Title: The role of Oncostatin M in the human dorsal root ganglia
Presenter: Juliet Mwirigi, PhD student, UT Dallas, US
Methodology, findings and conclusions of the research
Our research project is focused on examining the role of a cytokine, Oncostatin M (OSM), in driving pain by activating sensory neurons and peripheral immune cells. Our rationale for studying OSM stems from previous findings showing that OSM gene transcripts are upregulated in the dorsal root ganglia (DRG) of patients with chronic low back pain. To investigate the role of OSM in a biologically relevant model, we utilized human DRG tissue procured from our local transplant site. Our experimental projects followed two general aims. The first aim was to investigate the expression profile of OSM receptors in DRG neurons and surrounding immune cells whilst considering sex differences. The second aim was to assess the functional outcomes of treating live human DRG with OSM. The findings of this study demonstrate that OSM receptors are expressed in a subset of nociceptors and surrounding glial-like cells with potentially higher expression in male DRGs. From our functional immunostaining experiments, we observed an increase in OSM-evoked signaling, indicating that OSM can activate neurons and glial cells at the periphery. Overall, these findings highlight the role of OSM in driving pain and underscore the importance of using human tissue to improve translatability of preclinical pain research.
Implications of the research for understanding migraine and/or its comorbidities
Although many clinical studies have consistently linked increased peripheral cytokine levels to migraine disorders, we do not have a full picture of how they contribute to migraine pathology. One explanation is that many migraine studies with human samples are limited to measuring serum levels of cytokines. These approaches may not completely reflect the underlying molecular mechanisms by which cytokines contribute to migraine symptoms and pathophysiology. Although our study was primarily performed in human DRG, it has important implications for using human tissues from organ donors to answer other relevant pain research questions. For example, migraine researchers can explore the possibility of procuring trigeminal tissue from organ donors to drive migraine research.