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Noradrenergic Dysfunction: A Model of Fibromyalgia Pain

In a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and co-funded by the NIH's Office of Research on Women's Health, lead investigator Luc Jasmin, MD, PhD, examined the role of noradrenaline (norepinephrine) in chronic pain by studying mice lacking this neurotransmitter throughout their bodies and rats lacking it in their brains and spinal cords.

Noradrenaline, a substance in the body that functions as both a stress hormone and a neurotransmitter (a chemical messenger), is important for many body functions, including the regulation of pain. Some researchers hypothesize that fibromyalgia is somehow linked to a lack of noradrenaline, yet medications that act on noradrenaline have only been a limited success for treating chronic pain syndromes.

To better understand the role of noradrenaline in chronic pain, Dr. Jasmin and a team of researchers studied pain response in rodents that lacked the hormone and neurotransmitter. The team used mice that had been genetically altered to lack noradrenaline before birth. The team also used adult rats, giving them a drug that wipes out the noradrenaline-producing cells in the central nervous system.

Both the mice and the rats had lower pain thresholds than animals with normal noradrenaline levels. The effect of treatment on pain thresholds was less pronounced for the rats than the mice. This result may be due to the fact that the rats' noradrenaline levels were depleted later in life, as adults - a scenario that more closely mimics what might occur in humans than the mouse model. (Human beings are rarely born without noradrenaline. It is necessary for fetal development.)

In rats, as in people with fibromyalgia, drugs designed to act on noradrenaline had little effect on pain, suggesting that although a noradrenaline deficit probably plays a role in chronic pain, other chemical anomalies in pain circuits also may play a critical role in the condition.