Cholesterol metabolism and neuroinflammatory changes in a non-human primate spinal nerve ligation model.

Neuropathic pain remains one of the major neurological conditions with high unmet medical needs. Poor translation from preclinical studies using rodent models to clinical trials is one of the major obstacles to the development of new pharmacological medications to treat neuropathic pain. The aims of this study were to establish a behavioral test to evaluate spontaneous pain in a spinal nerve ligation (SNL) model using cynomolgus monkey as a non-human primate (NHP) model. After right unilateral L7 SNL surgery in cynomolgus monkeys, the percentage of weight-bearing on ipsilateral hindlimb significantly decreased, which was well-associated with an analytical score of electroencephalography (EEG). Transcriptomic analysis of RNA-seq results from the dorsal part of the spinal cord identified pathways matching those in equivalent rodent models, along with NHP-specific pathways, suggesting that neuroinflammation and cholesterol transportation/metabolism were the main pathways altered in this NHP model. Additionally, several upregulated genes observed here were previously reported uniquely in clinical studies, but not in rodent models. This study provides a potentially useful model that can aid our understanding of pathophysiological mechanism of neuropathic pain and the development of pain relief therapies by inducing a robust behavioral phenotype and changes in gene expression resembling those in patients.