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Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation

BACKGROUND: Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. METHODS: Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underw...

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Autores principales: Cheng, Kuang-I, Lai, Chung-Sheng, Wang, Fu-Yuan, Wang, Hung-Chen, Chang, Lin-Li, Ho, Shung-Tai, Tsai, Hung-Pei, Kwan, Aij-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141398/
https://www.ncbi.nlm.nih.gov/pubmed/21676267
http://dx.doi.org/10.1186/1471-2377-11-71
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author Cheng, Kuang-I
Lai, Chung-Sheng
Wang, Fu-Yuan
Wang, Hung-Chen
Chang, Lin-Li
Ho, Shung-Tai
Tsai, Hung-Pei
Kwan, Aij-Li
author_facet Cheng, Kuang-I
Lai, Chung-Sheng
Wang, Fu-Yuan
Wang, Hung-Chen
Chang, Lin-Li
Ho, Shung-Tai
Tsai, Hung-Pei
Kwan, Aij-Li
author_sort Cheng, Kuang-I
collection PubMed
description BACKGROUND: Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. METHODS: Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L(6 )transverse process; (2) ligated (Group L), which underwent left L(5 )spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L(5 )SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav(1.3 )and Nav(1.8)) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD(3)) and 7 (POD(7)). RESULTS: Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav(1.3 )and down-regulation of Nav(1.8), and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD(3), palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav(1.3 )up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD(7 )(p = 0.002). CONCLUSIONS: Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav(1.3 )up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain.
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spelling pubmed-31413982011-07-23 Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation Cheng, Kuang-I Lai, Chung-Sheng Wang, Fu-Yuan Wang, Hung-Chen Chang, Lin-Li Ho, Shung-Tai Tsai, Hung-Pei Kwan, Aij-Li BMC Neurol Research Article BACKGROUND: Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. METHODS: Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L(6 )transverse process; (2) ligated (Group L), which underwent left L(5 )spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L(5 )SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav(1.3 )and Nav(1.8)) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD(3)) and 7 (POD(7)). RESULTS: Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav(1.3 )and down-regulation of Nav(1.8), and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD(3), palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav(1.3 )up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD(7 )(p = 0.002). CONCLUSIONS: Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav(1.3 )up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain. BioMed Central 2011-06-16 /pmc/articles/PMC3141398/ /pubmed/21676267 http://dx.doi.org/10.1186/1471-2377-11-71 Text en Copyright ©2011 Cheng et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cheng, Kuang-I
Lai, Chung-Sheng
Wang, Fu-Yuan
Wang, Hung-Chen
Chang, Lin-Li
Ho, Shung-Tai
Tsai, Hung-Pei
Kwan, Aij-Li
Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title_full Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title_fullStr Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title_full_unstemmed Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title_short Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav(1.3 )expression and decreasing spinal microglial activation
title_sort intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating nav(1.3 )expression and decreasing spinal microglial activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141398/
https://www.ncbi.nlm.nih.gov/pubmed/21676267
http://dx.doi.org/10.1186/1471-2377-11-71
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