Further evidence that endorphins figure importantly in pain control comes from a new look at some of the oldest and newest pain treatments. The new look frequently involves the use of a drug that prevents endorphins and morphine from working. Injections of this drug, naloxone, can result in a return of pain which had been relieved by morphine and certain other treatments. But, interestingly, some pain treatments are not affected by naloxone: Their success in controlling pain apparently does not depend on endorphins. Thus nature has provided us with more than one means of achieving pain relief.
Those same investigators note that naloxone injections can block pain relief produced by acupuncture. Others have not been able to repeat those findings. Skeptics also cite long-term studies of chronic pain patients that showed no lasting benefit from acupuncture treatments. Current opinion is that more controlled trials are needed to define which pain conditions might be helped by acupuncture and which patients are most likely to benefit.
Now experiments suggest that the placebo effect may be neurochemical, and that people who respond to a placebo for pain relief -- a remarkably consistent 35 percent in any experiment using placebos -- are able to tap into their brains' endorphin systems. To evaluate it, two NINDS- and NIDR-supported investigators at the University of California at San Francisco designed an ingenious experiment. They asked adults scheduled for wisdom teeth removal to volunteer in a pain experiment. Following surgery, some patients were given morphine, some naloxone, and some a placebo. As expected, about a third of those given the placebo reported pain relief. The investigators then gave these people naloxone. All reported a return of pain.
How people who benefit from placebos gain access to pain control systems in the brain is not known. Scientists cannot even predict whether someone who responds to a placebo in one situation will respond in another. The San Francisco investigators suspect that stress may be a factor. Patients who are very anxious or under stress are more likely to react to a placebo for pain than those who are more calm, cool, and collected. But dental surgery itself may be sufficiently stressful to trigger the release of endorphins -- with or without the effects of placebo. For that reason, many specialists believe further studies are indicated to analyze the placebo effect.
As research continues to reveal the role of endorphins in the brain, neuroscientists have been able to draw more detailed brain maps of the areas and pathways important in pain perception and control. They have even found new members of the endorphin family: Dynorphin, the newest endorphin, is reported to be 10 times more potent a painkiller than morphine.
At the same time, clinical investigators have tested chronic pain patients and found that they often have lower-than-normal levels of endorphins in their spinal fluid. If you could just boost their stores with man-made endorphins, perhaps the problems of chronic pain patients could be solved.
Not so easy. Some endorphins are quickly broken down after release from nerve cells. Other endorphins are longer lasting, but there are problems in manufacturing the compounds in quantity and getting them into the right places in the brain or spinal cord. In a few promising studies, clinical investigators have injected an endorphin called beta-endorphin under the membranes surrounding the spinal cord. Patients reported excellent pain relief lasting for many hours. Morphine compounds injected in the same area are similarly effective in producing long-lasting pain relief.
But spinal cord injections or other techniques designed to raise the level of endorphins circulating in the brain require surgery and hospitalization. And even if less,drastic means of getting endorphins into the nervous system could be found, they are probably not the ideal answer to chronic pain. Endorphins are also involved in other nervous system activities such as controlling blood flow. Increasing the amount of endorphins might have undesirable effects on these other body activities. Endorphins also appear to share with morphine a potential for addiction or tolerance.
Meanwhile, chemists are synthesizing new analgesics and discovering painkilling virtues in drugs not normally prescribed for pain. Much of the drug research is aimed at developing nonnarcotic painkillers. The motivation for the research is not only to avoid introducing potentially addictive drugs on the market, but is based on the observation that narcotic drugs are simply not effective in treating a variety of chronic pain conditions. Developments in nondrug treatments are also progressing, ranging from new surgical techniques to physical and psychological therapies like exercise, hypnosis, and biofeedback.