Two to tango: GPCR oligomers and GPCR-TRP channel interactions in nociception.

G protein coupled receptors (GPCRs) represent the largest family of cell surface receptors that are involved in regulating several physiological and behavioral responses in organisms. Indeed, over half of all the approved drugs on the market target GPCRs. Over the past twenty years, several lines of evidence have suggested that GPCRs associate to form oligomeric structures that substantially expand the complexity of signaling processes in vivo. In addition, GPCRs have also been shown to functionally regulate ion channels and help fine-tune neurotransmission. In this review, we will discuss recent advances in both mechanisms, with specific focus on opioid receptors, cannabinoid receptors and transient receptor potential (TRP) calcium channels in nociception. A better understanding of such mechanisms will be imperative in designing analgesics devoid of deleterious side effects and mitigating drug abuse.