Opioid receptors are a type of G protein-coupled receptors (GPCRs) and become activated when bound to an opioid. However, activation of the G-protein affects neurons in pain pathways by reducing excitability along the cell membranes. This is due to a reduction in cyclic adenosine monophosphate (cAMP), causing a decrease in the activity of Na􏰁 and Ca􏰁 channels and thus, resulting in analgesia. Over a span of time, changes to the receptor's G-protein mechanism can desensitize opioid receptors and reduce analgesia. This has been demonstrated in animal models where desensitization is caused by intracellular regulatory proteins or enzymes (GPCR kinases, 􏰀-arrestins, and adenylyl cyclase) that decouple opioid receptors from the G protein or "switch" coupling to a nonanalgesic G-protein which reduces analgesic activity.