Reversal of experimental neuropathic pain by T-type calcium channel blockers

Ahmet Dogrul, Luis R. Gardell, Michael H. Ossipov, F. Cankat Tulunay, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Experimental nerve injury results in exaggerated responses to tactile and thermal stimuli that resemble some aspects of human neuropathic pain. Neuronal hyperexcitability and neurotransmitter release have been suggested to promote such increased responses to sensory stimuli. Enhanced activity of Ca 2+ current is associated with increased neuronal activity and blockade of N- and P-types, but not L-type, calcium channels have been found to block experimental neuropathic pain. While T-type currents are believed to promote neuronal excitability and transmitter release, it is unclear whether these channels may also contribute to the neuropathic state. Rats were prepared with L5/L6 spinal nerve ligation, and tactile and thermal hypersensitivities were established. Mibefradil or ethosuximide was administered either intraperitoneally, intrathecally (i.th.), or locally into the plantar aspect of the injured hindpaw. Systemic mibefradil or ethosuximide produced a dose-dependent blockade of both tactile and thermal hypersensitivities in nerve-injured rats; responses of sham-operated rats were unchanged. Local injection of mibefradil also blocked both end points. Ethosuximide, however, was inactive after local administration, perhaps reflecting its low potency when compared with mibefradil. Neither mibefradil nor ethosuximide given i.th. produced any blockade of neuropathic behaviors. The results presented here suggest that T-type calcium channels may play a role in the expression of the neuropathic state. The data support the view that selective T-type calcium channel blockers may have significant potential in the treatment of neuropathic pain states.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalPain
Volume105
Issue number1-2
DOIs
StatePublished - Sep 2003

Fingerprint

Mibefradil
T-Type Calcium Channels
Ethosuximide
Calcium Channel Blockers
Neuralgia
Touch
Hot Temperature
Hypersensitivity
L-Type Calcium Channels
Spinal Nerves
Ligation
Neurotransmitter Agents
Injections
Wounds and Injuries

Keywords

  • Neuropathic pain
  • Rat
  • T-type voltage sensing calcium channels

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Dogrul, A., Gardell, L. R., Ossipov, M. H., Tulunay, F. C., Lai, J., & Porreca, F. (2003). Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain, 105(1-2), 159-168. https://doi.org/10.1016/S0304-3959(03)00177-5

Reversal of experimental neuropathic pain by T-type calcium channel blockers. / Dogrul, Ahmet; Gardell, Luis R.; Ossipov, Michael H.; Tulunay, F. Cankat; Lai, Josephine; Porreca, Frank.

In: Pain, Vol. 105, No. 1-2, 09.2003, p. 159-168.

Research output: Contribution to journalArticle

Dogrul, A, Gardell, LR, Ossipov, MH, Tulunay, FC, Lai, J & Porreca, F 2003, 'Reversal of experimental neuropathic pain by T-type calcium channel blockers', Pain, vol. 105, no. 1-2, pp. 159-168. https://doi.org/10.1016/S0304-3959(03)00177-5
Dogrul, Ahmet ; Gardell, Luis R. ; Ossipov, Michael H. ; Tulunay, F. Cankat ; Lai, Josephine ; Porreca, Frank. / Reversal of experimental neuropathic pain by T-type calcium channel blockers. In: Pain. 2003 ; Vol. 105, No. 1-2. pp. 159-168.
@article{32c74ed0457d4ba29b95db0aba3030df,
title = "Reversal of experimental neuropathic pain by T-type calcium channel blockers",
abstract = "Experimental nerve injury results in exaggerated responses to tactile and thermal stimuli that resemble some aspects of human neuropathic pain. Neuronal hyperexcitability and neurotransmitter release have been suggested to promote such increased responses to sensory stimuli. Enhanced activity of Ca 2+ current is associated with increased neuronal activity and blockade of N- and P-types, but not L-type, calcium channels have been found to block experimental neuropathic pain. While T-type currents are believed to promote neuronal excitability and transmitter release, it is unclear whether these channels may also contribute to the neuropathic state. Rats were prepared with L5/L6 spinal nerve ligation, and tactile and thermal hypersensitivities were established. Mibefradil or ethosuximide was administered either intraperitoneally, intrathecally (i.th.), or locally into the plantar aspect of the injured hindpaw. Systemic mibefradil or ethosuximide produced a dose-dependent blockade of both tactile and thermal hypersensitivities in nerve-injured rats; responses of sham-operated rats were unchanged. Local injection of mibefradil also blocked both end points. Ethosuximide, however, was inactive after local administration, perhaps reflecting its low potency when compared with mibefradil. Neither mibefradil nor ethosuximide given i.th. produced any blockade of neuropathic behaviors. The results presented here suggest that T-type calcium channels may play a role in the expression of the neuropathic state. The data support the view that selective T-type calcium channel blockers may have significant potential in the treatment of neuropathic pain states.",
keywords = "Neuropathic pain, Rat, T-type voltage sensing calcium channels",
author = "Ahmet Dogrul and Gardell, {Luis R.} and Ossipov, {Michael H.} and Tulunay, {F. Cankat} and Josephine Lai and Frank Porreca",
year = "2003",
month = "9",
doi = "10.1016/S0304-3959(03)00177-5",
language = "English (US)",
volume = "105",
pages = "159--168",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Reversal of experimental neuropathic pain by T-type calcium channel blockers

