Androgen hormones regulate the production on the pain-inducing inflammatory molecule IL-1β in a mouse model of inflammatory pain

Chronic pain prevalence varies between sexes with a higher incidence and duration reported in women compared to men. This disparity suggests that biological factors, such as sexual hormones, may influence pain perception and development. Among the key players in pain mechanisms, interleukin-1 beta (IL-1β), an inflammatory molecule, has been identified to activate neurons involved in pain sensation. This study explores the hypothesis that sexual hormones, particularly androgens, regulate IL-1β production in inflamed tissues, thereby influencing pain responses. To investigate this, we induced inflammatory pain in male and female mice using Complete Freund’s Adjuvant (CFA), injected into the hind paw. To assess the effect of sex hormones on the production of IL-1β and pain, we modulated the levels of sex hormones by surgical and pharmacological approaches: ovariectomy, orchidectomy, and administration of flutamide, an androgen receptor antagonist. The analysis of IL-1β levels was conducted through quantitative Polymerase Chain Reaction (QPCR). We measured mechanical pain sensitivity thresholds using the von-Frey method. Our results indicate that injection of CFA drastically increased the levels of IL-1β in the inflamed skin. Blocking IL-1β significantly reduced pain sensitivity. We found decreasing systemic androgen levels, by orchidectomy or flutamide, significantly increase IL-1β expression and pain recovery times. Overall, we found that androgens reduce the levels of IL-1β and facilitate the resolution of pain. These findings underscore the intricate relationship between sexual hormones and inflammatory mediators in the context of chronic pain, suggesting potential avenues for developing sex-specific pain management strategies that target the hormonal regulation of inflammatory pathways.