Opioidsystem

Opioidsystem, or the endogenous opioid system, refers to a set of neurochemical signaling pathways that regulate pain, reward, stress, and homeostasis. It comprises endogenous opioid peptides, their receptors, and the neural circuits in which they act. The primary receptors are μ (mu), δ (delta), and κ (kappa) opioid receptors, with a related receptor called the nociceptin/orphanin FQ receptor (NOP). Endogenous ligands include beta-endorphin (POMC-derived), enkephalins (proenkephalin-derived), and dynorphins (prodynorphin-derived). Binding to these receptors inhibits adenylyl cyclase, reduces Ca2+ influx, and activates potassium channels, producing inhibitory effects on neuronal excitability.

Functions: The opioid system modulates nociceptive signaling at both spinal and supraspinal levels, contributing to analgesia. It also influences reward, mood, and stress responses, and can regulate gastrointestinal motility and immune function. The system participates in placebo analgesia and in learning and memory related to pain and relief.

Clinical relevance: Exogenous opioids, such as morphine, fentanyl, and oxycodone, primarily target μ receptors and provide potent analgesia but carry risks of tolerance, physical dependence, and respiratory depression. Dysregulation of the system is associated with opioid use disorder and overdose. Peripherally restricted opioids and biased agonists are areas of research aimed at providing analgesia with fewer central side effects.