Modeling human lumbar spinal osteoarthritis and low back pain through preclinical studies

Abstract

Low back pain (LBP) is a prevalent condition and the primary cause for global disability. This is likely a result, in part, of poor pain management that stems from a lack of understanding of the pathophysiological mechanisms that contribute to this complex condition. To better understand the underlying mechanisms of LBP, we use preclinical animal pain models to mimic the human condition and examine the neurobiological processes induced from spine‐related tissues that contribute to pain. We are currently investigating two common causes for LBP, lumbar facet joint degeneration and muscle pain. Facet joint degeneration that is consistent with spinal osteoarthritis (OA) has distinctive patterns of histopathological findings. We wanted to determine if a rat model of lumbar vertebral segmental hypomobility induces degeneration that replicates these characteristic findings to mimic spinal OA. We performed time‐dependent investigations to determine the location, severity, and progression of histopathological changes to the articular cartilage following the onset of hypomobility. Our findings suggest that lumbar spine hypomobility induces facet joint histopathological changes that mimic spinal OA histopathology, location (patterning), and progression. We have also identified the potential contribution of adjacent joint tissues including the synovium, capsule, and subchondral bone in the onset and progression of OA. The low back muscles are also a clinically relevant source of LBP. We are investigating a rat model to mimic chronic low back muscle pain (LBPm) using nerve growth factor (NGF), a critical regulator of pain signaling and essential to muscle pain including LBPm. Repeated lumbar paraspinal intramuscular NGF injections in rats induce prolonged pain behavioral responses (e.g., paraspinal mechanical hyperalgesia) and enhanced response profiles of dorsal horn nociceptive neurons. These findings are consistent with central (spinal) sensitization, a pathophysiological state implicated in chronic pain. Central sensitization is associated with a glial cell mediated inflammatory process called neuroimmune activation, which is defined experimentally as glial cell hyperactivation with the release of proinflammatory cytokines. We hypothesized that repeated NGF paraspinal muscle injections contribute to persistent mechanical hyperalgesia and central sensitization, in part, through spinal cord neuroimmune activation. Our time course studies revealed that the development of NGF induced LBPm is associated with lumbar spinal cord dorsal horn microglial hyperactivation; suggesting that neuroimmune activation contributes to LBPm. Collectively, these models are promising and may provide a better mechanistic understanding to develop therapeutic approaches that offer meaningful LBP relief.Support or Funding InformationSLU Center for Neuroscience and NCMIC