Neuropathic pain after spinal cord injury: Mechanisms, animal models and pain assessments.

Abstract

Neuropathic pain after spinal cord injury (SCI-NP) often has lifelong and significant negative effects. Therefore, understanding its underlying mechanisms is a current research priority. SCI-NP involves central sensitization, neuroinflammation and functional remodeling in the brain, hyperexcitability of primary sensory neurons, and peripheral-central interactions. The mechanism of SCI-NP at the spinal cord level is an important one to study. Glial cell activation and proinflammatory pathways in the spinal cord are the key drivers that lead to central sensitization at the spinal cord level, and they constitute the main mechanisms of current research. However, the mechanism of SCI-NP remains unclear, mainly because of the lack of standardized and uniform animal models in preclinical studies. Animal models provide a basis for the mechanistic study of SCI-NP, but the stability and repeatability of these models pose problems. Behavioral evaluation of animal models of SCI-NP has focused on mechanical and heat-induced pain thresholds, but this phenotype is different from the clinical diagnostic criteria of SCI-NP in patients, which includes at least four positive signs according to the DN4 scale. Electrophysiological recordings, especially from spinal dorsal horn neurons and dorsal root ganglia neurons, provide important support for SCI-NP research. In summary, the development of SCI-NP involves a complex pathological process, and its mechanisms remain incompletely understood. Existing models and detection methods require refinement. This review focuses on the research progress in this field and looks forward to future research directions.