Cardiac Stress in Intimate Partner Violence: The Role of Pain in Cardiovascular Disease Risk

Intimate partner violence (IPV) is a gendered epidemic disproportionately impacting women: two-thirds of victims identify as female. Globally, 35% of women report violence in a personal relationship with higher levels of unreported abuse. Cardiovascular disease is higher in females who experience IPV compared to males, although the mechanisms for these sex differences are unknown. Among the effects of IPV is chronic pain. Pain affects cardiac function and increases cardiovascular disease risk through similarly unknown mechanisms. We sought to determine how pain impacts the heart through sex-dependent pathways to explain sex differences in the connection between IPV and cardiovascular disease. Female and male C57Bl/6 mice (8-10 weeks old) were anesthetized and exposed to the spared nerve injury model of neuropathic pain, where the tibial and common peroneal branches of the sciatic nerve are severed and the sural branch is left intact. Mice recovered for 5 or 30 d and hearts were extracted for analysis. Cardiac myofilament activity was measured with a colourimetric assay for ATP consumption. Myofilament protein phosphorylation was assessed with ProD Diamond staining and collagen levels were quantified by spectrophotometry. Key elements of the RISK and SAFE signaling pathways were quantified by immunoblotting as markers of stress. Proteomic analysis was done by LC-MS/MS. Cardiac myofilaments had a significant increase in calcium sensitivity at 5 and 30 d in females, with no change in males. Phosphorylation of troponin T, tropomyosin, and myosin light chain 1 decreased in females by 30 d with only a transient decline in desmin and myosin light chain 1 phosphorylation in males at 5 d. STAT3, Akt, ERK1/2, and p70S6K had reduced activity in hearts from females at 5 and 30 d as indicated by decreased phosphorylation, while only ERK1/2 phosphorylation was decreased in males at 30 d. Proteomic analysis found 634 proteins whose expression or posttranslational modifications were altered at 5 or 30 d. Sex differences of >50% were detected in 400 proteins at 5 d and 490 at 30 d. These results reveal an increase in myofilament ATP consumption and a reduced baseline activity of the cardioprotective RISK and SAFE pathways in the hearts of female mice subjected to pain, but not males. Higher myofilament ATP consumption and reduced baseline activity of RISK and SAFE diminishes the ability of the heart to respond to stress, and could explain the increased risk of cardiovascular disease mortality in females who experience IPV. This work was supported with a National Women’s Health Research Initiative Catalyst grant from the Canadian Institutes of Health Research. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.