Endogenous cannabinoids play a crucial and unsuspected role in the phenomenon of stress-induced analgesia, researchers report in Nature this week.

Researchers have known that stress-induced analgesia involves two mechanisms: a well-characterized opioid pathway, and a mysterious nonopioid pathway, lead author Andrea Hohmann of the University of Georgia told The Scientist. In their latest work, Hohmann and colleagues established that the second pathway is mediated via the lipids 2-arachidonoylglycerol (2-AG) and anandamide, which bind cannabinoid CB1 receptors in the periaqueductal gray region in the midbrain.

"It all started with an interest in examining the natural conditions that would activate the release of the body's own marijuana-like compounds," said Hohmann. The researchers examined whether the phenomenon could be mediated by cannabinoids, because those molecules are known to suppress pain by inhibiting pain-sensitive neurons.

To quantify stress-induced analgesia and to measure basal nociceptive thresholds, they delivered brief electric foot shocks to...

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