microscopic view of EGFR receptor

UTM researcher identifies potential way to reduce chronic pain

Nicolle Wahl

By identifying a molecule responsible for activating the body’s pain receptors, Professor Loren Martin of the University of Toronto Mississauga offers hope to the one-in-five Canadians reportedly suffering from chronic pain – and other sufferers worldwide.

Martin, a behavioural neuroscientist working in collaboration with colleagues from McGill University and the University of North Carolina, has determined that inhibiting one of the body’s proteins, known as epidermal growth factor receptor (EGFR), lessens the pain associated with nerve injury and inflammation in mice. Moreover, EGFR genetic mutations were also linked to the development of head and jaw pain in people. Their research appears in the Journal of Clinical Investigation this month.

“The association of this receptor with small-cell lung cancer is well known, but we demonstrate that inhibition of this receptor is not unique to those suffering from cancer,” Martin said. “Instead, this receptor appears to be associated with general pain processing.”

The researchers further demonstrate that one particular molecule, epiregulin, is implicated in EGFR-related chronic pain.

“The EGFR receptor is activated by a well-known, much-studied family of molecules that play an important role in cell growth and proliferation,” he said, “but turns out that only one molecule in the family, epiregulin, is important in this instance. The others don’t have an impact on pain.”

These findings are extremely valuable and timely because of the prevalence of chronic pain and limited therapeutic strategies. The current options for chronic pain relief are limited to opioids, which carry the possibility of addiction, overdoses and unpleasant side effects.

Martin first became interested in pursuing this line of inquiry when he noted that cancer patients who were prescribed EGFR-inhibiting drugs reported a lessening of pain after taking the medication. A study done by his collaborators analyzed about 3,000 people and discovered that those who developed a particular type of chronic facial pain had a mutation in the EGFR receptor and in the gene coding for epiregulin. In the current study, an analysis of three human pain cohorts linked the epiregulin/EGFR pathway to chronic pain; in sampling the participants’ blood, the researchers realized that those who had chronic pain had higher than normal levels of epiregulin.

Martin then replicated those results in mice by inducing conditions that are accompanied by chronic pain and measuring the epiregulin levels in their blood.

“When we blocked the EGFR receptor with the inhibitors currently available, it reversed chronic pain in mice,” he said.

Martin and his colleagues plan to explore the therapeutic potential of controlling epiregulin, since simply inhibiting the EGFR receptor has side effects of its own that may cause reluctance to use drugs that rely on this approach.

“By normalizing the body’s levels of epiregulin, we may be able to reduce sensitivity to pain and improve the quality of life for chronic pain sufferers,” Martin said.

Contact:
Loren Martin
Assistant Professor of Psychology, UTM
Canada Research Chair in Translational Pain Research
Office: 905-569-5784
Lab: 905-828-3785
lj.martin@utoronto.ca
http://www.utmpainlab.ca/

Nicolle Wahl
Associate Director, Communications
905-569-4656
nicolle.wahl@utoronto.ca