Effects of ethosuximide, a T-type Ca(2+) channel blocker, on dorsal horn neuronal responses in rats.
Plasticity in transmission and modulatory systems are implicated in mechanisms of neuropathic pain. Studies demonstrate the importance of high voltage-activated Ca(2+) channels in pain transmission, but the role of low voltage-activated, T-type Ca(2+) channels in nociception has not been investigated. The Kim and Chung rodent model of neuropathy [Pain 50 (1992) 355] was used to induce mechanical and cold allodynia in the ipsilateral hindpaw. In vivo electrophysiological techniques were used to record the response of dorsal horn neurones to innocuous and noxious electrical and natural (mechanical and thermal) stimuli after spinal nerve ligation. Spinal ethosuximide (5-1055 microg) exerted dose-related inhibitions of both the electrically and low- and high-intensity mechanical and thermal evoked neuronal responses and its profile remained unaltered after neuropathy. Measures of spinal cord hyperexcitability were most susceptible to ethosuximide. This study, for the first time, indicates a possible role for low voltage-activated Ca(2+) channels in sensory transmission.
Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK. e.matthews@ucl.ac.uk
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D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005013:Ethosuximide / Q000494:pharmacology*; D006358:Hot Temperature; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries
D000927:Anticonvulsants; D020747:Calcium Channels, T-Type; D005013:Ethosuximide