Easing chronic pain

How Lawson researchers are advancing our understanding of neuropathic pain

When Judy Williams slipped on a patch of ice and broke her wrist six years ago, she could not imagine the health journey she was embarking on. The months that followed were sleepless ones. Judy was in excruciating pain, her hand swelled and her fingers turned blue.

She visited the emergency department four times to have her cast removed and reapplied. Judy was eventually referred to the Hand and Upper Limb Centre (HULC) at St. Joseph’s Health Care London (St. Joseph’s). Dr. Robert Richards, a plastics and microvascular surgeon, realized her injury was not a simple break and that she had complex regional pain syndrome (CRPS). Dr. Richards referred Judy to St. Joseph’s Pain Management Clinic where Dr. Collin Clarke, a Lawson scientist and an anaesthesiologist, confirmed her diagnosis.

CRPS is a chronic neuropathic pain condition that occurs after injury to a limb. After the injury heals, the pain persists. “The exact mechanisms behind CRPS are not clear, but the initial injury triggers a firing of neurons in the patient’s central nervous system that is perceived by the body as chronic pain,” explains Dr. Clarke. “Essentially the brain keeps a memory of the pain even after the injury has healed.”

The diagnosis was life changing for Judy. “It may sound strange but I was extremely relieved,” says Judy. “The pain I was experiencing was not logical. There’s a certain relief in knowing what’s wrong with you and working towards management of the condition.”

Under the care of Dr. Clarke, Judy has seen improvements to her health through a variety of treatments. These have ranged from pharmaceutical therapies to a spinal cord stimulator. Judy has also participated in pain research at Lawson. Judy sees her participation as a way to give back to London’s medical and research community, and help future generations of patients.

After breaking her wrist six years ago, Judy Williams was diagnosed with complex regional pain syndrome (CRPS), a chronic neuropathic pain condition that occurs after injury to a limb. Even after the injury is healed, pain persists.

DRIVING PAIN RESEARCH FORWARD

London, Ontario is home to a large multidisciplinary pain research team with collaborators across Lawson, London Health Sciences Centre, St. Joseph’s and Western University. A primary area of interest for these researchers is neuropathic pain.

In 2008, Dr. Dwight Moulin, a Lawson scientist and neurologist at St. Joseph’s Pain Management Clinic, spearheaded a national collaborative team that set up a neuropathic pain patient registry. This registry has recruited over 800 patients to the Canadian Neuropathic Pain Database. The powerful tool has allowed neuropathic pain researchers across Canada to collaborate on nine studies published in leading pain research journals.

In one of these studies, led by Dr. Moulin, researchers examined the long-term outcomes of patients who visit pain clinics to manage neuropathic pain conditions like CRPS.

Patients were followed over one year to study any improvements in pain intensity, quality of life and other treatment outcomes. Researchers found that at 12 months only 23.7 per cent of patients experienced significant improvements. “This study shows that only one in four patients get adequate pain relief,” says Dr. Moulin. “This suggests that our current treatments are not good enough. We need more research to better understand and treat chronic neuropathic pain.”

USING MRI TO STUDY COMPLEX REGIONAL PAIN SYNDROME (CRPS)

Lawson researchers are conducting a number of studies to better understand neuropathic pain. In one project Dr. Keith St. Lawrence, a Lawson Imaging scientist, collaborated with Drs. Clarke and Moulin to study brain plasticity, defined as lasting changes to the brain, in patients with CRPS.

“Previous studies have shown that there are structural changes to the brains of patients with CRPS,” says Dr. St. Lawrence. “However, little was known about the differences in brain changes between patients at initial diagnosis and those with later-stage CRPS.”

The researchers used a number of magnetic resonance imaging (MRI) techniques to image the brains of early- and late-stage CRPS patients recruited from St. Joseph’s Pain Management Clinic. With MRI technology available at Lawson, they were able to study both the structure of the brain by looking at the volume of gray matter in different areas and brain function by looking at blood flow.

The researchers discovered different patterns of brain changes between the two groups. In early-stage CRPS patients, they found shrinkage in the volume of grey matter in areas of the brain associated with motion – the sensorimotor and parietal cortices. They also saw a decrease in blood flow in an area of the brain associated with emotional response to pain – the limbic system.

