NCC New Theories on Pain

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Hurt Your Finger? Treat Your Brain

Localized pain may not be so local after all

By Adam Marcus

HealthScout Reporter

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WEDNESDAY, March 21 (HealthScout) -- To understand how we feel pain, think of

a telephone call. Not a modern cell-phone call, mind you, but the

old-fashioned party line kind. We burn a finger, and irate local nerves dial

the brain direct and make their complaint, the theory goes. Neighboring

nerves also get into the act, becoming sensitive to touch, movement and other

stimuli they normally ignore. Two new studies suggest the systemic response

caused by a local wound, like a party-line telephone call, involves an

exchange of messages with the brain via molecules in the blood and spinal

fluid, as well as through nerves. Tony Yaksh, an anesthesiologist at the

University of California, San Diego, who's familiar with the research, has a

more high-tech name for the system, calling it a " world wide web " of pain and

swelling. And Yaksh says targeting the nervous system might ease pain

symptoms more directly and with fewer side effects than oral

anti-inflammatory drugs now on the market. The findings, reported in

tomorrow's issue of the journal Nature, center on a molecule called

cyclooxygenase-2, or cox-2, which is the target of anti-fever and painkilling

drugs, like non-steroidal anti-inflammatory medications (NSAIDs) and newer

compounds like Vioxx and Celebrex. Scientists long have known that cox-2

leads to hypersensitivity in the nerves around a local wound and in uninjured

tissue elsewhere, causing hyperalgesia, a condition which often includes

widespread pain, fever, achy joints and other symptoms far from the site of a

wound. Scientists say that reaction is because the body essentially is

curling up and licking its wounds. But only lately has it been well

understood. In the first study, led by Dr. Clifford Woolf of Harvard

University, researchers found that the spinal cord nerves of rats with

injured paws produced massive amounts of cox-2. So, too, did other parts of

the central nervous system, including several areas of the brain. When the

scientists blocked cox-2-by injecting drugs directly into the spinal column,

the injured rats showed much less hypersensitivity and hyperalgesia, the

study says. " We can never know what an animal feels, but there is remarkable

similarity in the changes in sensitivity these animal models display, " Woolf

says. The researchers also found high levels of an inflammatory hormone at

the site of the paw injury and in the animals' spinal fluid. " But we were

unable to show convincingly how [this hormone] in fluid was switched on, "

Woolf says. A second study, by Swedish scientists, may hold the answer. Dr.

Ek and colleagues at the Karolinska Institute in Stockholm showed that

injecting the hormone into the veins of rats triggers cells in the so-called

blood-brain barrier to generate both cox-2 and another inflammatory enzyme.

This barrier a sort of molecular sieve designed to protect the brain. These

molecules, in turn, can create a smaller inflammatory chemical that

penetrates the blood-brain wall and signals the cells beyond to start a

system-wide reaction that calls for more of the inflammatory hormone, turning

into a " vicious cycle, " Woolf says. " You're getting signaling of pain without

a direct nerve connection, " he says. Experts say the key to controlling

systemic pain reactions would be to develop oral drugs that muzzle cox-2 in

the central nervous system and prevent the cascade. The trouble, however, is

that most painkillers that affect cox-2 are too bulky to cross the protective

blood-brain barrier. However, Yaksh says the spinal cord is an excellent

target for painkillers because it conducts not only the direct nerve impulses

of pain, but also carries the inflammatory molecules that set off the

systemic reactions. What To Do To learn more about cox-2 blocking drugs,

visit the <A

HREF= " http://www.arthritis.org/answers/drugguide/nsaids_gut_protect.asp " >Arthrit\

is Foundation</A>. For more on NSAIDs, check the British health

site <A HREF= " http://www.medinfo.co.uk/drugs/nsaids.html " >Medinfo</A>.

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