Diet-induced Obesity Leads to Behavioral Indicators of Pain Preceding Structural Joint Damage in Wild-Type Mice.

Abstract

Introduction: Obesity is one of the largest modifiable risk factors for the development of musculoskeletal diseases, including intervertebral disc (IVD) degeneration and back pain. Despite the clinical association, no studies have directly assessed whether diet-induced obesity accelerates IVD degeneration, back pain, or investigated the biological mediators underlying this association. In this study we examine the effects of chronic consumption of a high-fat or high-fat/high-sugar (western) diet on the IVD and pain-associated outcomes. Methods: Male C57BL/6N mice were randomized into one of three diet groups (control chow; high-fat; high-fat, high-sugar western diet) at 10-weeks of age and remained on the diet for 12, 24 or 40 weeks. At endpoint, animals were assessed for behavioral indicators of pain, joint tissues were collected for histological and molecular analysis, and IBA-1, GFAP and CGRP were measured in spinal cords by immunohistochemistry . Results: Animals fed obesogenic (high-fat or western) diets showed behavioral indicators of pain beginning at 12 weeks and persisting up to 40 weeks of diet consumption. Histological indicators of joint degeneration were not detected in the IVD or knee until 40 weeks on the experimental diets. Mice fed the obesogenic diets showed increased intradiscal expression of inflammatory cytokines and circulating levels of MCP-1 compared to control. Linear regression modeling demonstrated that age and diet were both significant predictors of most pain-related behavioral outcomes, but not histopathological joint degeneration.Conclusion: Diet-induced obesity accelerates IVD degeneration and knee OA in mice; however, pain-related behaviors precede and are independent of histopathological structural damage. These findings contribute to understanding the source of obesity-related back pain and the contribution of structural IVD degeneration.

Age-associated changes in knee osteoarthritis, pain-related behaviors, and dorsal root ganglia immunophenotyping of male and female mice

“…One study evaluated pain behaviors and joint damage in the context of diet-induced obesity. This study reported obesity from a high-fat or Western diet (HFD) resulted in pain behaviors (increased mechanical sensitivity and altered spontaneous locomotion) in 24-week and 40-week old mice compared to 12-week old mice, and these behaviors preceded joint damage (61). Though the authors did not statistically report difference between age groups (only between different diet groups), if one looks at the chow-fed mice from 12-weeks to 40-weeks of age there is a decrease in spontaneous locomotion and increase in osteophytes in these aged mice, which is consistent with our findings.…”

The cGAS-STING pathway affects vertebral bone but does not promote intervertebral disc cell senescence or degeneration

“…The findings in the disc do however align with the recent work of Gorth et al in hTNF-α overexpression mouse models and contribute to a growing body of evidence demonstrating the marginal impacts of systemic inflammation on overall disc health (30,61). Other in vivo models of systemic inflammation, including high fat diet-induced obesity, have shown disc architecture is not negatively impacted by inflammatory conditions that are not local (62,63). As seen in the structurally intact discs of these models, N153S NP tissues retained healthy, vacuolated cells expressing the NP-phenotypic marker CA3 and an aggrecan-rich matrix.…”