A naturally produced pain reliever can exacerbate certain pain states rather than attenuate them in rodents, according to a paper in the December 2006 issue of Nature Neuroscience. The paper reports that an endogenous opioid -- a small protein that activates the same receptors as opium or morphine -- activates a different type of receptor to produce this effect.
Josephine Lai and colleagues studied dynorphin A, one of the endogenous opioids that normally act at opiate receptors to inhibit chronic pain. Elevated levels of dynorphin A are found in some chronic pain syndromes, such as that caused by nerve damage, but unlike other endogenous opioids, dynorphin A actually makes the pain worse. The authors now explain these puzzling results by showing that dynorphin A also activates bradykinin receptors in the spinal cord, which are known to cause hypersensitivity to pain. A drug that blocks bradykinin receptors protected against neuropathic pain, but only when dynorphin A was elevated. Mice lacking the bradykinin receptor also failed to show increased pain in response to dynorphin A.
These findings suggest that new opiate drugs should be evaluated in terms of their effects on bradykinin receptors -- as well as opiate receptors -- before being used to treat pain, and may prove useful in the development of novel approaches to drug development for chronic pain.
Josephine Lai (University of Arizona, Tucson, AZ, USA)
Abstract available online.
(C) Nature Neuroscience press release.
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