Stress may upend opioid pain relief in IBD

Last Updated: 2016-10-26

By David Douglas

NEW YORK (Reuters Health) - The psychological stress that accompanies chronic conditions such as inflammatory bowel disease (IBD) may reverse the analgesic action of both endogenous opioids and opioid medication, according to in vitro and murine studies.

As Dr. Stephen J. Vanner told Reuters Health by email, "Psychological stress can switch opioid signaling in pain sensing neurons that results in opioid drugs causing pain rather than relieving it."

In a September 27 online paper in Gut, Dr. Vanner of Kingston General Hospital, Ontario, and colleagues note that as IBD evolves, peripheral nociceptive signaling reflects a balance of pronociceptive and antinociceptive mediators signaling to dorsal root ganglia (DRG) neurons.

"In the transition from acute to chronic inflammation," they add, "the expansion of the endogenous opioid system causes an important shift in this balance."

In a series of experiments involving inflamed colon from patients with ulcerative colitis (UC) and mice with dextran sodium sulfate-induced chronic colitis, the team examined such changes in the excitability of colonic DRG nociceptors.

Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing the mice to water avoidance stress.

The researchers found that "stress inhibits the antinociceptive action of endogenous opioids and, paradoxically, endogenous opioid signaling is switched, resulting in an apparent pronociceptive effect on neuron excitability."

This can involve two different pathways, one acting directly by signaling to DRG neurons to alter intracellular signaling, and the other indirectly by suppressing endogenous opioid production/secretion and reactivation of acute inflammation.

Such circumstances, they add, "could lead to increasing pain and result in escalating doses of opioid analgesics in patients with IBD."

"Our study," the investigators conclude, "identifies a number of potential therapeutic targets, both pharmacological and psychological, that could be examined to help prevent the use of high doses of opioids."

SOURCE: http://bit.ly/2eM5YSs

Gut 2016.