Research and Education Highlights
Combining Brain Imaging Technologies and Behavioural Studies to Better Understand Pain
Dr. Karen Davis is a senior scientist and heads the Division of Brain, Imaging & Behaviour Systems at Toronto Western Research Institute. She is cross-appointed as a professor in the Department of Surgery and the associate director for the Institute of Medical Science at the University of Toronto. Dr. Tim Salomons is one of her post-doctoral fellows. Together they are combining their expertise in MR-based technologies and behavioural and psycho-physical studies to better understand pain.
Davis describes her research as, “Looking at how pain is represented in the brain structurally and functionally and at the abnormalities that arise when you have an injury or develop chronic pain.” They use several MR-based techniques in her lab to produce images of the brain during pain. Functional MRIs generate images of areas of the brain that become activated when a painful stimulus is delivered to subjects. These techniques are also useful in identifying how areas of the brain are connected functionally, even when a stimulus is not being delivered, as so can be used to examine brain networks during spontaneous chronic pain. Structural MRI techniques are used to look at both the grey matter and white matter connections in the brain. In the past, Davis’ lab has used chronic pain populations with irritable bowel syndrome, temporomandibular disorder and peripheral nerve injuries as model systems to identify abnormalities in various chronic pain states.
Salomons jokes that he, “Used to be the pain guy in the psychology lab” during his graduate work, but now is “the psychologist in the pain lab.” His interest in studying pain began when he was working with post-traumatic stress patients who were having painful flashbacks because it suggested they actually were experiencing a sensory memory. He sought out the mentorship of Dr. Joel Katz who had previously studied phantom limb pain which can also be conceptualized as a memory of pain. Over time Salomons moved away from researching typical psychological disorders towards pain research.
Davis’ interest in electrophysiology and pain research was influenced by some of her high school teachers. In high school she was exposed to several modules on the brain around the time that opioid receptors were discovered. Her interest grew in first-year biology under the instruction of Dr. Bruce Pomeranz who she worked with part-time for 2 years. She remembers reading in her first-year of university about xenon inhalational technology as a brain imaging technique (before PET or MR-technologies existed) that produced fuzzy images of the brain’s response when subjects were reading or writing and thinking that one day this type of technology would make it possible to study the whole brain instead single cell electrophysiology. Her doctoral research was under the direction of Dr. Jonathon Dostrovsky who was studying stimulation-produced analgesia to tap into parts of the brain to produce endogenous analgesia or activate the antinociceptive system. These interests were expanded during her PhD studies and, together with Dr. Dostrovsky, she conducted electrophysiololgical studies to map out central pathways involved in vascular headaches for her PhD since stimulation produced analgesia.
Davis and Salomons have combined their physiology and psychology backgrounds to study if individual differences in how people feel and respond to injury contribute to how pain is perceived. They are particularly interested in why some people with acute pain go on to develop chronic pain conditions and others do not. They have been studying brain plasticity to determine how the brain responds in good or bad ways to repeated pain exposure. Davis comes from a bottom-up approach and looks at how peripheral input might drive brain processing; whereas, Salomons comes from a top-down perspective and is interested in how an individual’s thoughts and feelings could alter brain processing of pain. They are trying to determine if abnormalities in the brains of chronic pain patients represent existing vulnerabilities or are the result of long-term pain experiences or input. This has led them to consider the possibility of adaptive plasticity. A hypothetical example of adaptive plasticity would be a positive alteration in pain processing in a chronic pain patient who takes up meditation, exercise or physiotherapy. They have recently published an article in the European Journal of Neurology where they suggest that the structure of grey matter and connectivity of white matter are associated with the attribute of helplessness, or the degree to which patients found their chronic pain to be controllable.
Davis’ lab has published other studies that demonstrate the relationships between cognitive coping strategies and pain responses. They showed that there were two types of pain responders when they performed functional MRIs on healthy participants’ reaction times to a cognitively demanding task (Stroop®) during noxious stimulation (Seminowicz, Mikulis, & Davis, 2004). One group’s reaction times were negatively impacted by the pain as expected and their Stroop® reaction times slowed down; however, the other group’s reactions times actually improved with pain. The participants in this study who had faster reaction times reported trying hard not to let pain bother them. The lab is currently following-up with imaging studies to determine how the brains of these two subgroups of individuals are similarly or differently organized.
Seminowicz DA, Mikulis DJ, & Davis KD. 2004. Cognitive modulation of pain-related brain responses depends on behavioral strategy. Pain, 112, 48-58.
http://www.ncbi.nlm.nih.gov/pubmed?term=Cognitive%20modulation%20of%20pain-related%20brain%20responses%20depends%20on%20behavioral%20strategy
In another line of study, Davis’ lab uncovered several sex differences in pain sensitivity. When healthy male and female participants were exposed to a thermostimulus and asked to rate their pain on a VAS scale they noticed that women had a lower pain threshold. Similar findings have recently been reported in a Globe and Mail article and in the Journal of Pain. However, Davis’ group found that this was not the full story. While women had a lower pain threshold initially, they adapted dramatically to the pain after 20 seconds of being exposed to the stimulus. Furthermore, when women were given a second stimulus after the initial test they had habituated and this allowed them to experience less pain over time. Neither adaptation nor habituation were observed to the same degree in the male participants. Davis group are planning to follow up with this finding using imaging studies.
Hashmi JA & Davis KD. 2009. Women experience greater heat pain adaptation and habituation than men. Pain, 145, 350-357.
http://www.ncbi.nlm.nih.gov/pubmed/19632779
Davis' lab continues to follow-up the findings of their previous studies on sex differences and behavioral strategies using MR-based technologies.