Ion Channels and G-Protein-Coupled Receptors Involved in the Development of Chronic Post-ischemic Pain (CPIP): A Model of Complex Regional Pain Syndrome (CRPS-I).

Chronic pain is a physical and emotional sensation that exceeds biological necessity. Complex regional pain syndrome (CRPS) is considered a chronic primary pain condition that can arise after limb trauma, such as surgery, ischemia, and fractures. This type of pain is a multifactorial disorder that predominantly affects one body extremity and occurs either without initial nerve injury (CRPS-I) or with partial or complete nerve injury (CRPS-II). Therefore, CRPS-I is still a painful and debilitating condition without a complete understanding of its underlying mechanisms. This gap in knowledge about CRPS-I pathophysiology contributes to patient suffering, as there is still no standard pharmacological treatment. Preclinical research uses diverse models of CRPS-I, such as chronic post-ischemia pain (CPIP), to better understand its pain activation pathways. Various mechanisms continue to emerge in CPIP, including the role of different G-protein-coupled receptors (GPCRs) and ion channels. In this review, we will focus on the mechanisms surrounding these different GPCRs and ion channels in a model of CRPS-I-induced nociception in rodents (the CPIP model). To date, the primary targets studied in CPIP pathophysiology include transient receptor potential (TRP) and N-methyl-D-aspartate (NMDA) ion channels, as well as cannabinoid, bradykinin, adenosine, adrenergic, and endothelin GPCRs.