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Biol Res. 2015 Jul 21;48:36. doi: 10.1186/s40659-015-0027-6.

Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique.

Author information

1
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. pinkpearl21.bluestar4@gmail.com.
2
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. arisaka@kdu.ac.jp.
3
Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan. obanesth-kitasato@memoad.jp.
4
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. shigekisakuraba@gmail.com.
5
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. takeo_sugita0827@yahoo.co.jp.
6
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. umezawa@kdu.ac.jp.
7
Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ami, Inashiki-gun, Ibaraki, 300-0394, Japan. kakuy@ipu.ac.jp.
8
Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. yoshida@kdu.ac.jp.
9
Faculty of Health Sciences, Uekusa Gakuen University, Ogura-cho, Wakaba-ku, Chiba, 264-0007, Japan. s-kuwana@uekusa.ac.jp.

Abstract

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 μM) or gabapentin (1 and 10 μM), but was increased by administration of 100 μM gabapentin. This evoked excitation was increased further in low Mg(2+) (0.8 mM) conditions, and this effect of low Mg(2+) concentration was antagonized by 30 μM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-aspartate (NMDA) receptor blocker. The increased excitation in low Mg(2+) 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 Mg(2+) 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 Mg(2+) 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.

PMID:
26195075
PMCID:
PMC4508818
DOI:
10.1186/s40659-015-0027-6
[Indexed for MEDLINE]
Free PMC Article

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