Chronic Pain: Hope Through Research

Interestingly, a pair of Canadian and English investigators speculated that such pain-suppressing pathways must exist when they devised a new "gate theory of pain" in the midsixties. Their idea was that when pain signals first reach the nervous system they excite activity in a group of small neurons that form a kind of pain "pool." When the total activity of these neurons reaches a certain minimal level, a hypothetical "gate" opens up that allows the pain signals to be sent to higher brain centers. But nearby neurons in contact with the pain cells can suppress activity in the pain pool so that the gate stays closed. The gate-closing cells include large neurons that are stimulated by nonpainful touching or pressing of your skin. The gate could also be closed from above, by brain cells activating a descending pathway to block pain.

The theory explained such everyday behavior as scratching a scab, or rubbing a sprained ankle: the scratching and rubbing excite just those nerve cells sensitive to touch and pressure that can suppress the pain pool cells. The scientists conjectured that brain-based pain control systems were activated when people behaved heroically -- ignoring pain to finish a football game, or to help a more severely wounded soldier on the battlefield.

The gate theory aroused both interest and controversy when it was first announced. Most importantly, it stimulated research to find the conjectured pathways and mechanisms. Pain studies got an added boost when investigators made the surprising discovery that the brain itself produces chemicals that can control pain.

The landmark discovery of the pain-suppressing chemicals came about because scientists in Aberdeen, Scotland, and at the Johns Hopkins University Hospital in Baltimore were curious about how morphine and other opium-derived painkillers, or analgesics, work.

For some time neuroscientists had known that chemicals were important in conducting nerve signals (small bursts of electric current) from cell to cell. In order for the signal from one cell to reach the next in line, the first cell secretes a chemical "neurotransmitter" from the tip of a long fiber that extends from the cell body. The transmitter molecules cross the gap separating the two cells and attach to special receptor sites on the neighboring cell surface. Some neurotransmitters excite the second cell -- allowing it to generate an electrical signal. Others inhibit the second cell -- preventing it from generating a signal.

When investigators in Scotland and at Johns Hopkins injected morphine into experimental animals, they found that the morphine molecules fitted snugly into receptors on certain brain and spinal cord neurons. Why, the scientists wondered, should the human brain -- the product of millions of years of evolution -- come equipped with receptors for a man-made drug? Perhaps there were naturally occurring brain chemicals that behaved exactly like morphine.

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