Opioids modulate nociception in the terminals of afferent nerves in the central nervous system (CNS), peripheral nervous system, and gastrointestinal tract. They are agonists at the mu1, mu2, kappa, delta, sigma, and epsilon receptors in these tissues. The opioids with a preference for the mu receptors are the more potent analgesics, but delta and kappa agonists are effective analgesics as well. 1 Opioids bind to the receptor sites and either decrease neurotransmitter release or open potassium channels, resulting in hyperpolarization of the neuronal membranes. Specific binding at different receptor sites located within the locus ceruleus activate the "pleasure pathway" and result in dependence and craving. The endogenous opioids—enkephalins, endorphins, and dynorphins—are the natural ligands at all the receptor sites mentioned above.

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