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

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...

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Autores principales: Matsumoto,Akiko, Arisaka,Hirofumi, Hosokawa,Yuki, Sakuraba,Shigeki, Sugita,Takeo, Umezawa,Nobuo, Kaku,Yuki, Yoshida,Kazu-ichi, Kuwana,Shun-ichi
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2015
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100036
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spelling oai:scielo:S0716-976020150001000362016-02-16Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging techniqueMatsumoto,AkikoArisaka,HirofumiHosokawa,YukiSakuraba,ShigekiSugita,TakeoUmezawa,NobuoKaku,YukiYoshida,Kazu-ichiKuwana,Shun-ichi Carbamazepine Gabapentin Rat brainstem Spinal trigeminal nucleus Voltage-sensitive dye imaging 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100036en10.1186/S40659-015-0027-6
institution Scielo Chile
collection Scielo Chile
language English
topic Carbamazepine
Gabapentin
Rat brainstem
Spinal trigeminal nucleus
Voltage-sensitive dye imaging
spellingShingle Carbamazepine
Gabapentin
Rat brainstem
Spinal trigeminal nucleus
Voltage-sensitive dye imaging
Matsumoto,Akiko
Arisaka,Hirofumi
Hosokawa,Yuki
Sakuraba,Shigeki
Sugita,Takeo
Umezawa,Nobuo
Kaku,Yuki
Yoshida,Kazu-ichi
Kuwana,Shun-ichi
Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
description 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.
author Matsumoto,Akiko
Arisaka,Hirofumi
Hosokawa,Yuki
Sakuraba,Shigeki
Sugita,Takeo
Umezawa,Nobuo
Kaku,Yuki
Yoshida,Kazu-ichi
Kuwana,Shun-ichi
author_facet Matsumoto,Akiko
Arisaka,Hirofumi
Hosokawa,Yuki
Sakuraba,Shigeki
Sugita,Takeo
Umezawa,Nobuo
Kaku,Yuki
Yoshida,Kazu-ichi
Kuwana,Shun-ichi
author_sort Matsumoto,Akiko
title Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
title_short Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
title_full Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
title_fullStr Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
title_full_unstemmed Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
title_sort effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique
publisher Sociedad de Biología de Chile
publishDate 2015
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100036
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