Oct 24, 2006

Antinociception mediated by alpha(2)-adrenergic activation involves increasing tumor necrosis factor alpha (TNFalpha) expression and restoring TNFalpha and alpha(2)-adrenergic inhibition of norepinephrine release

Robert N SpenglerTracey A Ignatowski


The central component that establishes chronic pain from peripheral nerve injury is associated with increased tumor necrosis factor-alpha (TNFalpha) production in the brain. This study examined TNFalpha and its reciprocally permissive role with alpha(2)-adrenergic activation during peak and progressive decline of thermal hyperalgesia in sciatic nerve chronic constriction injury (CCI). Accumulation of TNFalpha mRNA (in situ hybridization) increases in the hippocampus and locus coeruleus during the onset of neuropathic pain and persists as hyperalgesia abates. Activation of alpha(2)-adrenergic receptors in control rats decreases TNFalpha mRNA accumulation in these brain regions. In contrast, during hyperalgesia, alpha(2)-adrenergic activation enhances TNFalpha mRNA accumulation. Whether this enhanced TNFalpha production is associated with changes in the regulation of norepinephrine (NE) release was tested. Hippocampal slices were electrically depolarized to evaluate alpha(2)-adrenergic and TNFalpha regulation of NE release. While inhibition of NE release by TNFalpha is maximal during peak hyperalgesia, it subsequently transforms to facilitate NE release. In addition, alpha(2)-adrenergic receptor activation with clonidine (0.2mg/k...Continue Reading

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  • Citations11


Mentioned in this Paper

Salicylhydroxamic acid
Tissue Membrane
Tumor Necrosis Factor-alpha
Structure of Sciatic Nerve
Entire Brainstem
Visual Analog Pain Scale
Nucleic Acid Hybridization Procedure

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