Late-stage patients were different. Researchers found that patients with higher pain levels experienced more shrinkage in the volume of grey matter in areas of the brain associated with pain processing. Meanwhile, no changes were detected in areas of the brain associated with emotional response to pain.

“This research could provide clues as to why pain persists in patients with CRPS,” says Dr. St. Lawrence. “It’s showing there are unique early changes to the brain. This highlights how an injury to a limb can cause alterations in the central nervous system.”

The researchers hope their findings might also provide clues for improving treatments. They want to further study whether they can predict a patient’s response to treatment based on early changes they see in the brain. They also hope their research can lead to new treatments, perhaps by targeting areas of the brain that are changing.

This is an exciting prospect, especially for CRPS patients like Judy Williams who participated in the study. “When Dr. Clarke approached me about joining the study, I saw it as my chance to give back,” says Judy. “Most people don’t understand chronic pain. I want to do whatever I can to help others. If we can link this to the prevention or treatment of CRPS, that’s amazing.”

“Recognizing the burden of chronic pain, our team is committed to research in this field,” says Dr. Clarke. “Utilizing state-of-the-art neuroimaging technologies, we have been able to look into the brain to see changes that occur in those with CRPS.”

Lawson researchers such as Dr. Dwight Moulin (left) and Dr. Keith St. Lawrence (right) are conducting studies to gain more understanding of neuropathic pain and improve treatments.

UNDERSTANDING THE INDIVIDUAL EXPERIENCE OF PAIN

Researchers are also looking at psychological factors associated with chronic pain. There is a growing interest in how these factors influence patient outcomes. In one project, researchers studied catastrophizing and its relation to patient outcomes. Catastrophizing is a tendency to focus on, exaggerate and feel helpless towards pain. “We often see catastrophizing in those with high anxiety levels,” says Dr. Moulin. “The injury might be minor but their experience of it is magnified by their psychological state.”

The study, led by Dr. Melanie Racine, formerly a Lawson trainee and current research associate at Western University, recruited 538 patients from across Canada as part of the Canadian Neuropathic Pain Database, including those recruited from St. Joseph’s Pain Management Clinic. The research participants were asked to complete measures of their own catastrophizing and pain intensity when first seen in the clinic and then at three and six-month follow-up appointments. The study showed that when catastrophizing was reduced early in treatment, it predicted improvement in pain intensity later in treatment. Similarly, improving pain intensity early in treatment predicted a reduction in catastrophizing later in treatment.

“These results suggest that treatments targeting catastrophizing might positively influence other pain outcomes and vice versa,” says Dr. Moulin. “There may be multiple paths to achieving positive outcomes.”

Cognitive behavioural therapy (CBT) is currently the most common psychosocial treatment for addressing pain-related catastrophizing. This research suggests that CBT could be beneficial as an alternate therapy for patients with neuropathic pain.

Through continued work, Lawson researchers are working to advance knowledge of neuropathic pain and uncover even more potential therapies for patients like Judy Williams in the future.

WHAT IS CHRONIC NEUROPATHIC PAIN?

•  Chronic neuropathic pain results from a disease or damage that affects nerves in the somatosensory system.

•  The somatosensory system is part of the peripheral and central nervous system that is linked to sensory receptors throughout the body.

• The system helps the brain to understand what an individual is feeling both inside and on the surface of their body.

•  With neuropathic pain, nerves become damaged and send pain signals to the brain.

• Neuropathic pain conditions include complex regional pain syndrome (CRPS) and nerve pain due to diabetes and shingles.

Dr. Collin Clarke is a part of the Imaging research program at Lawson. He is an assistant professor in the Department of Anaesthesia and Peri-Operative Medicine, Schulich School of Medicine & Density at Western University.

Dr. Dwight Moulin is a part of the Neurological Disorders research program at Lawson. He is the Earl Russell Chair, Pain Medicine and a professor in the Departments of Clinical Neurological Sciences and Oncology, Schulich School of Medicine & Dentistry at Western University.

Dr. Keith St. Lawrence is a part of the Imaging research program at Lawson. He is an associate professor in the Departments of Medical Biophysics and Medical Imaging, Schulich School of Medicine & Dentistry at Western University.