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Inflammatory pain may help deter inflammatory diseases like arthritis

ving from the blood, through the lining of the blood vessels and into the tissue, and they begin this process by adhering to the lining of the blood vessels. L-selectin, expressed on the cells' surface, allows the cells to adhere to and slowly roll along this lining.

The crux of the UCSF finding was determining that activated pain fibers caused L-selectin to be shed from the neutrophils circulating in the blood, thereby preventing the white blood cells from accessing the inflammatory site. The mechanism by which L-selectin shedding inhibited neutrophil migration is not entirely clear, but the shedding did block the migration.

"We still must work out the specific mechanisms involved in this process," said Strausbaugh, "but activation of pain fibers does induce the shedding mechanism and is responsible for the observed inhibition of neutrophil accumulation." The researchers must also determine what hormone messenger is released into the blood in response to activity in pain nerve fibers to cause L-selectin shedding in the first place. The answer could lead to a future therapy.

"It may be that insufficient amounts of the hormone are released, or that receptors for the hormone are defective," said Strausbaugh. "If the problem was that the amount of the hormone was insufficient, therapy might be as simple as injecting the hormone into the blood stream."

Alternatively, she said, some people might have a defect in the pain nerve circuit that either prevents the pain fibers from being activated or that activates them too late.

Already, the finding is offering important insight into studies recently reported in humans. One investigation, conducted in patients with adult respiratory distress syndrome, associated with chronic bronchitis, asthma and emphysema, (Lancet, 344, 215-9, 1994), showed that patients who had low levels of L-selectin in the blood were sicker and died more often. As low levels of L-selectin in the blood indicate that few L-select
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
30-Aug-1999


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