Article by Stacey J Butler
Graphic design by Michie (Xingyu) Wu
Our brains are incredibly powerful. Even when we are not conscious and our bodies are at rest, the brain is still working hard. The brain allows us to feel joy, happiness, and pleasure. But it also is the reason that we feel pain. Pain researchers use neuroimaging to try and understand how pain is “created” in the brain, and how brain plasticity may contribute to conditions such as chronic pain. With these advanced neuroimaging techniques, Natalie Osborne, a PhD Candidate in the Institute of Medical Sciences (IMS), is furthering our understanding of sex-differences in chronic pain.
Natalie’s journey to the IMS, and her quest to study chronic pain, began with her Master’s research at the University of Western Ontario. Under the supervision of Dr. Adrian Owen, Natalie learned how to use functional magnetic resonance imaging (fMRI) to measure cognition in patients with disorders of consciousness (DOC). Patients with DOC vary in their level of consciousness, from being in a coma to being awake but unable to communicate. At the bedside, patients may show no signs of awareness. But under the fMRI scanner, some patients are able to mentally respond to commands. Even though they were not able to physically move, their brains still responded to a command such as imagining themselves playing tennis. Natalie was amazed by the power of our brains, which she got to witness first-hand. Her fascination grew when she met a patient who recovered from a vegetative state and they “brought him back to the lab to see if he remembered anything from his first visit, and he did!” This led Natalie to wonder what else these patients are experiencing and are unable to tell us. One question was at the forefront of her mind: “Are you in pain?”. Natalie wrote about this topic in the Summer 2017 issue of IMS Magazine, with her compassionate article entitled, ‘I feel, therefore I am? Understanding pain in disorders of consciousness’.
The search for the answer to this important question drove Natalie to pursue her PhD with Dr. Karen Davis, a renowned researcher in chronic pain, at the University of Toronto. Along with a common interest in neuroimaging, the two researchers also shared a commitment to gender equality in science. Historically, women are underrepresented in research. 1 Many studies that do include women, fail to analyze results separately by sex.1 Women and men can differ in their symptoms and the way they respond to treatments.1,2 With regards to chronic pain, women are more likely to be affected than men.1,2 Too often however, women with chronic pain are dismissed by healthcare providers.2 Natalie believes this happens due to lack of preclinical and clinical research on how sex and gender influence pain3, disparities in funding for research on female-specific conditions4, biases and gender stereotypes about pain expression5, and general misunderstanding about chronic pain. Patients with chronic pain are often told that “It is all in their head”. Although this statement is technically true–after all our brain does tell us we are in pain–it is also misleading. Worst of all, it leaves patients feeling helpless and stigmatized. Patients should be reassured that what they are experiencing is in fact real and valid. Better yet, they may even be able to use the power of their brain to control their pain and find relief.
In her PhD research, Natalie strives to understand how the brain functions in patients with conditions that cause chronic pain. She studies conditions that are more common in males (ex. Ankylosing Spondylitis) as well as female-dominant conditions (ex. Carpal Tunnel Syndrome). This approach is a unique way to account for sex-differences and has led to interesting findings. Natalie found abnormalities in a region called the subgenual anterior cingulate cortex. This region is a key node in the descending antinociceptive system, which is associated with the brain’s ability to modulate pain. Surprisingly, the abnormalities were only present in patients of the non-dominant sex.6,7 Chronic pain is complex, but these results provide valuable insights into how connections in the brain and pain processing can differ among sexes. It also helps to uncover reasons why females may develop a predominantly male condition and vice versa. Most notably, it underlines the importance of considering sex and gender in research.
Natalie is keen to ensure her research has an impact. She shares the results of her research on Twitter in a way that is easily accessible for everyone. During her time with our team at IMS Magazine, she held almost every role possible, most recently leading as the Editor-in-Chief. Her first issue was, unsurprisingly, Women’s Health (Summer 2019). For Natalie, working on the magazine enhanced her graduate school experience and was a source of motivation for her own thesis work. She felt energized discussing with her peers the current hot topics in science and the exceptional research being done in the IMS. Natalie emphasizes that communicating research in a way that is easily understood requires a lot of training and gets easier with practice. It is not something that comes naturally to most scientists. The devastating impact of misinformation, or poorly communicated science, became all too clear during the pandemic. Natalie felt inspired by other scientists on Twitter, who have taken it upon themselves to increase accessibility, stop the spread of misinformation, and share the real evidence.
Completing a PhD thesis is already an incredibly challenging task–some may even equate it to climbing Mount Everest. Therefore, completing a PhD thesis during a global pandemic would be like climbing Mount Everest in a blizzard, with hurricane level winds. Although it was difficult, this experience helped Natalie learn how to be more adaptable, a trait that she can surely carry with her beyond graduate school. Wherever the road leads Natalie next, she will continue to advocate for women’s health and patient-centered research. She will keep using her brain to help us understand the power of ours.
- Mazure CM, Jones DP. Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Womens Health, 2015; 15:94.
- Billock J. Pain bias: The health inequality rarely discussed. BBC Future, The Health Gap, 2018 May 22. [cited Oct 14 2021]. Available from: https://www.bbc.com/future/article/20180518-the-inequality-in-how-women-are-treated-for-pain
- Mogil, J.S. Qualitative sex differences in pain processing: emerging evidence of a biased literature. Nat Rev Neurosci, 2020; 21:353–365.
- Mirin AA. Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health. J Womens Health (Larchmt). 2021; 30(7):956-963.
- Zhang L, Losin EA, Ashar YK, Koban L, Wager TD. Gender biases in estimation of others’ pain. J Pain, 2021; 22(9):1048 – 1059.
- Osborne NR, Cheng JC, Rogachov A, Kim JA, Hemington KS, Bosma RL, Inman RD, Davis KD. Abnormal subgenual anterior cingulate circuitry is unique to women but not men with chronic pain. Pain, 2021; 162(1):97-108.
- Osborne NR, Anastakis DJ, Kim JA, El-Sayed R, Cheng JC, Rogachov A, Hemington KS, Bosma RL, Fauchon C, Davis KD. Sex-Specific Abnormalities and Treatment-Related Plasticity of Subgenual Anterior Cingulate Cortex Functional Connectivity in Chronic Pain. Front Pain Res, 2021; 9.