NOVEMBER 13, 2023
Data from a recently published study indicate that pharmacologically boosting acetylcholine in mice’s brains provokes an analgesic response, even in subjects that were opioid tolerant.
Roughly 20% of adults in the United States have chronic pain, according to the CDC. The deleterious effects of opioids, on both patients and communities, mean those suffering from chronic pain desperately need new pain medications that do not pose the risk for dependence.
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Data from a recently published study indicate that pharmacologically boosting acetylcholine in mice’s brains provokes an analgesic response, even in subjects that were opioid tolerant.
Roughly 20% of adults in the United States have chronic pain, according to the CDC. The deleterious effects of opioids, on both patients and communities, mean those suffering from chronic pain desperately need new pain medications that do not pose the risk for dependence.
“Our results indicate that acetylcholine and its receptors may provide novel targets for treating chronic pain that don’t have the side effects or abuse potential of opioid drugs,” study author Daniel S. McGehee, PhD, an associate professor of anesthesia and critical care at the University of Chicago, told Pain Medicine News.
According to researchers, previous studies established that targeting an acetylcholine receptor called alpha-7—located in the ventrolateral periaqueductal gray area of the brain—produced an analgesic effect.
The researchers’ current study demonstrated that boosting acetylcholine in opioid-tolerant mice still gave these subjects an analgesic effect (Neuron 2023;111[21]:3414-3434.e15. doi:10.1016/j.neuron.2023.08.017). These results point to the fact that the acetylcholine receptor is part of a different neural pathway from those that opioids use, meaning opioid tolerance likely does not dampen acetylcholine’s effects. Importantly, the mice did not show signs of drug dependence.
Furthermore, in the absence of pain, mice did not show a preference for environments where they received the drug that stimulated acetylcholine. This finding led the investigators to believe the acetylcholine stimulation is not habit forming.
McGehee cautioned that “rodent models provide great insight into nervous system function; and while the neural circuitry involved is similar to humans, it is not the same.”
He also indicated that future studies would examine the analgesic effects of manipulating the ventrolateral periaqueductal gray area of the human brain with acetylcholine stimulation in clinical trials, but noted that there will be continuing study of acetylcholine signaling in mice.
“This may lead to even better pain treatments,” McGehee concluded.
—Myles Starr
McGehee reported no relevant financial disclosures.
