Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 24, Issue 4, Pages 569-576Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2009.12.007
Keywords
Pain; Neuroinflammation; Neuropathy; Interleukin; Tumour necrosis factor alpha; Propentofylline; Microdialysis
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Funding
- GlaxoSmithKline, Harlow, UK
- Scientific Projects Committee of the Medical Faculty, University of Birmingham
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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)-1 beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N2O 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-1 beta efflux (similar to 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 TNF alpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7 days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1 beta, IL-6 and TNF alpha and prevented afferent stimulation-evoked cytokine release of both IL-1 beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1 beta, IL-6 and TNF alpha, 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-1 beta in the phasic transmission of abnormal pain signals. (C) 2010 Elsevier Inc. All rights reserved.
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