Chronic
low back pain is a major cause of disability and health care costs. Current treatments are inadequate for many patients. A number of preclinical models have been developed that attempt to mimic aspects of clinical conditions that contribute to
low back pain. These involve application of nucleus pulposus material near the lumbar dorsal root ganglia (DRG), chronic compression of the DRG, or localized
inflammation of the DRG. These models, which are primarily implemented in rats, have many common features including behavioral
hypersensitivity of the hindpaw, enhanced excitability and spontaneous activity of sensory neurons, and locally elevated levels of inflammatory mediators including
cytokines. Clinically,
epidural injection of
steroids (
glucocorticoids) is commonly used when more
conservative treatments fail, but clinical trials evaluating these treatments have yielded mixed results. There are relatively few preclinical studies of
steroid effects in
low back pain models. One preclinical study suggests that the
mineralocorticoid receptor, also present in the DRG, may have pro-inflammatory effects that oppose the activation of the
glucocorticoid receptor. Although the
glucocorticoid receptor is the target of anti-inflammatory
steroids, many clinically used
steroids activate both receptors. This could be one explanation for the limited effects of epidural
steroids in some patients. Additional preclinical research is needed to address other possible reasons for limited efficacy of
steroids, such as central sensitization or presence of an ongoing inflammatory stimulus in some forms of
low back pain.