Opioids bind to the G protein of the opioid receptors, which are widespread in the central nervous system, the peripheral nervous system, and other tissues. The sites in the central nervous system are associated with the processing of the affective and suffering aspects of pain perception. These include the cortex, central gray medial thalamus, amygdala, limbic cortex, midbrain, and spinal cord. It appears that opioids are not concentrated on the somatosen-sory cortex, which is important for pain localization. Sites in the peripheral nervous system include the mesenteric plexus of the gastrointestinal tract and the afferent neurons. Sites in other tissues include the lung and the joints. The presynaptic receptors are both excitatory and inhibitory, while the postsynaptic receptors are only inhibitory (Crain and Shen 1990). Opioids can bind to both the presynaptic and postsynaptic receptors. Presynaptic binding of the opioid receptors by opioids decreases adenylate cyclase activity, inhibits calcium channels that are voltage sensitive, and decreases the release of neurotransmitters such as glutamate, serotonin, norepinephrine, acetylcholine, and substance P (Herz 1993). The binding of the opioid receptors to the postsynaptic receptors leads to an increase in the outward conductance of potassium, hyperpolarization, and a corresponding decrease in neural transmission.
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