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 benefits from
acupuncture treatment. 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 brain's 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 placebo 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 area 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.
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.
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