Mar 18, 2000

Brain-derived TNFalpha: involvement in neuroplastic changes implicated in the conscious perception of persistent pain

Brain Research
W C CoveyR N Spengler


The pleiotropic cytokine tumor necrosis factor-alpha (TNFalpha) is implicated in the development of persistent pain through its actions in the periphery and in the central nervous system (CNS). Activation of the alpha(2)-adrenergic receptor is associated with modulation of pain, possibly through its autoregulatory effect on norepinephrine (NE) release in the CNS. The present study employs a chronic constriction nerve injury (CCI) pain model to demonstrate the interactive role of presynaptic sensitivity to TNFalpha and the alpha(2)-adrenergic autoreceptor in the pathogenesis of neuropathic pain. Accumulation of TNFalpha is increased initially in a region of the brain containing the locus coeruleus (LC) at day 4 post-ligature placement, followed by an increase in TNFalpha in the hippocampus at day 8 post-ligature placement, coincident with hyperalgesia. Levels of TNFalpha in the thoraco-lumbar spinal cord are also increased at day 8 post-ligature placement. Concurrently, alpha(2)-adrenergic receptor and TNFalpha-induced inhibition of NE release are increased, and stimulated NE release is decreased in superfused hippocampal slices isolated at day 8 post-ligature placement. Stimulated NE release is also decreased in spinal cord sli...Continue Reading

Mentioned in this Paper

Pathogenic Aspects
Pain, Intractable
Tumor Necrosis Factor-alpha
Entire Lumbar Spinal Cord
Malignant Neoplasm of Spinal Cord
Chronic Disease
Neoplasm of Uncertain or Unknown Behavior of Spinal Cord
Adrenergic alpha-Agonists

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