| Paradoxically, the same
compound also may reduce pain. Capsaicin creams are natural
pain-relieving folk medicines, commonly found over the counter, and are
effective for a variety of pain syndromes, from minor muscle or joint
aches to those that are very difficult to treat, such as arthritis and
neuropathic pain.
Scientists at University at Buffalo now link the
analgesic effects of capsaicin to a lipid called PIP2 in the cell
membranes.
Results of the research, headed by Feng Qin, Ph.D.,
associate professor in the Department of Physiology and Biophysics in
the University at Buffalo's School of Medicine and Biomedical Sciences,
appear Feb. 24 in the journal PLoS Biology.
Capsaicin works by stimulating a receptor on nerve
endings in the skin, which sends a message to the brain and generates
the sensation of pain. The receptor also senses heat, making chili
peppers taste hot.
"The receptor acts like a gate to the neurons," said
Qin. "When stimulated it opens, letting outside calcium enter the cells
until the receptor shuts down, a process called desensitization. The
analgesic action of capsaicin is believed to involve this
desensitization process. However, how the entry of calcium leads to the
loss of sensitivity of the neurons was not clear."
Previous research from the UB group and others
implicated the significance of the PIP2 lipid. Calcium influx induces
strong depletion of the lipid in the plasma membrane. By combining
electrical and optical measurements, the authors now have been able to
directly link the depletion of PIP2 to the desensitization of the
receptor.
The authors also found that the receptor is still
fully functional after desensitization. "What changed was the
responsiveness threshold," said Qin. "In other words, the receptor had
not desensitized per se, but its responsiveness range was shifted. This
property, called adaptation, would allow the receptor to continuously
respond to varying stimuli over a large capsaicin concentration range."
"Adaptation" is a property that is found in other
sensory receptors, such as those in hearing and vision, and is
identified in pain receptors as well.
The findings have implications for pain-sensation
mechanisms as well as clinical applications, the authors note. With an
adaptive response, the receptors are essentially autoregulated without a
fixed threshold. The intensity that causes pain is dependent on the
history of activity.
Plasticity of pain is known at the central level. The
study now shows that it may also be present at the peripheral site,
although the sensation of pain is complex and involves many types of
receptors and messengers. The lipid dependence of the receptor also will
provide novel strategies for development of safe analgesics like
capsaicin, a natural pain reliever, but with less irritation.
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