Cumulating evidence indicated that nerve injury-associated cellular and molecular changes play an essential role in contributing to the development of pathological pain, and more recent findings implicated the critical role of epigenetic mechanisms in pain-related sensitization in the DRG subsequent to nerve injury. In this part of the dyad review (Part II), we reviewed and paid special attention on the etiological contribution of DGR gene expression modulated by epigenetic mechanisms of CRPS. As essential effectors to different molecular activation, we first discussed the activation of various signaling pathways that subsequently from nerve injury, and in further illustrated the fundamental and functional underpinnings of nerve injury-induced pain, in which we argued for the potential epigenetic mechanisms in response to sensitizing stimuli or injury. Therefore, understanding the specific mediating factors that influence individual epigenetic differences contributing to pain sensitivity and responsiveness to analgesics possesses crucial clinical implications.

Keywords: Complex Regional Pain Syndromes - etiology, Brain-Derived Neurotrophic Factor - metabolism, Epigenesis, Genetic - physiology, Ganglia, Spinal - metabolism, Gene Expression Regulation - physiology, Oxytocin - metabolism, Protein Kinases - metabolism, Receptors, G-Protein-Coupled - metabolism, Signal Transduction - physiology, Transcription Factors - metabolism, Trauma, Nervous System - complications