Transcriptomic mechanisms of lumbar sympathectomy improving cold allodynia of nerve injury in rat

BACKGROUND: Neuropathic Pain (NP) is a chronic pain caused by damage to the nervous system, often manifested as spontaneous pain, pain allergy and abnormal pain. Cold abnormal pain is one of the common manifestations of neuropathic pain, which seriously affects the quality of life of patients. Lumbar sympathetic nerve resection has been widely used to treat lower limb pain, but its specific mechanism in cold abnormal pain is not yet clear. MATERIALS: A chronic constriction injury (CCI) of the sciatic nerve model and a lumbar sympathectomy (LS) model were established to investigate the effect of LS on abnormal cold pain in CCI rats and its molecular mechanism. The effect of LS on cold allodynia in CCI rats was observed through behavioral tests, including the measurement of mechanical pain threshold, the acetone cold stimulation test, and the cold plate test. The changes in the levels of differentially expressed genes in CCI rats after LS were further observed by transcriptome sequencing (bulk RNA-seq). RESULT: Through behavioural experiments and transcriptome sequencing (bulk RNA-Seq) analysis, we found that lumbar sympathectomy (LS) significantly alleviated cold allodynia, cold-evoked allodynia and cold pain sensitivity in CCI rats, and changed the spinal cord transcriptome, including pathways related to inflammatory signal transduction and tissue remodelling. The functional enrichment analysis of differential expression genes (DEGs) revealed a number of signalling pathways associated with pain regulation. This study provides a new molecular biological basis for the application of LS in alleviating cold abnormal pain.