Objectives: The knowledge about the molecular pathway of traumatic pain relief is less documented. This systematic review study aimed to identify the genes and molecular pathways associated with various traumatic pains. Methods: The online databases such as EMBASE, MEDLINE, PubMed, Cochrane Library, International Clinical Trials Registry Platform, Clinical Trials, Google Scholar, Wiley, ISI Web of Knowledge, and Scopus were searched. Two review authors searched and screened all records' titles and abstracts, and the third expert reviewer author resolved their disagreement. The study’s design, various trauma injuries, types of genes, and molecular pathways were recorded. The genes and molecular pathways data were obtained via GeneCards?: The Human Gene Database (https://www.genecards.org). Results: Studies on a variety of trauma injuries regarding nerve and Spinal Cord Injuries (SCIs) (12 records), Hypertrophic scar with Severe Pain (one record), severe post-traumatic musculoskeletal pain (MSP) (one record), and orthopedic trauma (one record) were included. The main molecular pathways such as the immune system, apoptosis, and death receptor signaling, T-cell antigen receptor (TCR) signaling pathway, oxidative stress, interleukin(s) mediated signaling pathway, biological oxidations, metabolic pathways (especially amino acid metabolism and amino group), focal adhesion, the proliferation of vascular, epithelial, and connective tissue cells, angiogenesis and neural development were identified. Conclusion: The immune system, apoptosis, and metabolic pathways are crucial for understanding the roles of genes in traumatic pain. It is recommended that these identified pathways and related genes be considered therapeutical targets for pain management in patients with trauma injuries. In addition, different forms of trauma injuries require different pathways and related genes to be considered.
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