Sex-Dependent Mechanical Allodynia in Co-Morbid Hypertension and Osteoarthritis

Abstract

Despite the common comorbid presentation of hypertension and osteoarthritis (OA), the relationship between these two diseases is often over-simplified as a result of limited physical activity in these populations. However, in the clinical population, there is a significant relationship between hypertension and both symptomatic and radiographic knee OA. Interestingly, aged spontaneously hypertensive rats (SHR) have spontaneous joint damage shown through micro-CT and histopathology compared to age matched non-hypertensive controls; however, the pain phenotype in these animals is unknown. Thus, the purpose of this study was to characterize the 50% withdrawal threshold in SHR animals to explore the pathophysiological interactions between hypertension and OA. OA was induced in female and male SHR animals via medial collateral ligament transection and medial meniscus transection (MCLT+MMT), with skin incision used as a sham control (n=7-8/group/sex). Mechanical allodynia was assessed at the ipsilateral hind paw at baseline, then every other week for 8 weeks post-op. The 50% withdrawal threshold was calculated using Chaplan's up-down application method of von Frey filaments. In female MCLT+MMT animals, 50% withdrawal threshold decreased from baseline to weeks 2 and 4 (p's<0.05). In female sham animals, this decrease was only seen at week 4 (p<0.05). No week-to-week differences were observed in male animals of either group. In the MCLT+MMT group, sex differences were observed at weeks 2, 4 and 6 (p's<0.05) while in the sham group, sex differences were only seen at week 4 (p<0.05). Finally, at this sample size, no effects due to OA were observed for either sex. Female hypertensive animals experience lower withdrawal thresholds compared to males, regardless of joint pathophysiology. Interestingly, sex differences were more prevalent in the MCLT+MMT group, indicating a possible sex-dependent interaction between hypertension and OA progression; however, further research should implement more sensitive pain-assessment techniques to determine these interactions. Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R01AR071431 and F31 AR077996.