Shocking the pain off

Electric fish have long disappeared from the medical armamentarium. And patients with headaches are most frequently treated with pharmaceuticals.

But recently, electrical or electromagnetic devices that hark back to the head-zapping torpedo fish have come into vogue among prominent migraine researchers.

Two different kinds of stimulatory devices are now in largescale clinical trials for the most severe cases. Many researchers believe that such devices are likely to play a greater role in migraine treatment in the future.

Dr Richard B Lipton, professor of neurology at the Albert Einstein College of Medicine and director of the Montefiore Headache Center, says while there are many drugs to treat the disorder or ward off the pain, some people do not respond to them or cannot tolerate the side effects. 8220;There is still a lot of unmet need. So the idea of having stimulatory devices is very attractive.8221;

The two kinds of stimulatory approaches now in large-scale clinical trials are Occipital Nerve Stimulation ONS, and Transcranial Magnetic Stimulation TMS.

In ONS, a pacemaker-like device connected to electrodes, is placed at the back of the head under the skin. Electrical current is delivered through the electrodes. In TMS, a magnetic device is pressed to the back of the head and brief pulses are delivered, altering electrical activity inside the brain in hopes of halting the migraine before it begins.

Experts say approaches like these represent a powerful new trend in migraine research. Some patients who have undergone the trial treatments say they helped.

Cheryl Myers, who lives near Columbus, Ohio, said for 10 years she suffered from chronic, disabling migraines that forced her to stop working. 8220;The only thing that helped was narcotics,8221; said Myers, 49. 8220;But I couldn8217;t be taking them three or four times a week.8221; In 2004, she enrolled in a clinical trial for ONS at the Michigan Head-Pain and Neurological Institute. The device was placed in her upper buttocks and connected through wires under skin to electrodes at the base of her neck, on either side.

Soon after the device was turned on, Myers said, she began having fewer migraines, and those were less severe. Within a few months, she was able to return to work.

Dr Joel R Saper, director of the institute, said the electrodes stimulate the greater occipital nerve, which runs along the back of the head on either side. The nerve converges in the upper or spinal cord with the trigeminal system, which includes neurons and neural pathways responsible for conveying the throbbing pain. Dr Saper says it is not clear how occipital nerve stimulation works. But one possibility is that it inhibits activity in the trigeminal system, dampening the pain.

Three companies are conducting large-scale clinical trials of three different ONS 8212; Advanced Neuromodulation Systems, a division of St. Jude Medical; Advanced Bionics, a Boston Scientific company; and Medtronic.

Though the studies are not over, Dr Saper said 8220;it is clear that some people get better, some people don8217;t.8221; The treatment was appropriate only for patients who did not respond to less invasive approaches.

As for TMS, Dr Yousef M Mohammad, neurologist at Ohio State University Medical Center, said preliminary research by his group and others indicated that this approach might be helpful to patients who experience an aura before developing a headache.

For those who experience an aura, a wave of electrical excitation appears to spread through an area of the brain called the occipital cortex. Because this area governs vision, patients may see flashing lights, dancing bright spots or wavy lines, or they may experience a blind spot in their vision. Intense excitation is soon followed by exhaustion or depression of the affected brain cells. The end result, known technically as 8220;cortical-spreading depression,8221; is irritation of trigeminal nerve fiber 8212; and a throbbing, pounding headache. The goal of TMS is to interfere with the initial wave of excitation, thereby preventing the headache. Roughly 20 per cent of migraine patients experience an aura, according to the US National Headache Foundation.

In a study of 43 patients conducted by Dr Mohammad and his colleagues in 2004 and 2005, 74 per cent said they had no headache or a mild headache afer the treatment. The California-based company Neuralieve has developed smaller, portable devices that resemble ray guns. These devices are being tested in the current trial. Depending on the result and FDA approval, a stimulator could be in the market in 18 months.

Dr Mohammad, who is on Neuralieve8217;s medical advisory board, said the idea of using electrical or electromagnetic stimulation to treat migraines resulted partly from a shift in how neurologists understood the disorder. Modern medicine has viewed migraines primarily as a vascular problem. Blood vessels in the brain constricted, then subsequently dilated, irritating the nerve endings around them and causing pulsating pain. More recently, however, scientists have come to view these vascular changes as secondary to underlying neural events.

Dr David W Dodick, professor of neurology at the Mayo Clinic, Arizona, said while the biology and treatment of migraine have come a long way in last 20 years, scientists needed to develop a better understanding of the mechanisms that initiate an attack.

Genetics are thought to play a major role and in those who are predisposed, migraine can occur spontaneously or be set off by a host of factors 8212; stress, noise, bright lights, changes in sleep patterns, certain foods and fluctuating estrogen levels, which may be why the disorder is about three times more common in women than men. But how these factors interact are not well understood. Once the basic science is better understood, it will be possible to develop pharmaceuticals that aim to prevent attacks without untoward side effects. 8220;That8217;s where I believe the future is,8221; he said.