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Pain is an essential protective mechanism that the body uses to alert or prevent further damage. Pain sensation is a complex event involving perception, transmission, processing, and response. Neurons at different levels (peripheral, spinal cord, and brain) are responsible for these pro- or antinociceptive activities to ensure an appropriate response to external stimuli. The terminals of these neurons, both in the peripheral endings and in the synapses, are equipped with G protein-coupled receptors (GPCRs), voltage- and ligand-gated ion