolt
Z
Tarnawa
István
I
D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000528:radiation effects; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine