Brainstem blocks pain to protect key behaviors


Certain behaviors, such as eating, drinking and urinating, are so crucial to survival that the brains of all vertebrates contain clusters of nerve cells that can suppress pain long enough to allow the animal to eat, drink.

A report from researchers at the University of Chicago, published in the Proceedings of the National Academy of Sciences ( PNAS ), shows that by activating "OFF" cells and shutting down "ON" cells in the ventromedial medulla ( VMM ) – a small region in the brain stem – animals provide themselves with a form of "eating-induced analgesia," allowing them to complete essential tasks even in a difficult situation.

" Escaping pain and potential dangers may be important protective behaviors, but eating, drinking, and eliminating wastes are absolutely essential," said study author Peggy Mason, at the University of Chicago. " What we found was a very effective system that lets these animals focus on the essentials and postpone concerns that are slightly less pressing. It's as if they could give themselves a six-second dose of morphine, allowing hunger to override pain."

Mason and colleague Hayley Foo studied adult male rats in containers with a wire mesh floor that enabled them to deliver radiant heat to one hind paw. The heat caused no damage but was annoying enough to make the animal withdraw that paw within seconds.

When the rats ate, however, they postponed retracting the heated paw for six to eight seconds and continued to eat.

Food choice made no difference. Rats focused just as intently on standard rat chow as when munching chocolate chips, yogurt drops or butter cookies.

Although earlier studies found that eating took precedence over pain in food-deprived animals, this is the first study to show that feeding suppressed pain in well-fed animals.

To understand the neural basis of this form of pain suppression, the researchers next inserted electrodes to monitor brain activity in feeding rats.

The suspected source of pain relief was a cluster of cells in the VMM.

In 1979, Howard Fields of the University of California at San Francisco identified two groups of neurons in the brain stem that could enhance or inhibit pain. Neurons that "facilitate" pain, which he labeled "ON cells, fire in bursts when animals are awake and are inactive during slow-wave sleep. "OFF" cells, which suppress pain, are active during slow-wave sleep.

Foo and Mason found that the pain-enhancing ON cells were inhibited and the pain-suppressing OFF cells were excited during feeding, results that duplicated the effects of Morphine.
The changes occurred only during selected portions of eating, while the animal was both holding and chewing the food. A similar response took place when the animals drank water or urinated.

This response "protects critical behaviors from disruption," the authors note, "allowing an animal to nourish itself without being distracted."

As a final test the authors used drugs to inactivate the VMM. This completely eliminated the delayed response to pain.

" This is the best evidence so far on the biological significance of OFF cell activity," said UCSF's Fields, who was not connected with the study. " It is a major step in understanding the neurobiological mechanisms of decision making in the face of conflict -- in this case the choice between whether to feed or flee. Off cells help you feed instead of flee."

Mason and Foo also found, however, that in situations that might be more dangerous, the feed-or-flee balance could be tipped the other way. Given just before feeding, a strong puff of air – perhaps indicating a nearby predator -- activated ON cells, and restored pain sensation. Such "predation-related stimuli," the authors speculate, "activate ON cells and thereby evoke a state of vigilant eating without concurrent sensory suppression."

Source: University of Chicago Medical Center, 2005


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