N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation
Voltage-dependent Ca2+ channels (VDCCs) play a crucial role in the spinal pain transduction. We previously reported that nociceptive mechanical stimuli to the rat hindpaw evoked two types of ventral root discharges that increased during stimulation (during-discharges) and after cessation of stimulat...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319305262 |
| _version_ | 1819112428543148032 |
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| author | Shohei Yamamoto Mitsuo Tanabe Hideki Ono |
| author_facet | Shohei Yamamoto Mitsuo Tanabe Hideki Ono |
| author_sort | Shohei Yamamoto |
| collection | DOAJ |
| description | Voltage-dependent Ca2+ channels (VDCCs) play a crucial role in the spinal pain transduction. We previously reported that nociceptive mechanical stimuli to the rat hindpaw evoked two types of ventral root discharges that increased during stimulation (during-discharges) and after cessation of stimulation (after-discharges). To explore the involvement of VDCCs in these ventral root discharges, several VDCC blockers were applied directly to the surface of the spinal cord. Spinalized rats were laminectomized. The fifth lumbar ventral root was sectioned and used for multi-unit efferent discharges recording. An agar pool was constructed on the first lumbar vertebra for drug application. Ethosuximide (a T-type VDCC blocker) had no effect on ventral root discharges. ω-Conotoxin GVIA (an N-type VDCC blocker) preferentially suppressed after-discharges. ω-Agatoxin IVA (a P/Q-type VDCC blocker), diltiazem, and verapamil (L-type VDCC blockers) nonselectively depressed both during- and after-discharges. The more selective L-type VDCC blocker nicardipine depressed only after-discharges and the depression was exhibited when nicardipine was microinjected into the dorsal horn, but not into the ventral horn. These findings suggested that N- and L-type VDCCs in the dorsal horn were involved in the generation of afterdischarges and these blockers might be useful for treatment of persistent pain that involves the spinal pathway. Keywords:: after-discharges, dorsal horn, L-type voltage-dependent Ca2+ channel, N-type voltage-dependent Ca2+ channel, spinal cord |
| first_indexed | 2024-12-22T04:13:21Z |
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| id | doaj.art-f0318ad4c1a24aa4ac564fc9eb029ea4 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-22T04:13:21Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-f0318ad4c1a24aa4ac564fc9eb029ea42022-12-21T18:39:29ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-0111918290N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical StimulationShohei Yamamoto0Mitsuo Tanabe1Hideki Ono2Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanLaboratory of Pharmacology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, JapanLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Corresponding author. hiono@phar.nagoya-cu.ac.jp on April 28, 2012 (in advance)Voltage-dependent Ca2+ channels (VDCCs) play a crucial role in the spinal pain transduction. We previously reported that nociceptive mechanical stimuli to the rat hindpaw evoked two types of ventral root discharges that increased during stimulation (during-discharges) and after cessation of stimulation (after-discharges). To explore the involvement of VDCCs in these ventral root discharges, several VDCC blockers were applied directly to the surface of the spinal cord. Spinalized rats were laminectomized. The fifth lumbar ventral root was sectioned and used for multi-unit efferent discharges recording. An agar pool was constructed on the first lumbar vertebra for drug application. Ethosuximide (a T-type VDCC blocker) had no effect on ventral root discharges. ω-Conotoxin GVIA (an N-type VDCC blocker) preferentially suppressed after-discharges. ω-Agatoxin IVA (a P/Q-type VDCC blocker), diltiazem, and verapamil (L-type VDCC blockers) nonselectively depressed both during- and after-discharges. The more selective L-type VDCC blocker nicardipine depressed only after-discharges and the depression was exhibited when nicardipine was microinjected into the dorsal horn, but not into the ventral horn. These findings suggested that N- and L-type VDCCs in the dorsal horn were involved in the generation of afterdischarges and these blockers might be useful for treatment of persistent pain that involves the spinal pathway. Keywords:: after-discharges, dorsal horn, L-type voltage-dependent Ca2+ channel, N-type voltage-dependent Ca2+ channel, spinal cordhttp://www.sciencedirect.com/science/article/pii/S1347861319305262 |
| spellingShingle | Shohei Yamamoto Mitsuo Tanabe Hideki Ono N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation Journal of Pharmacological Sciences |
| title | N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation |
| title_full | N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation |
| title_fullStr | N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation |
| title_full_unstemmed | N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation |
| title_short | N- and L-Type Voltage-Dependent Ca2+ Channels Contribute to the Generation of After-Discharges in the Spinal Ventral Root After Cessation of Noxious Mechanical Stimulation |
| title_sort | n and l type voltage dependent ca2 channels contribute to the generation of after discharges in the spinal ventral root after cessation of noxious mechanical stimulation |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319305262 |
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