Senescent mechanism in older patients with chronic pain

Abstract

The prevalence and the associated burden of low back pain (LBP) increase with age; however, research on LBP has primarily focused on young people and adults, and little attention has been given to the elderly population. Given that older adults are susceptible to LBP, the mechanism of geriatric chronic pain remains unexplained. Senescent cells involving irreversibly proliferative arrest can develop the SASP, consisting of proinflammatory cytokines and extracellular matrix-degrading proteins, which function as deleterious paracrine and systemic mild inflammation. Chronic inflammation is well known as a senescence-associated secretory phenotype (SASP), which produces numerous proinflammatory cytokines leading to age-related inflammation ( "inflammaging" ). Age-related low muscle mass (sarcopenia) and/or intramuscular fat deposition (sarcopenic obesity), which are associated with geriatric LBP, are considered part of systemic inflammation. In sarcopenia, age-related loss of trunk muscle mass follows a decrease in skeletal muscle mass of the extremities, which leads to poor spinal sagittal balance and subsequent LBP. On the other hands, pathological changes in the posterior horn of the spinal cord and/or peripheral nerve system also adversely affect the pain sensitivity of the elderly with aging. As above, we consider that the mechanism of senescence and the development of chronic pain are closely related. However, since there are no clinically useful biomarkers for senescence in the elderly, we focused on the fact that chronic inflammation associated with senescence causes a decrease in skeletal muscle mass and an increase in fat mass. Thus, we have been addressing the research to find the body compositional changes that are indicators of the development of chronic pain in the elderly. Focusing on the skeletal muscle-fat ration from the viewpoint of the mechanism of senescence as an evaluation of the threshold of body composition that causes chronic pain in the elderly, we demonstrated that skeletal muscle mass 2.5 times the fat mass of the lower extremities should be maintained as an index of exercise therapy.