Immunology and Pain

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Josiane C.S. Mapplebeck
BSc, Third year PhD Student, Department of Physiology, University of Toronto

Supervisor: Dr. Michael Salter
Chief of Research, Hospital for Sick Children
Professor, Institute of Medical Science and Faculty of Dentistry

By: Kasey Hemington

When you meet her, you can just tell; Josiane Mapplebeck is incredibly passionate about her research on the role of microglia in chronic pain. I sat down with Mapplebeck to discuss her recently published work in Nature Neuroscience, demonstrating sex differences in the way in which the immune system mediates pain hypersensitivity.1

Though Mapplebeck is only in the third year of her PhD in Physiology at the University of Toronto, she became involved in pain research over six years ago while interning in Dr. Jeffrey Mogil’s lab at McGill University. After working on a number of pain-related projects, she turned to sex differences research while being mentored by fellow Mogil lab member Dr. Robert Sorge, telling me, “It was the first project in research where I was 100% engrossed—I wanted to figure out what was happening in females.” In 2013, Mapplebeck moved to Toronto, allowing her to continue what she had started by undertaking a PhD in Physiology.

Mapplebeck’s recent publication revolves around microglia, which are known to mediate pain hypersensitivity in rodent models of neuropathic pain (chronic pain resulting from nervous system damage). These immune cells are responsible for the dynamic interplay between the central nervous system and the immune system, releasing substances such as brain-derived neurotrophic factor that acts on neurons in pain pathways. The catch, Mapplebeck has realized, is that this relationship really only applies to male rodents—often the only sex included in a given experiment. Mapplebeck has been working in Dr. Michael Salter’s laboratory at the University of Toronto, designing experiments investigating neuropathic pain that include both sexes, and showing that males and females exhibit similar hypersensitivity following nerve injury. Through a series of elegant experimental manipulations, Mapplebeck was shocked to discover that killing microglia, or blocking the microglia-neuronal signaling pathway reversed pain hypersensitivity in male mice as expected, but not at all in female mice.

The implications for the field of chronic pain research are substantial: “Several clinical trials have attempted to develop treatments for chronic pain in humans by inhibiting microglial function. However, microglia may not be relevant in females. This sex difference completely changes how we see drug development and shows that we might need sex-specific drug targets,” Mapplebeck explains. “This was the first time I felt I was doing a project that had real life implications. There is a lot of chronic pain in females, but the majority of rodent research is done in males—I realized my project could improve women’s health.”

Mapplebeck is grateful to her supervisor Dr. Salter, Chief of Research at the Hospital for Sick Children, for promoting independent investigation and providing her with extraordinary opportunities to advance her research. When asked about future plans, she tells me she’s committed to making a career out of sex differences and pain, and eventually becoming a principal investigator. Given her recent success and passion for the pursuit of knowledge, she is well on her way to achieving her goals.

  1. Sorge RE, Mapplebeck JCS, Rosen S, et al. Different Immune Cells Mediate Mechanical Pain Hypersensitivity in Male and Female Mice. Nature Neuroscience 2015;18(8): 1081–83.