The activation of ion channels at the peripheral terminals in response to unpleasant stimuli causes membrane depolarization and the generation of action potentials in afferent fibers. These action potentials are generated by ion channel activation and propagate along axons to postsynaptic nerve terminals in the spinal dorsal horn. TMEM16 Transmembrane protein 16 (Anoctamins), TRPV Transient Receptor Potential Vanilloid, TRPA1 Transient Receptor Potential Ankyrin 1, TRPM8 Transient Receptor Potential Melastatin 8, ASIC Acid-Sensing Ion Channel, VGCC Voltage-dependent Calcium Channel, VGKC Voltage-Gated Potassium Channel, VGSC Voltage-Gated Sodium Channel, HCN Hyperpolarization-activated, and Cyclic Nucleotide-gated channel [10,12,13].