Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury.

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Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury. / Whitehead, Kevin; Smith, CG; Delaney, SA; Curnow, Stephen; Salmon, M; Hughes, JP; Chessell, IP.

In: Brain, Behaviour, and Immunity, Vol. 24, No. 4, 01.05.2010, p. 569-576.

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@article{000388dd38c947829956bacca1965ee7,
title = "Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury.",
abstract = "Spinal release of cytokines may play a critical role in the maladapted nociceptive signaling underlying chronic pain states. In order to investigate this biology, we have developed a novel 'high flux' intrathecal microdialysis approach in combination with multiplex bead-based immunoassay technology to concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity. In a first study, C-fiber strength electrical stimulation of the operated nerve in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux ( approximately 15-fold) that was significantly greater than that observed in the sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent stimulation, whereas TNFalpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked cytokine release of both IL-1beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our studies demonstrate the ability of a neurone-glia signaling mechanism to dynamically modulate this release and support a role of spinal IL-1beta in the phasic transmission of abnormal pain signals.",
keywords = "Microdialysis, Tumour necrosis factor alpha, Propentofylline, Pain, Neuroinflammation, Neuropathy, Interleukin",
author = "Kevin Whitehead and CG Smith and SA Delaney and Stephen Curnow and M Salmon and JP Hughes and IP Chessell",
year = "2010",
month = may,
day = "1",
doi = "10.1016/j.bbi.2009.12.007",
language = "English",
volume = "24",
pages = "569--576",
journal = "Brain, Behaviour, and Immunity",
issn = "0889-1591",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury.

AU - Whitehead, Kevin

AU - Smith, CG

AU - Delaney, SA

AU - Curnow, Stephen

AU - Salmon, M

AU - Hughes, JP

AU - Chessell, IP

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Spinal release of cytokines may play a critical role in the maladapted nociceptive signaling underlying chronic pain states. In order to investigate this biology, we have developed a novel 'high flux' intrathecal microdialysis approach in combination with multiplex bead-based immunoassay technology to concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity. In a first study, C-fiber strength electrical stimulation of the operated nerve in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux ( approximately 15-fold) that was significantly greater than that observed in the sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent stimulation, whereas TNFalpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked cytokine release of both IL-1beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our studies demonstrate the ability of a neurone-glia signaling mechanism to dynamically modulate this release and support a role of spinal IL-1beta in the phasic transmission of abnormal pain signals.

AB - Spinal release of cytokines may play a critical role in the maladapted nociceptive signaling underlying chronic pain states. In order to investigate this biology, we have developed a novel 'high flux' intrathecal microdialysis approach in combination with multiplex bead-based immunoassay technology to concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity. In a first study, C-fiber strength electrical stimulation of the operated nerve in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux ( approximately 15-fold) that was significantly greater than that observed in the sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent stimulation, whereas TNFalpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked cytokine release of both IL-1beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our studies demonstrate the ability of a neurone-glia signaling mechanism to dynamically modulate this release and support a role of spinal IL-1beta in the phasic transmission of abnormal pain signals.

KW - Microdialysis

KW - Tumour necrosis factor alpha

KW - Propentofylline

KW - Pain

KW - Neuroinflammation

KW - Neuropathy

KW - Interleukin

U2 - 10.1016/j.bbi.2009.12.007

DO - 10.1016/j.bbi.2009.12.007

M3 - Article

C2 - 20035858

VL - 24

SP - 569

EP - 576

JO - Brain, Behaviour, and Immunity

JF - Brain, Behaviour, and Immunity

SN - 0889-1591

IS - 4

ER -