Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia

Yeong-Ray Wen, Marc R. Suter, Ru Rong Ji, Geng Chang Yeh, Yen Sheng Wu, Kuo Ching Wang, Tatsuro Kohno, Wei Zen Sun, Chia Chuan Wang

研究成果: 雜誌貢獻文章

91 引文 (Scopus)

摘要

BACKGROUND: Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision. METHODS: After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain. RESULTS: A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38 was found predominantly in microglia. However, microglial activation (assessed by OX-42 upregulation) was not evident until 3 days after plantar incision. Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat hyperalgesia at an early time point. CONCLUSIONS: Plantar incision-induced mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating postsurgical pain.
原文英語
頁(從 - 到)155-165
頁數11
期刊Anesthesiology
110
發行號1
DOIs
出版狀態已發佈 - 一月 2009

指紋

Hyperalgesia
Microglia
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Hot Temperature
Posterior Horn Cells
Neuralgia
Postoperative Pain
Up-Regulation
Pain

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

引用此文

Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia. / Wen, Yeong-Ray; Suter, Marc R.; Ji, Ru Rong; Yeh, Geng Chang; Wu, Yen Sheng; Wang, Kuo Ching; Kohno, Tatsuro; Sun, Wei Zen; Wang, Chia Chuan.

於: Anesthesiology, 卷 110, 編號 1, 01.2009, p. 155-165.

研究成果: 雜誌貢獻文章

Wen, Y-R, Suter, MR, Ji, RR, Yeh, GC, Wu, YS, Wang, KC, Kohno, T, Sun, WZ & Wang, CC 2009, 'Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia', Anesthesiology, 卷 110, 編號 1, 頁 155-165. https://doi.org/10.1097/ALN.0b013e318190bc16
Wen, Yeong-Ray ; Suter, Marc R. ; Ji, Ru Rong ; Yeh, Geng Chang ; Wu, Yen Sheng ; Wang, Kuo Ching ; Kohno, Tatsuro ; Sun, Wei Zen ; Wang, Chia Chuan. / Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia. 於: Anesthesiology. 2009 ; 卷 110, 編號 1. 頁 155-165.
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abstract = "BACKGROUND: Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision. METHODS: After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain. RESULTS: A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38 was found predominantly in microglia. However, microglial activation (assessed by OX-42 upregulation) was not evident until 3 days after plantar incision. Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat hyperalgesia at an early time point. CONCLUSIONS: Plantar incision-induced mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating postsurgical pain.",
author = "Yeong-Ray Wen and Suter, {Marc R.} and Ji, {Ru Rong} and Yeh, {Geng Chang} and Wu, {Yen Sheng} and Wang, {Kuo Ching} and Tatsuro Kohno and Sun, {Wei Zen} and Wang, {Chia Chuan}",
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T1 - Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia

AU - Wen, Yeong-Ray

AU - Suter, Marc R.

AU - Ji, Ru Rong

AU - Yeh, Geng Chang

AU - Wu, Yen Sheng

AU - Wang, Kuo Ching

AU - Kohno, Tatsuro

AU - Sun, Wei Zen

AU - Wang, Chia Chuan

PY - 2009/1

Y1 - 2009/1

N2 - BACKGROUND: Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision. METHODS: After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain. RESULTS: A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38 was found predominantly in microglia. However, microglial activation (assessed by OX-42 upregulation) was not evident until 3 days after plantar incision. Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat hyperalgesia at an early time point. CONCLUSIONS: Plantar incision-induced mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating postsurgical pain.

AB - BACKGROUND: Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision. METHODS: After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain. RESULTS: A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38 was found predominantly in microglia. However, microglial activation (assessed by OX-42 upregulation) was not evident until 3 days after plantar incision. Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat hyperalgesia at an early time point. CONCLUSIONS: Plantar incision-induced mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating postsurgical pain.

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