The pain relievers

Imagine the sensation you feel when your fingers go numb in the cold. What starts off as a small tingle becomes increasingly painful until eventually you lose feeling in your fingertips. Now, imagine living with that chronic pain and numbness every day. These are the early symptoms of peripheral neuropathy, a condition that results from damage to the nerves, impairing their ability to send messages from the brain and spinal cord to the muscles, skin, and other areas of the body.

“It begins in the small fibers of your nerves. The first nerves to be damaged are farthest away from the spinal cord, starting in your fingers and toes,” says Dr. Aaron Michelfelder, chair of Family Medicine at Loyola University Chicago’s Stritch School of Medicine. “It’s like someone is holding hot coals under your feet, and at the same time feeling cold, like your toes or fingers are burning. It’s a strange sensation.”

Diagnosed with peripheral neuropathy six years ago, Michelfelder has a personal understanding of chronic nerve pain. “It really impacts life when it comes to sleep,” he explains. “Your feet tend to hurt the worst at night after you’ve walked on them all day. You lie down to go to sleep, put them up, and then they start to burn.”

In addition to managing his own condition, Michelfelder treats patients with peripheral neuropathy at his acupuncture practice in Maywood, Illinois. Inserting needles into the body’s pressure points can stimulate blood flow and potentially restore damaged nerves. While acupuncture has been successful relieving pain for some patients, for many it’s only a short-term fix, not a cure.

However, another Loyolan may have discovered a potential and promising treatment for this painful condition. Just a few buildings away from Michelfelder’s classroom on the Health Sciences Campus, Virginie Mansuy-Aubert, an associate professor of cell and molecular physiology at Stritch, is conducting research into the microbiome—the trillions of bacteria, fungi, and viruses colonizing our digestive tract—and its relationship to nerve pain. “We know that our gut impacts our brain and our nervous system; what we don’t know is how or why,” she says.

In Fall 2020, her lab published a study in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) that identified a potential link between the gut microbiome and nerve pain. While past research has shown a link exists between the microbiome and brain, Mansuy-Aubert’s study is the first to specifically show that the composition of the microbiome can impact nerve pain associated with obesity.

The gut microbiome is heavily influenced by nutrition and other things we ingest throughout our lifetime.

According to Mansuy-Aubert’s study, higher levels of butyrate, a short-chain fatty acid produced in the gut, may be associated with pain improvement and neuron regeneration. “Our study suggests that the microbiome of obese people is associated with neuronal changes” says Mansuy-Aubert. “It is likely that if we change the composition of the microbiota, we may be able to reduce diabetic-related diseases such as peripheral neuropathy and associated complications.”

Out of the estimated 30 million people in the United States who suffer from peripheral neuropathy, more than 60 percent have diabetes, according to the Foundation of Peripheral Neuropathy. And out of the 34.2 million Americans have diabetes, 50 to 60 percent have diabetes-related peripheral neuropathy (DPN). The prevalence of peripheral neuropathy in people with diabetes is due to high blood sugar, which can injure nerves throughout the body, causing symptoms ranging from numbness to mild or even severe pain and, in some extreme cases, require amputation.

To manage the pain, it’s common for physicians to prescribe opioids, even though clinical guidelines do not recommend them as a treatment. “We need to focus on alternative pain treatments that don’t rely on opioids– options that are safe, not addictive, and get to the root cause of the problem,” says Lara Dugas, associate professor of public health sciences at Loyola’s Parkinson School of Health Sciences and Public Health.

Dugas co-authored the PNAS study and is leading two international, NIH-funded studies examining the association between the gut microbiota and the development of diabetes in people of African descent. As someone who sees patients suffering from diabetic pain on a regular basis, she understands just how powerful this kind of breakthrough could be. “Our work may offer more treatment options. Getting people off opioids is so important,” says Dugas. “If we have a metabolite like butyrate that’s associated with better health outcomes, then there are ways we can change the microbiome to be healthier.”

Since a known way to increase butyrate is through diets rich in dietary fiber, experts like Dugas are exploring the role nutrition may play in decreasing pain. In the meantime, Mansuy-Aubert’s lab will continue to study butyrate at a molecular level and explore the potential of a drug discovery study. “Our study has really laid the groundwork for other researchers at Loyola and beyond,” says Raiza Bonomo, first author on the PNAS study and a Loyola doctoral student in cell and molecular physiology. “Many people are beginning or advancing their studies because of this research.”

With more studies comes more hope for finding novel and effective treatments for people living with peripheral neuropathy. “Diet is implicated in so many other conditions linked to peripheral neuropathy, like diabetes and thyroid issues,” says Michelfelder. “If we can show a correlation between the microbiome and peripheral neuropathy, that would be an incredible discovery.”

Read more stories from the Stritch School of Medicine.