New therapies are being tried for chronic pain

Washington -- Pain and what to do about it is a major headache -- not to mention backache, stomachache and so forth. Usually it eventually goes away, but sometimes it doesn't. That's chronic pain -- and that's bad.

Pain is frequently the reason behind a physician visit, yet it is often underdiagnosed and undertreated, said Sean Mackey, MD, PhD, associate director of the Stanford University Pain Management Center in Stanford, Calif.

Diabetic peripheral neuropathy is one example of a painful, life-altering condition that affects nearly one-half of all diabetic patients, particularly those who have poor glycemic control, said Dr. Mackey, speaking at the AMA's 24th annual Science Reporters' Conference held Nov. 10 in Washington, D.C.

The pain often starts in the hands or feet and slowly extends up the arm or leg, he said. If left unchecked, the pain will continue to progress. Yet it, too, is frequently left untreated, he said.

Pain is often with us. It is estimated that about 50 million Americans are affected. It's the most common presenting symptom for hospital admission after fever. This problem also damages the nation's economy, costing $61 billion dollars a year in time lost from work.

"Chronic pain in general has a huge impact on people's lives," said Dr. Mackey. "It causes depression. It causes anxiety." It can even lead to suicide.

The need to pay heed to it and its many causes also has been a concern of the National Institutes of Health, which has established a pain consortium that stretches across its institutes and centers.

The consortium promotes collaboration among researchers to address pain mechanisms, management of pain, cancer pain, joint and muscle pain, musculoskeletal pain, drug delivery and addiction.

Several NIH researchers presented findings on how to treat and diagnose pain at a Nov. 2 briefing.

There is an arsenal of treatments physicians can enlist for pain, including duloxetine and pregabalin, newly approved by the Food and Drug Administration for the treatment of diabetic neuropathy.

Many of the current pain medications have been borrowed from other fields, Dr. Mackey noted. Duloxetine, for example, is an antidepressant.

Methadone also has been useful for relieving pain in some people, said Ann O'Mara, PhD, program director at the National Cancer Institute, although it is not recommended for daily use because of its long half-life.

Other, more commonly utilized pain relievers include analgesics such as acetaminophen, NSAIDS and opioids; adjuvants such as the anticonvulsant gabapentin; additional antidepressants such as amtriptyline; steroids such as prednisone; anti-adrenergics such as clonidine; and local anesthetics such as the Lidoderm patch.

There also are common principles of good pain management that should be followed, said Andrew J. Mannes, MD, senior staff researcher at NIH's National Institute of Dental and Craniofacial Research.

They include using the most simple, safe and effective schedule of medication administered via the least invasive route, prescribing the least amount of medication needed for satisfactory results, considering the emotional issues associated with pain and using the World Health Organization's ladder of medications. This scale was developed with cancer pain in mind and it includes steps from aspirin to strong opioids.

In the cases of patients with diabetic neuropathy, education is crucial, Dr. Mackey said. Good control of blood sugar is essential. For their pain relief, a multidisciplinary approach is employed that includes physical therapy to increase strength and encourage weight loss. In addition, taking pain medications at specific times during the day and not just when pain occurs is recommended.

Various psychosocial interventions also are useful, Dr. O'Mara said. They include hypnosis and training in coping skills such as how to report pain symptoms adequately to physicians. There also are ongoing trials assessing the benefit of massage and acupuncture.

Dr. Mannes believes a good patient history is vital to delivering the proper treatment. But it does take time. He allows as long as an hour to talk to a patient before prescribing a medication for pain relief.

The cutting edge

Several clinical trials are under way to test drugs specifically targeted to relieve cancer pain. The trials include the Lidocaine patch for post-operative neuropathy and irradiation for bone metastasis.

Other studies are aimed at helping physicians better employ existing protocols and practice guidelines, Dr. O'Mara said.

But since even the strongest opioids might not work for everyone, Michael J. Iadarola, PhD, a senior investigator at NIDCR, and colleagues are exploring ways to disable cells that respond to pain.

One agent that has been effective in rats and dogs is derived from a plant, Euphorbia resinifera, which grows on hillsides in Morocco. Phase 1 clinical trials are next.

Jeffrey S. Mogil, PhD, Canada Research Chair in the Genetics of Pain at McGill University in Montreal, is exploring the variability in pain sensitivity. "Why," he asked, "do only 1% to 15% of patients receiving a major peripheral nerve injury develop chronic pain?"

Is it the particularities of the injury? Something about the individual who was injured? Or is it a combination of both? In studies a few years ago, Dr. Mogil and colleagues nailed down the genetics theory when they showed that women with red hair, fair skin and freckles responded better to a certain painkiller.

The finding is important, he said, because establishing a genetic determinant for pain could lift the stigma from pain-sensitive individuals. Pain treatment is also more likely to become individualized, new pain-related proteins are more likely to be discovered, and gene therapy is more likely to be sought for chronic pain.