A newly announced grant from the MS Society is helping researchers at the University of Alberta to better understand the underlying cause of chronic pain that afflicts an estimated half of people with multiple sclerosis, and how to eradicate it.
Bradley Kerr and his team are looking in particular at the peripheral nervous system, which involves all the nerves in the body outside of the brain and spinal cord. The researchers will use the funding, worth just under $300,000 over three years, to study one of the most common types of chronic neuropathic pain in MS, trigeminal neuralgia—a facial pain that can be devastating for sufferers.
Chronic neuropathic pain occurs when the nervous system has suffered an injury or is being affected by a disease. It can be especially difficult for sufferers because many conventional pain-relieving therapies are ineffective—which is why understanding the underlying cause is key to treating the pain, according to Kerr.
Kerr said his interest in this research area arose because he felt there was a knowledge gap that needed addressing. For a long time, he noted, the focus in MS research was on the central nervous system, on things such as the destruction of the myelin sheath (the insulation around the nerves that is eroded in MS patients). And while patients were coming to clinicians with complaints of pain, researchers weren’t digging deeper into the cause.
“It was never really on the forefront of anyone’s thinking about the disease,” said Kerr. “Very few people were asking questions about pain and sensory function.”
Kerr and his team turned their attention to the dorsal root ganglion, a cluster of nerves within the parasympathetic nervous system. “They’re the neurons outside of your spinal cord that are listening to the outside world; they’re sensing things on the body and initially transmitting that first signal to the spinal cord, and up to the brain,” said Kerr.
“We think that there is actually a problem at that initiating level.”
Kerr has discovered that microRNA-21, a type of molecule located in the dorsal root ganglion that is essential in the regulation and expression of genes, is abundant in people with MS. This microRNA is unique in that it has the ability to bind to certain receptors in a similar way to neurotransmitters, which are responsible for sending messages—including transmitting pain—from nerve cells to other parts of the body. The receptors that microRNA-21 binds to are also found in much higher volumes in MS patients, particularly in women with the disease.
Kerr hypothesizes that this pathway amplifies pain signals and inflammation in the body, and the fact that these molecules are even more abundant in women fits with data showing that women report more of this particular type of chronic pain. Kerr’s research in this area has been aided by doctoral student Timo Friedman, who was integral to identifying the pathway the team is currently exploring, and graduate student Olivia La Caprera, who is responsible for many of the behavioural studies involved in the project.
The existing belief, explained Kerr, was that while MS affects the central nervous system, the cells within the peripheral nervous system were likely normal—but that isn’t the case.
“What we found is that those peripheral neurons are also affected, and these neurons are basically the starting point of pain.”
Kerr said he hopes if his lab confirms that the interaction between microRNA-21 and the receptors is what provokes neuropathic pain, they will be able to collaborate with other researchers to create a drug that targets this pathway. In terms of drug discovery, it is far easier to target the peripheral nervous system than the central nervous system, because safely administering drugs to the brain and spinal cord can be challenging and comes with many side-effects.
“If we obtain clear results from this study, we’ll be able to develop treatments for pain that will be easier to translate into patient care,” said Kerr.