Unlocking Pain's Secrets

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debated among the ancient Greeks, until philosophers like Democritus and Plato concluded correctly that the pain-perception center is the brain. Greek scientists found support for this theory by discovering that the brain is connected to a network of two types of nerve fibers, one set controlling motion, the other, sensation. This knowledge was lost in the Middle Ages, and superstition again took hold. Only when taboos against dissection were lifted during the Renaissance did thinkers like Leonardo da Vinci once again understand pain in terms of the nervous system.

Most refinements of this understanding have come about in the past 20 years. Today scientists have a fair idea of what happens physiologically when, for example, the big toe collides with a large, solid object. Not surprisingly, the pain message originates at the point of contact (see diagram). It begins with the release of a number of potent chemicals that are normally stored in or near nerve endings for use on just such clumsy occasions. Among these chemicals are the mysterious substance P (for pain), prostaglandins and bradykinin, probably the most painful substance known to man—just a tiny amount inserted under the skin with a needle causes excruciating pain. These substances sensitize the nerve endings and help transmit the pain message from the injured region toward the brain. Prostaglandins also increase circulation to the damaged area, causing the swelling and redness known as inflammation. The purpose of this is to attract infection-fighting blood cells that will ward off any invading bacteria. Since the days of Hippocrates, doctors have been relieving pain with salicylic acid, a precursor to aspirin that was derived from willow bark, but only in the past 15 years have they understood that it works by inhibiting the production of prostaglandins. Tylenol (the most common brand of acetaminophen) works much the same way, as do popular prescription analgesics like Clinoril (sulindac), Motrin (ibuprofen) and Dolobid (diflunisal), often used to relieve arthritis and severe menstrual cramps.

The pain signal from the stubbing of the toe travels as an electrochemical impulse along the length of the nerve to the dorsal horn of the spinal cord, a region that runs the length of the spine and receives signals from all over the body. In a tall person, the distance from toe to dorsal horn may be more than one meter, and it can take about two seconds for the message to arrive. From there, it is relayed in a bewildering flurry of chemical messages to the brain, first to the thalamus, where sensations like heat, cold, pain and touch first become conscious. Then on to the cerebral cortex, where the intensity and location of pain are recognized. This final stretch of the pathway is the great terra incognita in pain research. Says Fields:

"We can't put an electrode into the consciousness." In any case, it is the cortex that coordinates such highly sophisticated responses to pain as screaming "Ouch!" and rubbing the sore toe.

Toe rubbing, it seems, has its purpose, and one can get considerable relief by massaging or patting a sore area, just as one can relieve itching by scratching or slapping. In 1965 two researchers, Patrick Wall and Ronald Melzack, devised a brilliant theory to explain this effect: the gate-control theory of pain. According to them, only a limited amount of