Figure 2.
Schematic drawing showing the site and effectors of GPCRs in the modulation of pain transmission at the spinal cord level. Activation of GPCRs listed on the left inhibits VGCCs on the presynaptic terminal of primary afferents to reduce glutamate release. These GPCRs also activate GIRK channels on postsynaptic dorsal horn neurons to hyperpolarize the neuron. Additionally, stimulation of mAChRs potentiates the synaptic release of GABA and glycine from inhibitory interneurons to decrease the excitability of dorsal horn neurons that project to the brain. Together, these effects account for the analgesic effects of the agonists of these GPCRs. GIRK, G protein-coupled inwardly rectifying K+ channels; GPCRs, G protein-coupled receptors; mAChRs, muscarinic acetylcholine receptors; mGluRs, metabotropic glutamate receptors; VGCCs, voltage-gated Ca2+ channels.