title: L-type calcium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity.
abstract: In the dorsal horn of the spinal cord, pain-transmitting neurons exhibit action potential windup, a form of short-term plasticity, which consists of a progressive increase in neuronal response during repetitive stimulation of nociceptive input fibers. Windup depends on N-methyl-D-aspartate (NMDA) receptor activation, but previous in vitro studies indicated that windup also relies on intrinsic plateau properties of spinal neurons. In the present study, we considered the possible involvement of these properties in windup in vivo. For this purpose, we first studied a nociceptive flexion reflex in the rat. We showed that windup of the reflex is actually suppressed by blockers of L-type calcium current and Ca(2+)-activated non-specific cationic current (Ican), the two main depolarizing conductances of plateau potentials. We further showed that, during windup, NMDA receptors provide a critical excitatory component in a dynamic balance of excitatory and inhibitory inputs which ultimately activates L-type calcium channels. The nociceptive reflex involves at least two neuronal groups, which may express intrinsic amplification properties, motor neurons and dorsal horn neurons. By means of extracellular recordings in the dorsal horn, we showed that windup of dorsal horn neuron discharge was sensitive to the modulators of L-type calcium current. Altogether, our results suggest that, in vivo, windup also depends on the amplification properties of spinal neurons, the triggering of which requires previous activation of NMDA receptors.
authors.affiliation: INSERM E 358, Physiopathologie des Réseaux Neuronaux Médullaires, Université Bordeaux 2, Institut François Magendie, 33077 Bordeaux cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Fossat
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Gwendal
authors.initials: G
authors.lastname: Le Masson
authors.forename: Marc
authors.initials: M
authors.lastname: Landry
authors.forename: Frédéric
authors.initials: F
authors.lastname: Nagy
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000528:radiation effects; D013116:Spinal Cord / Q000166:cytology; D013331:Strychnine / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015763:2-Amino-5-phosphonovalerate; D013331:Strychnine