Scientists have long known that injured athletes or even gunshot victims have a period of time in which the body's pain reaction is delayed. This effect is called "stress-induced analgesia." By the mid-1990s, researchers had targeted the sites of action of the brain's naturally occurring marijuana-like compounds as having a crucial role in blocking pain, but no one understood the conditions in which these compounds were released to block pain.
Researchers along the way found out there are two kinds of stress-induced analgesia mechanisms, opioid and nonopioid (or "opioid independent"). Hohmann and colleagues discovered that the opioid-independent form was produced by release of the brain's own marijuana-like compounds.
"We showed that cannabinoid receptors were involved in this remarkable phenomenon," said Hohmann, "because blocking the receptors where marijuana acts virtually erased this opioid-independent form of stress analgesia."
If this is true, was there a compound that could also prolong the action of these compounds, making them work better? The answer lay in Piomelli's pioneering work on inhibitors that break down the brain's own marijuana-like compounds.
"If we design chemicals that tweak the levels of these transmitter substances in the brain," said Piomelli, "we might be able to boost their normal effects."
When rats used in Hohmann's study were given the compound developed by Piomelli and his collaborators at the University of Urbino Carlo Bo and the University of Parma, it increased stress-induced analgesia dramatically, proving the connection between pain suppression and the release of these marijuana-like compounds.