Newswise — Bethesda, Md. (August 19, 2015) — Fibromyalgia is characterized by chronic pain from no clear source. Patients with fibromyalgia frequently have sleep problems: Their deep sleep brain wave patterns are often disrupted by brain waves that correspond to wakefulness. Previous studies have suggested that these irregular wave patterns worsen and may cause the pain. In a new study in Journal of Neurophysiology, researchers constructed a computational model that recreated the sleep patterns observed in patients with fibromyalgia to understand how the abnormal patterns arose.
The research team focused on the molecular targets of sodium oxybate, a drug reported to improve sleep in patients with fibromyalgia. They found that altering the activity of three specific targets—GABAB currents, the potassium leak currents and hyperpolarization-activated thalamic currents—restored sleep patterns in their model. Surprisingly, altering just the potassium leak currents or the hyperpolarization-activated thalamic currents could also restore normal deep sleep wave patterns. According to the researchers, drugs acting on one of these targets in the thalamus, a region in the brain that regulates sleep, might be enough to prevent disrupted sleep and its related adverse effects and provide relief to patients with fibromyalgia. In addition, “since no animal models of fibromyalgia exist, our model provides a much-needed tool for understanding what makes current fibromyalgia drugs efficacious and for finding more effective drugs,” the researchers wrote.
The study “Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia” is published ahead-of-print in the Journal of Neurophysiology.
Note: You may read the full text of this study free HERE.
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Alpha-delta sleep is the abnormal intrusion of alpha activity (8-13 Hz oscillations) into the delta activity (1-4 Hz oscillations) that defines slow wave sleep. Alpha-delta sleep is especially prevalent in fibromyalgia patients and there is evidence suggesting that the irregularities in the sleep of these patients may cause the muscle and tissue pain that characterizes the disorder.
We constructed a biophysically realistic mathematical model of alpha-delta sleep. Imaging studies in fibromyalgia patients suggesting altered levels of activity in the thalamus motivated a thalamic model as the source of alpha activity. Since sodium oxybate helps to alleviate the symptoms of fibromyalgia and reduces the amount of alpha-delta sleep in fibromyalgia patients, we examined how changes in the molecular targets of sodium oxybate affected alpha-delta activity in our circuit.
Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity.
Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep. Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus; such drugs might have fewer side effects than drugs that act systemically.
Source: American Physiological Society News Release