Journal
NEUROSCIENCE
Volume 103, Issue 2, Pages 529-539Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(00)00574-1
Keywords
cytokines; interleukin-6; microglia; astrocytes; nociception
Categories
Funding
- NIDA NIH HHS [F31 DA05969, DA11276] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA011276, F31DA005969] Funding Source: NIH RePORTER
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The expression of interleukin-1 beta and tumor necrosis factor has previously been shown to be up-regulated in the spinal cord of several rat mononeuropathy models. This present study was undertaken to determine whether blocking the action of central interleukin-1 beta and tumor necrosis factor attenuates mechanical allodynia in a gender-specific manner in a rodent L5 spinal nerve transection model of neuropathic pain, and whether this inhibition occurs via down-regulation of the central cytokine cascade or blockade of glial activation. Interleukin-1 receptor antagonist or soluble tumor necrosis factor receptor was administered intrathecally via lumbar puncture to male Holtzman rats in a preventative pain strategy, in which therapy was initiated 1 h prior to surgery. Administration of soluble tumor necrosis factor receptor attenuated mechanical allodynia, while interleukin-1 receptor antagonist alone was unable to decrease allodynia. Interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor, administered to both male and female rats in a preventative pain strategy, significantly reduced mechanical allodynia in a dose-dependent manner (P < 0.01). The magnitude of attenuation in allodynia was similar in both males and females. Immunohistochemistry on LS spinal cord revealed similar astrocytic and microglial activation regardless of treatment. At days 3 and 7 post-transection, animals receiving daily interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibited significantly less interleukin-6, but not interleukin-1, in the L5 spinal cord compared to vehicle-treated animals. In an existing pain paradigm, in which treatment was initiated on day 7 post-transection, interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor attenuated mechanical allodynia (P < 0.05) in male rats. These findings further support a role for central interleukin-1 and tumor necrosis factor in the development and maintenance of neuropathic pain through induction of a proinflammatory cytokine cascade. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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