Graphic image of neurons lighting up on a purplish background.

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Stanford Medicine Scope - February 13th, 2017 - by Tracie White

Everyone loves endorphins — those naturally occurring chemicals in the body that are commonly credited with the euphoric highs caused by running or sex or even hot peppers.

But there’s another compound — a cousin to the endorphin — that deserves similar accolades. Enkephalins are peptides that are produced in response to certain stimuli — such as stress, fear or pain — that also have potent painkilling properties.

In a Stanford study published recently in Neuron, researchers identify a neural circuit in the brain that helps explain how the body uses these painkillers. This circuit can reduce or increase pain thresholds, by either increasing or decreasing the level of enkephalins released in response to a particular stimuli.

“We propose that this system could underlie the increase in pain caused by stress and anxiety, and the decrease in pain caused by positive expectations, the placebo effect, and meditation,” said Gregory Scherrer, PhD, Pharm.D., senior author of the study and assistant professor of anesthesiology, perioperative and pain medicine and of neurosurgery. “This is also useful because it could be targeted to make new pain medications.”

The authors write that this “pain-stress” loop might even contribute to the sensation of pain in patients with psychiatric disorders or underlie pain catastrophizing, which is characterized by exaggerating the severity of pain and ruminating on it.

In the 1970s, scientists discovered cells in the brainstem that can both increase and decrease pain, Scherrer said. And it’s been known there are neurons in the brain that can alter the transmission of pain signals via the spinal cord, a process known as descending pain control. But it hasn’t been shown exactly how this system works.

To explore this, the researchers first determined the source of enkephalins using mice. They then took a version of the rabies virus that could only infect the neurons that produce enkephalins to find out how these neurons are connected to the rest of the brain. What they saw was that the neurons that produce the painkilling chemicals were connected to only one place within the brainstem known to be important for descending pain control.

Further results showed the cells in the brainstem that release these enkephalins have the ability to either increase or decrease the amount released depending on what stimulates the pain circuit. Researchers surmise that stress activates the circuit so that there are fewer pain relievers released, while meditation or other positive influences inhibit the circuit so that more enkephalins are released.

“This is important because this descending pain system, which works through the spinal cord to trigger neurotransmitters, is involved in the placebo response and meditation,” Scherrer says. “Or when you’re hungry or not sleeping, or in a bad mood or stressed — all this can affect this system of descending pain control.”

Scherrer added the results of the study were unexpected because they are counterintuitive.

“If you activate this circuit, which we have discovered facilitates pain, it uses the inhibition of a pain inhibitor to cause pain,” Scherrer says. “It works by inhibition of inhibition. We don’t know why. It is surprising.”

Originally published at Stanford Medicine Scope Blog