Facilitation of NMDA-induced currents and Ca2+ transients in the rat substantia gelatinosa neurons after ligation of L5-L6 spinal nerves.
This study employing a rodent model of neuropathic pain investigated the influence of partial nerve injury on the ability of NMDA receptor activation to induce membrane currents and rises in cytosolic concentration of free calcium ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole-cell patch-clamp recording and fura-2 calcium imaging in spinal slices. The novel findings are that: (I) L5-L6 spinal nerve ligation produces a sustained facilitation of NMDA-mediated membrane currents and [Ca2+]i rises both in the soma and dendrites of SG neurons on the injured side on post-operative days 4-13 after injury. (2) It appears that SG neurons in slices from injured rats recover from Ca2+ load less efficiently than neurons from naive rats. (3) The membrane depolarization-induced Ca2+ transients in SG neurons are not modified following spinal nerve ligation. The temporal profile of the changes in Ca2+ transients correlated well with the development of mechanical and thermal allodynia and hyperalgesia. These results suggest an important role of NMDA-mediated calcium signalling in the pathogenesis of neuropathic pain following spinal nerve injury.
Isaev
D
D
Department of Biomedical Sciences, Iowa State University, Ames 50011, USA.
Gerber
G
G
Park
S K
SK
Chung
J M
JM
Randik
M
M
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003714:Denervation / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008159:Lumbar Vertebrae; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013127:Spinal Nerves / Q000601:surgery; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate