Why Don't Painkillers Work For People With Fibromyalgia?
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9/27/2007




Science Daily People who have the common chronic pain condition
fibromyalgia often report that they don't respond to the types of
medication that relieve other people's pain.


New research from the University of Michigan Health System helps to
explain why that might be: Patients with fibromyalgia were found to
have reduced binding ability of a type of receptor in the brain that
is the target of opioid painkiller drugs such as morphine.

The study included positron emission tomography (PET) scans of the
brains of patients with fibromyalgia, and of an equal number of sex-
and age-matched people without the often-debilitating condition.
Results showed that the fibromyalgia patients had reduced mu-opioid
receptor (MOR) availability within regions of the brain that
normally process and dampen pain signals -- specifically, the
nucleus accumbens, the anterior cingulate and the amygdala.

"The reduced availability of the receptor was associated with
greater pain among people with fibromyalgia," says lead author
Richard E. Harris, Ph.D., research investigator in the Division of
Rheumatology at the U-M Medical School's Department of Internal
Medicine and a researcher at the U-M Chronic Pain and Fatigue
Research Center.

"These findings could explain why opioids are anecdotally thought to
be ineffective in people with fibromyalgia," he notes. The findings
appear in The Journal of Neuroscience. "The finding is significant
because it has been difficult to determine the causes of pain in
patients with fibromyalgia, to the point that acceptance of the
condition by medical practitioners has been slow."

Opioid pain killers work by binding to opioid receptors in the brain
and spinal cord. In addition to morphine, they include codeine,
propoxyphene-containing medications such as Darvocet, hydrocodone-
containing medications such as Vicodin, and oxycodone-containing
medications such as Oxycontin.

The researchers theorize based on their findings that, with the
lower availability of the MORs in three regions of the brains of
people with fibromyalgia, such painkillers may not be able to bind
as well to the receptors as they can in the brains of people without
the condition.

Put more simply: When the painkillers cannot bind to the receptors,
they cannot alleviate the patient's pain as effectively, Harris
says. The reduced availability of the receptors could result from a
reduced number of opioid receptors, enhanced release of endogenous
opioids (opioids, such as endorphins, that are produced naturally by
the body), or both, Harris says.

The research team also found a possible link with depression. The
PET scans showed that the fibromyalgia patients with more depressive
symptoms had reductions of MOR binding potential in the amygdala, a
region of the brain thought to modulate mood and the emotional
dimension of pain.

The study subjects were 17 women with fibromyalgia and 17 women
without the condition.

The senior author of the paper was Jon-Kar Zubieta, M.D., Ph.D., the
Phil F. Jenkins Research Professor of Depression in the U-M
Department of Psychiatry and a member of U-M's Molecular and
Behavioral Neuroscience Institute, Depression Center and Department
of Radiology. Other authors were Daniel J. Clauw, M.D.; David J.
Scott, Ph.D.; Samuel A. McLean, M.D., MPH; and Richard H. Gracely,
Ph.D.

The research was supported by grants from the Department of the
Army; the National Center for Research Resources, a component of the
National Institutes of Health; and the NIH. Harris was supported by
an NIH--National Center for Complementary and Alternative Medicine
Grant. McLean was supported by an NIH grant.

Reference: The Journal of Neuroscience, Sept. 12, 2007, 27(37):10000-
-10006.


Note: This story has been adapted from a news release issued by
University of Michigan Health System.


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2007 Science Daily