Suppressive effects of oxcarbazepine on tooth pulp-evoked potentials recorded at the trigeminal spinal tract nucleus in cats.
1. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine, a keto derivitive of carbamazepine (an anticonvulsant), in an animal model. To evoke a nociceptive response, we electrically stimulated the maxillary canine tooth pulp (MCTP) in anaesthetized (allobarbital-urethane), spontaneously breathing cats. 2. The evoked potentials were recorded from the superficial layers of the caudal part of the trigeminal spinal tract nucleus (5ST). We examined a slow component with a large amplitude (the P3 component) in evoked compound potentials; its mean conduction velocity was 1.7 m/s, suggesting a response mediated by C-fibres. 3. To confirm that the P3 component was related to pain sensation, we used morphine, a most efficacious antinociceptive agent, in the present study. The P3 component was significantly suppressed by intravenous administration of morphine (3 mg/kg) and was also suppressed by microinjection of morphine (2 microg) into the recording site of the 5ST. These results suggest that the P3 component is involved in the transmission of nociceptive information. 4. We compared the effect of oxcarbazepine with mexiletine; both are known to block neuronal Na+ channels. Intravenous administration of mexiletine suppressed the P3 component at a dose of 5 mg/kg. Microinjection of mexiletine (10 microg) into the recording site of the 5ST tended to suppress the P3 component, but this effect was not significant. 5. Intravenous administration of oxcarbazepine (1-10 mg/kg) caused a dose-dependent inhibition of the P3 component, which was significantly suppressed at 10 mg/kg oxcarbazepine. Intravenous administration of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (MHD), a metabolite of oxcarbazepine, at doses of 3-30 mg/kg caused a dose-dependent inhibition of the P3 component. Oxcarbazepine was not available for the microinjection study because it is not water soluble. We used MHD for the microinjection study instead of oxcarbazepine, because MHD can be dissolved in water up to 3 mg/mL. Microinjections of MHD (6 microg) into the recording site of the 5ST suppressed the P3 component. These results indicate that oxcarbazepine has an antinociceptive action.
Kiguchi
S
S
Pharmacology Laboratory, Kissei Pharmaceutical Co. Ltd, Minamiazumi, Nagano, Japan. sumiyoshi_kiguchi@pharm.kissei.co.jp
Ichikawa
K
K
Kojima
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D002415:Cats; D003782:Dental Pulp / Q000187:drug effects / Q000502:physiology*; D003984:Dibenzazepines / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D000078330:Oxcarbazepine; D011092:Polyethylene Glycols / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000502:physiology*
D000701:Analgesics, Opioid; D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D003984:Dibenzazepines; D008801:Mexiletine; D002220:Carbamazepine; D011092:Polyethylene Glycols; D009020:Morphine; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide