Therapeutic Strategies for Neuropathic Pain: Potential Application of Pharmacosynthetics and Optogenetics

Figure 1

Illustration of molecular changes contributing to neuropathic pain in nociceptive fiber and potential strategy to suppress the hyperexcitability. Following nerve lesion or inflammation in nociceptive fiber, nociceptive sensory afferent undergoes chronic alteration in expression profiles of membrane proteins. Inflammatory mediators secreted from activated immune cells can initiate transcriptional remodeling on DRG nociceptors by acting on G protein-coupled receptors (GPCRs). Alterations of nociceptor membranes in neuropathic pain development involve upregulation of several subtypes of voltage-gated sodium channels and downregulation of membrane stabilizing voltage-gated potassium channels. These alterations on the excitable membrane lead to the exaggerated action potential propagation in response to subnoxious stimuli, ultimately transmitting neuropathic pain perception in higher brain structure. The abnormal action potential firing in neuropathic pain-inflicted DRG could be suppressed via expression of halorhodopsin or inhibitory G protein-coupled DREADDs, both of which can stabilize membrane potentials. Application of light or CNO for these types of membrane proteins could provide opportunity to control neuropathic pain transmission immediately.