Ion Channel Genes in Painful Neuropathies

Abstract

Neuropathic pain (NP) is a typical symptom of peripheral nerve disorders, including painful neuropathy. The biological mechanisms that control ion channels are important for many cell activities and are also therapeutic targets. Disruption of the cellular mechanisms that govern ion channel activity can contribute to pain pathophysiology. The voltage-gated sodium channel (VGSC) is the most researched ion channel in terms of NP; however, VGSC impairment is detected in only <20% of painful neuropathy patients. Here, we discuss the potential role of the other peripheral ion channels involved in sensory signaling (transient receptor potential cation channels), neuronal excitation regulation (potassium channels), involuntary action potential generation (hyperpolarization-activated cyclic nucleotide-gated channels), thermal pain (anoctamins), pH modulation (acid sensing ion channels), and neurotransmitter release (calcium channels) related to pain and their prospective role as therapeutic targets for painful neuropathy.

Keywords: channelopathies; ion channel genes; neuropathic pain; neuropathy; pathophysiology; variants.

Figure 1

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].