Plant-derived natural products targeting ion channels for pain

Chronic pain affects approximately one-fifth of people worldwide and reduces quality of life and in some cases, working ability. Ion channels expressed along nociceptive pathways affect neuronal excitability and as a result modulate pain experience. Several ion channels have been identified and investigated as potential targets for new medicines for the treatment of a variety of human diseases, including chronic pain. Voltage-gated channels Na⁺ and Ca²⁺ channels, K⁺ channels, transient receptor potential channels (TRP), purinergic (P2X) channels and acid-sensing ion channels (ASICs) are some examples of ion channels exhibiting altered function or expression in different chronic pain states. Pharmacological approaches are being developed to mitigate dysregulation of these channels as potential treatment options. Since natural compounds of plant origin exert promising biological and pharmacological properties and are believed to possess less adverse effects compared to synthetic drugs, they have been widely studied as treatments for chronic pain for their ability to alter the functional activity of ion channels. A literature review was conducted using Medline, Google Scholar and PubMed, resulted in listing 79 natural compounds/extracts that are reported to interact with ion channels as part of their analgesic mechanism of action. Most in vitro studies utilized electrophysiological techniques to study the effect of natural compounds on ion channels using primary cultures of dorsal root ganglia (DRG) neurons. In vivo studies concentrated on different pain models and were conducted mainly in mice and rats. Proceeding into clinical trials will require further study to develop new, potent and specific ion channel modulators of plant origin.