Much chronic pain is little understood but the key to a cure seems to lie in the brain, argues Ronald Melzack.

"Stop pain" has become a rallying cry for people who seek improved care for countless patients suffering agony associated with cancer, arthritis, nerve injuries or other causes. Severe, prolonged pain destroys the quality of life of those who suffer it and the need to abolish this kind of pain is urgent.

But we must first recognise another kind of pain - one that has positive aspects. Certain brief, acute pains, usually suffered after an injury or infection, have genuine survival value. These pains make us rapidly pull a hand away from a hot oven, lift a foot off a sharp object or telephone for an ambulance when we develop sudden discomfort in the abdomen or chest.

Such rapid responses to pain are aimed at preventing or minimising serious damage to the body and are important for learning to avoid future encounters with dangerous objects and situations. Heightened sensitivity to pain during healing also prevents us from reinjuring ourselves and postponing full recovery.

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People who are born without the ability to feel pain provide convincing testimony of how valuable some acute pain can be. Many of these people sustain extensive burns, bruises and lacerations in childhood, and have difficulty learning to avoid inflicting wounds on themselves.

Failure to feel pain after a ruptured appendix, which is usually accompanied by severe abdominal pain, led to near-death in one such man. Another walked on a leg with a cracked bone until it broke completely. Similarly, a woman sustained numerous burns without feeling them and her mouth was scarred from blisters as a result of drinking burning-hot liquids. Her daughter had the same condition and, aged seven, pressed her buttocks up against a grated bathroom heater after taking a bath, branding herself with five large crosshatches without feeling any pain. Such stories make it clear that we do not want to be totally free of the ability to feel acute pain. It saves lives.

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In contrast, chronic pain is destructive and has no redeeming features. One form of chronic pain is associated with unremitting diseases such as cancer and arthritis that destroy body tissue, and with various well-defined pathologies of the body's functions, such as protruding discs in the spine or insufficient blood supply to heart tissue.

Attempts to relieve these pains often work. Cancer pain, for example, can be greatly diminished by appropriate doses of morphine or other opioid drugs, often given in combination with other drugs, or even with psychological therapies, to enhance and maintain their effectiveness. Yet, despite the best efforts of hospitals, between 5 and 10 per cent of patients with cancer continue to have moderate to high levels of pain. Near the end of life, when they serve no useful purpose, these unrelenting pains make living unbearable and have been known to drive victims to suicide. Will we ever be free of them?

It is possible. New drugs are in the pipeline and, with luck, cancer pain may be whittled down by the development of specialised selective drugs or other therapies. The explosive growth of research in the field of pain in recent years has led to the discovery of two new classes of very effective analgesic drugs. These were never suspected of having this kind of power but were developed to control epilepsy and psychological depression. Anti-epilepsy drugs are usually used to control neuropathic pain, which is associated with the pathology of peripheral nerves, while antidepressants relieve several kinds of pain, even in patients who are not depressed, so that their analgesic action is separate from their effects on depression.

New drugs to relieve arthritic pain have become available, and even more powerful ones are on the way. It is possible that chronic pain associated with major definable pathology in the body may eventually yield and become pain-free zones in medicine.

Unfortunately, this optimistic outlook does not apply to the kind of chronic pain that has no well-defined cause, such as phantom limb pain.

People who have an arm or a leg amputation almost immediately feel a "phantom limb", which seems so real that they try to reach for a ringing telephone with their phantom hand.

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The reality of the phantom is especially vivid in the 60 to 70 per cent of amputees who feel terrible pain - cramping, burning, crushing - in calf, ankle, hand or other areas. The pain may be relieved briefly by local anaesthetic injections or some oral analgesic drugs. But, tragically, the cause of the pain is poorly understood and no effective treatment has yet been found.

Neurosurgeons may remove the little ball of tangled neurons (the neuroma) that form in the stump and pain may be relieved for a while, but it soon returns. Then a neurosurgeon may cut the nerve near its point of entry into the spinal cord, and later may cut part of the spinal cord, usually without prolonged relief. Sometimes electrodes are lowered into the brain to burn out parts of the thalamus or nearby areas. Even the cortex representing the missing limb may be removed.

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None of these operations has been effective long enough to be counted on as a reliable therapy. Even when a few inches of the spinal cord are removed, leaving a gap so that no information from the lower limbs can reach the brain, the pain usually persists in the same areas of the phantom body.

The reason is now at least partly clear. When sensory input to brain cells is cut off, these cells begin to fire spontaneously in abnormal bursts. The pathological patterns of nerve impulses are assumed to generate pain perception. Anti-epileptic drugs help some of these patients, but most continue to suffer. Again, new drugs are being developed, and some may work. Sadly, there are no grounds for optimism that a drug to control this unrelenting pain is imminent.

But at least these types of pain are beginning to be better understood. A striking feature of chronic pain, which includes most kinds of backache, headache, facial pains, musculoskeletal pains, pelvic and visceral pains, is that it involves activity in all of the brain. Not only are the sensory receiving and processing areas of the brain known to be active when people are in pain, but areas of the limbic system (which plays a role in emotion, motivation, suffering), and cognitive areas (which evaluate the situation, give meaning to it, foresee hope or doom) all play a role too.

Take headaches. Two of the most common forms are tension headaches and migraine (vascular) headaches. Close study shows that tension headaches are not always associated with increased tension in head and neck muscles, and migraine headaches may come and go with no clear relationship to blood pressure changes in the vascular system of the head. Also, stress plays a major role in both kinds of headache but not in a predictable way. All three factors - muscle tension, blood flow and stress - are important to varying degrees but no one alone is a reliable predictor of the type of headache or when it will come and go. That is why treating only one of these rarely seems to make a big difference for a long enough period of time. Effective treatment often involves all three.

While we have excellent new drugs for some kinds of headache and our understanding of them has advanced considerably in recent years, we cannot cure them all, and continued suffering by millions of people indicates we still have a long way to go. Yet there is still room for optimism. Now that we recognise the powerful role of the brain and all its contributions - sensory, emotional, cognitive - we have recently begun to explore the brain's mechanisms for generating consciousness and the perception of pain and suffering. Indeed, we may be at a stage in our science comparable to Copernicus's proposal in the 15th century that, contrary to common sense, the earth rotated around the sun. Later confirmation of this simple fact led, in less than 500 years, to the discovery of our solar system, then eventually to our vast, expanding universe. So too, contrary to common sense, we now know that the brain can generate pain in the absence of any evidence of injury, infection or other pathology.

The brain is extraordinarily complex with its hundred billion nerve cells and trillions of connections, but scientific progress is sure, eventually, to reveal its secrets. There is certainly the hope that those secrets will also illuminate ways to wipe out the horrible pain and suffering that afflicts people all over the world.

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Ronald Melzack is emeritus professor of pain studies at McGill University.

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