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A new study in Nature Communications suggests that a compound that reduces the severity of a pain “flashback” in animal models might have potential for improving pain relief.

Flashbacks (also called aversive experiences) are events that occur when an animal is subjected to an unusual or painful stimulus prior to experiencing the pain itself. In many animals, a flashback would occur within 1–3 days after initial pain, with a time course that is comparable to when humans experience a pain flashback.

In addition to animals, we also know of examples of patients with epilepsy who have a severe pain “flashback” for days after receiving a dose of m-dopamine, an antidepressant drug that acts on NMDA receptors in the brain.

“Our study is at the cutting edge of understanding how a long-term drug-induced neuroadaptive deficit can be reversed by exposure to the ‘normal’ ‘painless’ memory,” says first author Michael Cai of Washington University, St. Louis. In previous studies, Cai, an associate postdoctoral fellow, examined a molecule called SERT, or serotonergic transmitter receptor, that is linked to the experience of pain.
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The next step, Cai says, is to develop drugs that target NMDA receptors in the same manner as the SERT. But because NMDA receptors are also known to influence memory, other researchers have suggested that an antidepressant could work by selectively “short-circuiting” NMDA receptor activity. Such drugs are on the horizon for pain relief.

A team led by Robert Stolz of Yale University, New Haven, is also exploring this idea. When subjects see a visual flash, scientists know that they have a brief memory of the stimulus and when they go through a process called “reorganization,” the memories of the stimulus fade away. Scientists know, however, that re-organization does not occur completely, and that memory can be strengthened, sometimes even after re-exposure.

“Re-exposure to some stimuli does not guarantee re-organization of an individual’s memory of