Norepinephrine acts similarly to adrenaline, which is released from the adrenal gland in response to arousal and stress, such as might occur during combat, for example. Increases in adrenaline enable persons to perform necessary functions in spite of increased fear or stress. "Our laboratory has evidence that constant painful stimulation, such as occurs from back injury, may make neurons that normally inhibit pain when exposed to norepinephrine actually enhance pain in the presence of norepinephrine," said Spengler.
In this study, the researchers found that this change from pain inhibitor to pain facilitator is caused by increased production of TNF in the brain during chronic pain, and that this increase in TNF, in turn, caused neurons to decrease their release of norepinephrine. An imbalance of this neurotransmitter also is linked directly to symptoms of depression.
By manipulating the amount of TNF in this animal model of chronic pain and monitoring release of norepinephrine, as well as behavioral responses to pain, the researchers were able to mimic these cellular changes in the rat brain and produce the same changes that take place when naturally occurring chronic pain develops.
By administering the antidepressant drug, they showed that the drug causes a decrease in TNF and an increase in norepinephrine release, resulting in a decrease in pain and its symptoms.
"These findings provide novel information concerning this proinflammatory protein," said Spengler. "Not only have we shown that neurons make TNF, we've shown that norepinephrine regulates TNF, and vice versa, suggesting a physiologic role for TNF.
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Contact: Lois Baker
ljbaker@buffalo.edu
716-645-5000 x1417
University at Buffalo
10-Nov-2003