A peptide whose absence leads to narcolepsy also might play role in pain sensation

February 01, 2002

New Haven, Conn. - A neuropeptide whose loss is believed responsible for narcolepsy, a disease characterized by sudden sleep attacks, also appears to play a role in the modulation of pain sensation, a study by a Yale researcher has found.

The findings, published as the cover story in the January issue of the Journal of Physiology, offers a new direction in the control of pain, particularly in spinal cord injuries where pain is a substantial problem, said Anthony van den Pol, professor of neurosurgery at Yale School of Medicine and co-author of the study. Collaborators in the study were Ed Perl and Tim Grudt from the University of North Carolina.

The researchers' findings indicate that hypocretin neurons from the hypothalamus establish direct connections with the spinal cord and hypocretin changes the electrical activity of nerve cells in the dorsal part of the spinal cord that are involved in pain perception. The hypothalamus is generally considered to be an area of the brain that regulates eating, drinking, sleeping, waking, body temperature, chemical balances, heart rate, hormones, sex and emotions.

"We found that most cells in a region of the spinal cord responsible for detecting pain show a significant physiological response to the peptide hypocretin-2," said van den Pol.

It was van den Pol's laboratory, along with colleagues at Stanford University and the Scripps Institute, that first described this new hypothalamic neurotransmitter in 1998. Subsequent studies showed that narcolepsy was caused by the selective neurodegeneration of the hypocretin system. Prior to that finding, narcolepsy was sometimes blamed on laziness or indistinct mental problems.

Van den Pol said the new findings show that in addition to hypocretin's role in enhancing arousal, the neurotransmitter may also modulate pain sensation.

He said more work is needed to establish the specific role of hypocretin in altering sensory input that includes pain and temperature sensation. In the future, new drugs related to hypocretin may prove useful in the treatment and reduction of pain.
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Yale University

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