Nov 5, 1999

Brain-derived TNFalpha mediates neuropathic pain

Brain Research
Tracey A IgnatowskiRobert N Spengler


Neuropathic pain is a chronic pain state that develops a central component following acute nerve injury. However, the pathogenic mechanisms involved in the expression of this central component are not completely understood. We have investigated the role of brain-associated TNF in the evolution of hyperalgesia in the chronic constriction injury (CCI) model of neuropathic pain. Thermal nociceptive threshold has been assessed in rats (male, Sprague-Dawley) that have undergone loose, chromic gut ligature placement around the sciatic nerve. Total levels of TNF in regions of the brain, spinal cord and plasma have been assayed (WEHI-13VAR bioassay). Bioactive TNF levels are elevated in the hippocampus. During the period of injury, hippocampal noradrenergic neurotransmission demonstrates a decrease in stimulated norepinephrine (NE) release, concomitant with elevated hippocampal TNF levels. Continuous intracerebroventricular (i.c.v.) microinfusion of TNF-antibodies (Abs) starting at four days, but not six days, following ligature placement completely abolishes the hyperalgesic response characteristic of this model, as assessed by the 58 degrees C hot-plate test. Antibody infusion does not decrease spinal cord or plasma levels of TNF. Co...Continue Reading

Mentioned in this Paper

Tumor Necrosis Factor-alpha
Structure of Sciatic Nerve
Pathogenic Organism
Malignant Neoplasm of Spinal Cord
SD, Rat Strain
Synaptic Transmission
Hot Temperature
Neoplasm of Uncertain or Unknown Behavior of Spinal Cord

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