Abstract
Persistent pain is a common symptom of both trauma and degeneration induced conditions in the spine. During both cases, the spine can undergo abnormal motions and tissue injury. Under such pathophysiological loading, peripheral and central neuroimmune and nociceptive signaling cascades are initiated that can, under certain conditions, lead to the onset and maintenance of pain. Pain sensation includes both sensory and emotional experiences, but ‘nociception’ refers to the physiological responses and signal transmission that encodes pain. Typical behavioral signs and symptoms are exhibited clinically by patients with spinal pathologies, including allodynia and hyperalgesia to mechanical and thermal stimuli. These signs are quantifiable and have been used in both clinical studies and animal models of pain, using dermatomal mapping between species.
An overview of the anatomy and physiology of spinal tissues with the potential for pain generation will be reviewed, together with the relationships between tissue loading, nociceptive signaling and pain. These will be addressed from macroscopic points of view to cellular injuries, and incorporating both neuronal and associated immune and other physiological cascades which can complicate the pain response. Building off of that work, findings from in vivo models will be reviewed, particularly those that incorporate methods to understand the spatio-temporal mechanisms of pain production, both at the site of pain origin and in the central nervous system (CNS). Findings regarding pain symptoms will be related to the physiological cascades in both the periphery and the central nervous system. Nociceptive signaling can lead to sensitization, which is increased responsiveness of neurons to their normal input or recruitment of a response to normally subthreshold inputs. Sensitization can occur in the periphery or in the CNS. Peripheral sensitization leads to altered nociceptive responses at the injury site, including decreased thresholds for afferent firing and increased responsiveness of peripheral nociceptive neurons; central sensitization involves the increased spontaneous activity and responsiveness of nociceptive neurons in the CNS, which results in increased nociception at secondary sites that have no tissue damage. These will be reviewed in the context of our models of neuropathic and ligament based pain in the rat. Given the challenges in measuring ligament damage other than gross tissue responses in vivo, we separately present studies that further investigate local mechanotransduction processes by highlighting relationships between locally-induced biomechanical deformations and microstructural changes, and the release of pain mediators. Lastly, early findings related to measuring the affective components of pain in the rat, along with work highlighting the importance of some of these findings for pain therapies and interventions that specifically target those spatiotemporal neuroimmune cascades will be presented to provide context for the other presentations.
This work was funded by the Centers for Disease Control, the National Science Foundation, NIH, NHTSA, Department of Defense, and the Catharine Sharpe Foundation.
Disclosures: None