Why opioid pain killers don't work.

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.

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.

Reference: The Journal of Neuroscience, Sept. 12, 2007, 27(37):10000--10006.
ScienceDaily (Oct. 3, 2007)

Chronic Pain Patients, CRPS 1 & 2

A debate is currently raging as to whether diagnoses, such as fibromyalgia and complex regional pain syndrome 1, can be classified as neuropathic. Our NPS cut-off score results suggest that these diagnoses may have a neuropathic pain component. The reliability and validity of our NPS method will need to be tested further in other neuropathic pain models, such as diabetic peripheral neuropathic pain.

Study Suggests Fibromyalgia Pain is Neuropathic

In the March issue of the journal Pain Medicine, researchers at three institutions in Florida conducted a study to determine whether the neuropathic pain scale (NPS) can be used to classify chronic pain patients (CPPs) as having primarily neuropathic vs non-neuropathic pain, as well as to determine whether there is a cut-off score that can be used reliably to make this distinction between types of pain. This study evaluated 305 chronic pain patients (CPPs) admitted to The Rosomoff Pain Center (Miami, FL). All were administered the NPS, a diagnostic tool designed to assess the distinct pain qualities associated with neuropathic pain, and were given a diagnosis on the basis of a physical examination and all available test results.

Using patients known to have neuropathic or non-neuropathic pain conditions as a reference, esearchers were able to derive "an NPS cut-off score above which CPPs would be classified as having neuropathic pain." Patients who had diagnoses of myofascial pain syndromes, spinal stenosis, epidural fibrosis, fibromyalgia, complex regional pain syndromes, and failed back surgery syndrome, a predicted NPS score was calculated and compared with the cut-off score.

The NPS appeared to be able to separate CPPs into neuropathic pain vs non-neuropathic pain subtypes. The cut-off score the researchers derived was 5.53 on the NPS. Myofascial pain syndrome and spinal stenosis had scores lower than this cut-off score at 3.81 and 4.26, respectively - Therefore they did not meet the criteria for neuropathic pain. Epidural fibrosis, fibromyalgia, complex regional pain syndromes, and failed back surgery syndrome had predictive scores higher than the cut-off score at 6.15, 6.35, 6.87, 9.34, and 7.19, respectively. Thus, these syndromes did meet the qualifications for neuropathic pain according to this study's criteria. The researchers conclude that the NPS does appear to be able to discriminate between patients experiencing neuropathic and non-neuropathic pain.

Pain Medicine, Vol. 9, No. 2. (March 2008), pp. 149-160.

David A. Fishbain MDFAPA, John E. Lewis PhD, Robert Cutler PhD, Brandly Cole PsyD, Hubert L. Rosomoff MDDMedScFAAPM, Rennée S. Rosomoff BSNMBA (2008)
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1526-4637.2007.00302.x

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