The Influence of Sex Hormones on Osteoarthritis Pain Perception in Mice

Abstract

Introduction: Despite the higher prevalence of osteoarthritis (OA) in women, animal studies are primarily performed in young male mice. There is evidence that cartilage degeneration is more severe in male mice which can be explained by the protective effect of estrogen against OA in females. This aligns with the onset of OA often occurring after menopause in women. This proposed study will assess the potential limitations of using male mice by evaluating the differences in OA pain perception between male and female mouse models, and the role of sex hormones.

Methods: A total of 96 mice will be used, split into four groups (n = 12) within their sex: sham, sham + ovariectomized (OVX)/orchiectomized (ORX), destabilization of the medial meniscus (DMM), and DMM + OVX/ORX. Half of the female (n = 24) and male mice (n = 24) will then receive DMM surgery to induce post-traumatic OA. Electronic von Frey (EvF) will be used to measure mechanical allodynia and Pressure Application Measurement (PAM) will assess knee hyperalgesia. Open field testing (OFT) will evaluate locomotor and behavioural activity. Twelve weeks after DMM, all mice will be sacrificed, and knee histological sections will be taken to assess for OA damage using the OARSI and synovial scoring system.

Anticipated Results: Higher overall measures of pain, indicated by EvF, knee hyperalgesia, OFT and synovium analysis, are anticipated in intact female mice than in intact male mice. ORX mice will likely experience more allodynia/hyperalgesia than intact male mice and OVX mice will likely experience less allodynia/hyperalesia than intact female mice. Intact DMM female mice will have increased effusion-synovitis at a worse grade than intact DMM male mice. ORX males will experience less severe OA than intact male mice and OVX females will experience more severe OA than intact female mice.

Discussion: Anticipated differences between the pain response between male and female mice show that the use of exclusively male mice is a limitation in OA-associated pain research.

Conclusion: This novel study considers the role of sex hormones on the pain perception of OA.