New Study Observes the Body's Natural Painkillers in Action

Zubieta JK et al., Regional mu opioid receptor regulation of sensory and affective
dimension of pain, Science, 2001; 293(5528):311-5.

A new study offers insight into the way the human body dampens pain, by producing and wielding natural opioids such as endorphins and enkephalins. The study found that a 20-minute episode of jaw muscle pain caused a surge of the production of natural painkillers and a distinctive pattern of activity at opioid receptor sites around the brain. Revealingly, the ability to suppress pain appeared to vary substantially from subject to subject.
In a cross-over study, Jon-Kar Zubieta, MD, et al. randomly allocated a group of volunteers to one of two interventions: (1) salt water that caused 20 minutes of pain; (2) the remaining subjects received a placebo injection that did not stimulate pain. Through a variety of means, including positron emission tomography (PET) scanning, Zubieta et al. studied production of endogenous opioids and activity at mu opioid receptors around the brain. They correlated the brain activity to the subjects' pain experiences.

The study demonstrated that the painful stimulus caused the most notable opioid activity in regions of the brain associated with sensation and emotion.

"We saw an intense activation of the mu opioid system in areas such as the amygdala, the thalamus, the hypothalamus, the frontal cortex, and the nucleus accumbens, as much as a 12% changed over baseline conditions," says Zubieta. "And the higher the level of activation, the lower the scores the volunteers gave for pain-related sensations like feeling feelings of the unpleasantness of pain."

The pain, in other words, caused the body to produce a burst of natural opioid receptors, and apparently short-circuited pain-producing or nociceptive reactions.

The experimental subjects demonstrated great individual variability in their response to pain, though all had a pain stimulus of similar intensity. And the response correlated with activation of the mu opioid system.

"This may help explain why some people are more sensitive, or less sensitive, than others when it comes to painful sensations," Zubieta says. "We show that people vary both in the number of receptors that they have for these anti-pain brain chemicals, and in their ability to release the anti-pain chemicals themselves. Both of these factors appear to determine the emotional and sensory aspects of a painful experience. Such variability in the pain-response system may help explain why some people react to pain and pain medications differently." It may also help explain, according to Zubieta, why some people develop chronic pain conditions, and others don't.

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