AU - Dogrul, Ahmet

AU - Gardell, Luis R.

AU - Ossipov, Michael H.

AU - Tulunay, F. Cankat

AU - Lai, Josephine

AU - Porreca, Frank

PY - 2003/9

Y1 - 2003/9

N2 - Experimental nerve injury results in exaggerated responses to tactile and thermal stimuli that resemble some aspects of human neuropathic pain. Neuronal hyperexcitability and neurotransmitter release have been suggested to promote such increased responses to sensory stimuli. Enhanced activity of Ca 2+ current is associated with increased neuronal activity and blockade of N- and P-types, but not L-type, calcium channels have been found to block experimental neuropathic pain. While T-type currents are believed to promote neuronal excitability and transmitter release, it is unclear whether these channels may also contribute to the neuropathic state. Rats were prepared with L5/L6 spinal nerve ligation, and tactile and thermal hypersensitivities were established. Mibefradil or ethosuximide was administered either intraperitoneally, intrathecally (i.th.), or locally into the plantar aspect of the injured hindpaw. Systemic mibefradil or ethosuximide produced a dose-dependent blockade of both tactile and thermal hypersensitivities in nerve-injured rats; responses of sham-operated rats were unchanged. Local injection of mibefradil also blocked both end points. Ethosuximide, however, was inactive after local administration, perhaps reflecting its low potency when compared with mibefradil. Neither mibefradil nor ethosuximide given i.th. produced any blockade of neuropathic behaviors. The results presented here suggest that T-type calcium channels may play a role in the expression of the neuropathic state. The data support the view that selective T-type calcium channel blockers may have significant potential in the treatment of neuropathic pain states.

AB - Experimental nerve injury results in exaggerated responses to tactile and thermal stimuli that resemble some aspects of human neuropathic pain. Neuronal hyperexcitability and neurotransmitter release have been suggested to promote such increased responses to sensory stimuli. Enhanced activity of Ca 2+ current is associated with increased neuronal activity and blockade of N- and P-types, but not L-type, calcium channels have been found to block experimental neuropathic pain. While T-type currents are believed to promote neuronal excitability and transmitter release, it is unclear whether these channels may also contribute to the neuropathic state. Rats were prepared with L5/L6 spinal nerve ligation, and tactile and thermal hypersensitivities were established. Mibefradil or ethosuximide was administered either intraperitoneally, intrathecally (i.th.), or locally into the plantar aspect of the injured hindpaw. Systemic mibefradil or ethosuximide produced a dose-dependent blockade of both tactile and thermal hypersensitivities in nerve-injured rats; responses of sham-operated rats were unchanged. Local injection of mibefradil also blocked both end points. Ethosuximide, however, was inactive after local administration, perhaps reflecting its low potency when compared with mibefradil. Neither mibefradil nor ethosuximide given i.th. produced any blockade of neuropathic behaviors. The results presented here suggest that T-type calcium channels may play a role in the expression of the neuropathic state. The data support the view that selective T-type calcium channel blockers may have significant potential in the treatment of neuropathic pain states.

KW - Neuropathic pain

KW - Rat

KW - T-type voltage sensing calcium channels

UR - http://www.scopus.com/inward/record.url?scp=0141850350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141850350&partnerID=8YFLogxK

U2 - 10.1016/S0304-3959(03)00177-5

DO - 10.1016/S0304-3959(03)00177-5

M3 - Article

VL - 105

SP - 159

EP - 168

JO - Pain

JF - Pain

SN - 0304-3959

IS - 1-2

ER -