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Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats
Author(s) -
Todorovic Slobodan M,
Rastogi A J,
JevtovicTodorovic Vesna
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705434
Subject(s) - nociception , ethosuximide , anticonvulsant , carbamazepine , gabapentin , pharmacology , neuropathic pain , analgesic , medicine , phenytoin , anesthesia , peripheral , receptor , epilepsy , pathology , alternative medicine , psychiatry
Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage‐ and ligand‐gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage‐gated Na + channel blockers, phenytoin and carbamazepine, and voltage‐gated Ca 2+ channel blockers, gabapentin and ethosuximide, induced dose‐dependent analgesia in the injected paw, with ED 50 values of 0.30, 0.32 and 8, 410 μ g per 100 μ l, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage‐gated Na + and Ca 2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage‐gated Na + and Ca 2+ channels may be useful analgesics.British Journal of Pharmacology (2003) 140 , 255–260. doi: 10.1038/sj.bjp.0705434

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