SEPTEMBER 29, 2023
The ventrolateral periaqueductal gray region of the brain (vlPAG) may contain targets for pain management therapies, according to new findings. Researchers recorded an analgesic effect when the acetylcholine receptor alpha-7 was stimulated in the vIPAG of mice. This observation may lead to novel therapies, even in patients who are opioid tolerant.
“Targeting these receptors with pharmacology relieves pain in a persistent way, and pain relief is not associated with addictive effects
The ventrolateral periaqueductal gray region of the brain (vlPAG) may contain targets for pain management therapies, according to new findings. Researchers recorded an analgesic effect when the acetylcholine receptor alpha-7 was stimulated in the vIPAG of mice. This observation may lead to novel therapies, even in patients who are opioid tolerant.
“Targeting these receptors with pharmacology relieves pain in a persistent way, and pain relief is not associated with addictive effects or tolerance,” senior study author Daniel McGehee, PhD, a professor of anesthesia and critical care at the University of Chicago, told Pain Medicine News.
“If we treat mice repeatedly with opioids to induce tolerance, the cholinergic analgesia described above remains intact. Overall, targeting this system may provide robust pain relief to replace and reduce opioid use,” McGehee continued.
The researchers expected that when a drug was used to stimulate alpha7 receptors in mice, their nervous systems would be excited, and more acetylcholine would be released. Initial excitement occurred, but a state of prolonged rest and an hours-long analgesic effect ensued (Neuron 2023;S0896-6273[23]00627-X. doi:10.1016/j.neuron.2023.08.017).
Although this study was conducted in animals, human studies of other acetylcholine receptor treatments (in unrelated clinical end points, namely schizophrenia) have shown alpha7 stimulation to be safe. The next step in exploring acetylcholine receptor therapy as a pain management treatment in people is moving to a human trial of alpha7 stimulation with the specific goal of ascertaining its benefits as an analgesic.
“We hope to partner with a drug company and the National Institutes of Health to move into human testing,” McGehee said. “We are also testing how this system is controlled during painful conditions, which may help us identify other targets for recruiting this system to relieve pain.”
—Myles Starr
McGehee reported no relevant financial disclosures.
