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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Sociedad de Biología de Chile
2015
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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 |
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Scielo Chile |
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Scielo Chile |
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English |
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Carbamazepine Gabapentin Rat brainstem Spinal trigeminal nucleus Voltage-sensitive dye imaging |
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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 |
work_keys_str_mv |
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