Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons

Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1 mmol⋅L−1) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2 mmol⋅L−1 CGA decreased the peak current density of IK,A. Both 0.2 mmol⋅L−1 and 1 mmol⋅L−1 CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects. A plant-derived compound with therapeutic potential may inhibit pain signals through its effects on specific nerve cell proteins. Scientists have recently begun exploring the anti-cancer, anti-inflammatory and neurological effects of chlorogenic acid (CGA), a molecule produced by bamboo and other plants. Jie-Fei Shen and colleagues at Sichuan University in China examined the effects of CGA on two ‘potassium-gated voltage channel’ (KV) proteins, which participate in nerve cell signaling. The researchers examined cells from the rat trigeminal ganglion, a nervous system structure that detects and responds to pain. CGA increased the activity of both KV proteins, and Shen and colleagues predict that the resulting response would gradually dampen trigeminal pain signaling. These findings could assist the development of drugs that block the severe discomfort associated with inflammatory and neuropathic pain.