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Chronic Pain: Hope Through Research
New And Old Drugs For Pain

National Institute of Neurological Disorders and Stroke

September, 1997

When you complain of headache or low back pain and the doctor says take two aspirins every 4 hours and stay in bed, you may think your pain is being dismissed lightly. Not at all. Aspirin, one of the most universally used medications is an excellent painkiller. Scientists still cannot explain all the ways aspirin works, but they do know that it interferes with pain signals where they usually originate, at the nociceptive nerve endings outside the brain and spinal cord: peripheral nerves. Aspirin also inhibits the production of chemicals manufactured in the blood to promote blood clotting and wound healing: Prostaglandins. Unfortunately, prostaglandins, released from cells at the site of injury, are pain-causing substances. They actually sensitize nerve endings, making them -- and you -- feel more pain Along with increasing the blood supply to the area, the chemicals contribute to inflammation -- the pain, heat, redness and swelling of tissue damage.

Some investigators now think that the continued release of pain-causing substances in chronic pain conditions may lead to long-term nervous system changes in some patients that make them hypersensitive to pain. People suffering such hyperalgesia can cry out in pain at the gentlest touch, or even when a soft breeze blows over the affected area. In addition to the prostaglandins, blister fluid and certain insect and snake venoms also contain pain-causing substances. Presumably these chemicals alert you to the need for care-a fine reaction in an emergency, but not in chronic pain.

There are several prescription drugs that usually can provide stronger pain relief than aspirin. These include the opiate-related compounds codeine, propoxyphene (Darvon®), morphine, and meperidine (Demerol®). All these drugs have some potential for abuse, and may have unpleasant and even harmful side effects. In combination with other medications or alcohol, some can be dangerous. Used wisely, however, they are important recruits in the chemical fight against pain.

In the search for effective analgesics physicians have discovered pain-relieving benefits from drugs not normally prescribed for pain. Certain antidepressants as well as antiepileptic drugs are used to treat several particularly severe pain conditions, notably the pain of shingles and of facial neuralgias like tic douloureux.

Interestingly, pain patients who benefit from anti-depressants report pain relief before any uplift in mood. Pain specialists think that the antidepressant works because it increases the supply of a naturally produced neurotransmitter, serotonin. (Doctors have long associated decreased amounts of serotonin with severe depression.) But now scientists have evidence that cells using serotonin are also an integral part of a pain-controlling pathway that starts with endorphin-rich nerve cells high up in the brain and ends with inhibition of pain-conducting nerve cells lower in the brain or spinal cord. Antidepressant drugs have been used successfully in treating the excruciating pain that can follow an attack of shingles.

Antiepileptic drugs have been used successfully in treating tic douloureux, the riveting attacks of facial pain that affect older adults. The rationale for the use of the antiepileptic drugs (principally carbamazepine -- Tegretol®) does not involve the endorphin system. It is based on the theory that a healthy nervous system depends on a proper balance of incoming and outgoing nerve signals. Tic and other facial pains or neuralgias are thought to result from damage to facial nerves. That means that the normal flow of messages to and from the brain is disturbed. The nervous system may react by becoming hypersensitive: It may create its own powerful discharge of nerve signals, as though screaming to the outside world "Why aren't you contacting me?" Antiepileptic drugs -- used to quiet the excessive brain discharges associated with epileptic seizures -- quiet the distress signals associated with tic and may relieve pain that way.

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