title: Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. pinkpearl21.bluestar4@gmail.com.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. arisaka@kdu.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Arisaka
authors.affiliation: Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan. obanesth-kitasato@memoad.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hosokawa
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. shigekisakuraba@gmail.com.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sakuraba
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. takeo_sugita0827@yahoo.co.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Sugita
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. umezawa@kdu.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Umezawa
authors.affiliation: Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ami, Inashiki-gun, Ibaraki, 300-0394, Japan. kakuy@ipu.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kaku
authors.affiliation: Division of Anesthesiology, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, 238-8580, Japan. yoshida@kdu.ac.jp.
authors.forename: Kazu-ichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Faculty of Health Sciences, Uekusa Gakuen University, Ogura-cho, Wakaba-ku, Chiba, 264-0007, Japan. s-kuwana@uekusa.ac.jp.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Kuwana
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D000077206:Gabapentin; D051381:Rats; D017208:Rats, Wistar; D014277:Trigeminal Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects* / Q000503:physiopathology; D056969:Voltage-Sensitive Dye Imaging; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin