Elucidating the role of testosterone in activity-induced muscle pain in male and female mice

Chronic pain affects over 100 million Americans, with musculoskeletal conditions impacting 20-30% of the population. Despite chronic pain being more prevalent in females, most preclinical studies focus on male animals, limiting translation into human populations. Although testosterone may protect males from the development of chronic pain, there are very few research studies on testosterone and pain. Further, the insufficient reporting of scientific elements, such as blinding, randomization, statistical analysis, and sex of subject, further limits the progress in the pain field. Therefore, this work analyzed the reporting of these rigor characteristics in the journal PAIN and the role of testosterone in both male and female mice in a mouse model of activity-induced muscle pain. In analyzing the reporting of these elements in the journal PAIN, I found there has been an increase in reporting randomization and blinding in preclinical data, although this reporting was lower than clinical research. While utilization of both sexes remains high in clinical studies, the disaggregation of data by sex remains relatively low in both clinical and preclinical research. Investigating testosterone's role in activity-induced muscle pain, I found that the conversion to estradiol and activation the ER-α in the rostral ventromedial medulla (RVM) protects against pain in males. In females, testosterone increases serotonin signaling in the RVM and activation of androgen receptors decreases widespread pain.