A colorful image of a human brainShare on Pinterest
Researchers say circuits in the brain could help provide pain relief without the use of opioids. Westend61/Getty Images
  • Researchers have identified an alternative pain control circuit in the brains of mice, one that can help effectively manage pain relief.
  • Targeting this circuit helped provide pain relief similar to that of opioids without the side effects.
  • Opioids are effective at managing pain, but there are many potential side effects as well as a risk of addiction, abuse, and overdose.
  • Researchers plan on expanding their findings to see if they can be replicated in human test subjects.

When it comes to relieving pain, opioids are virtually unmatched.

These drugs, which act on opioid receptors in the brain and the body, pack a potent punch and can effectively manage intense pain.

The downside is the addictive nature of opioids.

The U.S. Centers for Disease Control and Prevention (CDC) reports that the number of deaths by drug overdose increased sixfold between 1999 and 2021, with many of these deaths attributed to the ongoing opioid epidemic.

This places doctors in a tricky spot, since prescription opioids such as hydrocodone and oxycodone are powerful tools when it comes to pain management but also create the potential for addiction, abuse, and overdose.

Now, researchers from the University of Chicago say they may have found a new way to treat pain, one that can produce a similar effect to opioids without actually using the medications.

The key is an alternative pain control pathway in the brain, one that relieves pain but does not have the associated tolerance or withdrawal symptoms.

The study, which was supported by grants from the National Institutes of Health, was published today in the medical journal Neuron.

Daniel McGehee, a professor of anesthesia and critical care at the University of Chicago, was the senior author of the study. He told Medical News Today that it’s important to find alternative ways to manage pain.

“A lot of [the opioid epidemic] is being driven by prescription opioids or synthetic opioids rather than the typical heroin or morphine,” he said. “These drugs are widely available in part because of their use as pain relievers. If we can replace opioids with other analgesics, it’s going to help in reducing the possibility of people abusing them.”

McGehee said that in addition to the well-known side effects of opioids, they can create more subtle complications such as an increased tolerance, which can lead to a vicious cycle of higher dosages, reduced results, and more susceptibility to abuse.

“People who are on opioids for an extended period will actually show heightened pain when they stop the drug, so these complications would be fantastic to avoid,” he explained. “In our study, what we’ve tried to do is explore some of those same potential complications in mouse models of pain control.”

McGehee and his fellow researchers explored the brain circuitry of lab mice, focusing specifically on the neurotransmitter acetylcholine, a compound that affects brain activity and acts as mediator between nerves and muscles.

“It’s involved in all sorts of interesting behavioral and cognitive effects in the brain, but until this study, we really didn’t understand how acetylcholine is interacting with pain control systems,” he said.

The researchers found that in pain-inducing circumstances, there’s a suppression of acetylcholine, which is seemingly the opposite of what it should be doing.

“That inhibition, we believe, is contributing to a change in the threshold for a painful experience and so it’s actually sensitizing the animal to pain,” said McGehee. “It’s potentially a very important observation that has to do with not only how the background threshold is controlled, but it’s also an opportunity for intervening to recruit the receptors that are normally activated by acetylcholine and potentially reverse the painful state.”

Researchers were indeed able to reverse the painful state in mice by targeting these pathways. They reported that the pain relief provided by this reversal was robust and effective, even in mice that had developed a tolerance to opioids.

“That inhibition is basically mimicking what opioids do in the same cells, and the nicotinic receptors and opioid receptors that are controlling pain seem to be on the same set of neurons,” said McGehee. “We hope that this is an avenue towards developing drugs that can relieve pain to replace opioids and also potentially reduce their use.”

Santosh Kesari, a, neurologist at Providence Saint John’s Health Center in California and the regional medical director for the Research Clinical Institute of Providence Southern California, told Medical News Today that the data shows great promise that could someday lead to better ways of managing pain without opioids.

“This is an exciting study opening up a new approach to pain management,” explained Kesari, who was not involved in the study. “The authors found that modulating the acetylcholine receptor produced an analgesic effect uniquely from the way opioids work and did not induce tolerance. This non-opioid pathway could open the door to future development of drugs for pain control, and reduce the need for opioid medications and complications related to chronic opioid use.”

While the research offers intriguing implications, it’s worth noting that only mice were studied.

This data is helpful and could be replicated in human subjects – but that research will need to take place in order to see if the findings carry over, researchers acknowledged.

To that end, McGehee says that he and his colleagues would be interested in partnering with a drug company to test compounds that target this receptor system and test whether or not it has analgesic effects.

“The other longer-term opportunity that we’re interested in pursuing is to look closer at the control points for this whole acetylcholine release in the system,” he said. “The question is, are there receptors or mechanisms that we can target in those cells to achieve pain relief?”