[CH] Cap in pain research

Daniel Wright (daniel.wright@genetics.utah.edu)
Fri, 08 Jan 1999 14:11:28 -0700 

Dear heads,
This is excerpeted from the current issue of The Scientist.  It is from an
article titled Getting at the Moleculat Roots of Pain.
The entire text can be seen at
http://165.123.33.33/yr1999/jan/research_990104.html

The Role of Capsaicin

                                          When capsaicin binds to its
receptor, it opens a channel and excites the neuron, which then transmits
its pain signal. The same
                                          receptors are also located on
neurons that are activated by heat--hence the burning sensation associated
with a mouthful of hot chili
                                          peppers. 

                                          Stimulate capsaicin receptors and
a pain message is born. Such pain is a normal response--and will probably
stop you from rubbing
                                          your eyes next time you handle
jalapeņos. 

But what happens when you get sunburn? The area becomes exquisitely tender
and it hurts to touch it even lightly. This exaggerated sensitivity--called
sensitization--primes the pain pump and
causes neurons in the pain pathway to overreact to painful and sometimes
nonpainful stimuli. The process, triggered by inflammation or tissue
injury, is mediated in part by nerve growth factor
(NGF), which causes pain-sensing neurons to react more vigorously to
noxious stimuli, says Mendell. In fact, NGF may enhance the response of
sensory neurons by boosting the activity of
the capsaicin receptor, a finding that Mendell and X. Q. Shu presented at
the November meeting of the Society for Neuroscience. 

If researchers can figure out how to disable the capsaicin receptor, they
might be able to stop pain messages before they start. Which is what
Levine, Wendye Robbins, and their UCSF
colleagues have now done--using large doses of capsaicin itself. The
researchers found that overstimulating the receptor can actually reduce
clinical pain, perhaps by killing off the sensitive
tips of these neurons by overexciting them. 

The researchers treated people with chronic pain with high concentrations
of capsaicin--5 percent to 10 percent solutions. (To provide some
perspective, sporting goods stores market 1
percent capsaicin solutions as a grizzly bear repellent.) Robbins, an
anesthesiologist by trade, administered a local anesthetic before brushing
capsaicin onto the patients' skin to minimize the
burning sensation. The results, says Levine, were "extremely dramatic." Of
the 10 patients treated, nine experienced a substantial reduction in
pain--an effect that in some cases lasted for
months.2 

Although using capsaicin to eliminate pain might seem counterintuitive,
Levine says it actually makes sense. Think about eating lots of spicy food.
"After awhile, you can eat foods that
previously you couldn't get near your mouth without reaching for a glass of
water," he says. With continued stimulation, the painful sensation
diminishes. 

Of course, eliminating all pain is not the goal, says Mendell. "Nobody
thinks that if you step on a nail you shouldn't feel pain," he notes. And
people treated with capsaicin still feel acute pain,
says Levine. "If you stick them with a pin or pinch them, they feel it," he
notes. What they don't feel is the chronic, nagging pain that even morphine
couldn't touch. 

Long time Lurker
Dan Wright
Engineer
Dept. of Human Genetics
University of Utah
and
Utah Salt Flats Racing Association