Non-opioid actions of lamotrigine within the rat dorsal horn after inflammation and neuropathic nerve damage.
Some opioid-resistant pain conditions can be alleviated by voltage-dependent Na(+) channel blockers such as lamotrigine. The mu-opioid-receptor agonist morphine can modulate cation entry into cells to affect overall cellular excitability, an effect which can in turn be endogenously antagonised by the neuropeptide cholecystokinin (CCK). However, lamotrigine may also modulate cellular excitability by non-specifically blocking voltage-dependent ion channels. We have looked for interactions of lamotrigine with the opioid/CCK pathway within the spinal dorsal horn, to rule out the possibility that lamotrigine may attenuate nociceptive responses via actions on this pathway. Both lamotrigine and the mu-opioid agonist DAMGO inhibited mustard oil-evoked cell firing by approximately 50% compared with control levels. Co-application of CCK8S reversed DAMGO-, but not lamotrigine-induced inhibition of cell firing and this reversal was prevented with the selective CCK(B) receptor antagonist PD 135158. Although lamotrigine inhibited both brush- and cold-evoked cell firing in neuropathic animals, lamotrigine inhibition of mustard oil-evoked cell firing in the same animals was not significantly greater than that observed in controls. These results suggest that the antinociceptive properties of lamotrigine within the spinal dorsal horn are unlikely to be mediated via interactions with the opioid/CCK pathway.
Department of Preclinical Veterinary Sciences, The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Summerhall, Edinburgh, Summerhall, Edinburgh EH9 1QH, UK. gbm@neurosearch.dk
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Dickinson
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Fleetwood-Walker
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002766:Cholecystokinin / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D000077213:Lamotrigine; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009149:Mustard Plant; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*
D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D007211:Indoles; D018847:Opioid Peptides; D010936:Plant Extracts; D010938:Plant Oils; D014227:Triazines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C065600:PD 135158; D008536:Meglumine; D002766:Cholecystokinin; D012844:Sincalide; C027793:mustard oil; D000077213:Lamotrigine