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Biological Research

Print version ISSN 0716-9760

Abstract

MATSUMOTO, Akiko et al. Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique. Biol. Res. [online]. 2015, vol.48, pp.1-10. ISSN 0716-9760.  http://dx.doi.org/10.1186/S40659-015-0027-6.

BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in treating neuropathic pain and trigeminal neuralgia. In the present study, to analyze the effects of carbamazepine and gabapentin on neuronal excitation in the spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we recorded temporal changes in nociceptive afferent activity in the Sp5c of trigeminal nerve-attached brainstem slices of neonatal rats using a voltage-sensitive dye imaging technique. RESULTS: Electrical stimulation of the trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in the Sp5c. The optical signals were composed of two phases, a fast component with a sharp peak followed by a long-lasting component with a period of more than 500 ms. This evoked excitation was not influenced by administration of carbamazepine (10, 100 and 1,000 μΜ) or gabapentin (1 and 10 μΜ), but was increased by administration of 100 μΜ gabapentin. This evoked excitation was increased further in low Mg2+ (0.8 mM) conditions, and this effect of low Mg2+ concentration was antagonized by 30 μM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-as-partate (NMDA) receptor blocker. The increased excitation in low Mg2+ conditions was also antagonized by carbamazepine (1,000 μM) and gabapentin (100 μM). CONCLUSION: Carbamazepine and gabapentin did not decrease electrically evoked excitation in the Sp5c in control conditions. Further excitation in low Mg2+ conditions was antagonized by the NMDA receptor blocker AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation in the Sp5c in low Mg2+ conditions. Thus, we concluded that carbamazepine and gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to its anti-hypersensitivity in neuropathic pain.

Keywords : Carbamazepine; Gabapentin; Rat brainstem; Spinal trigeminal nucleus; Voltage-sensitive dye imaging.

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