Electrophysiological evidence of neuronal action potential alterations by a hydroxycinnamic acid derivative at the peripheral level

Hydroxycinnamic acid derivatives have emerged as promising agents in pain management due to their multifaceted actions on various processes, including neuronal excitability. In this study, we investigated the electrophysiological effects of ferulic acid, a hydroxycinnamic acid derivative, on primary cultured dorsal root ganglion neurons using the whole-cell patch-clamp technique. Acute application of ferulic acid at a dose of 100 µM to the external solution resulted in a significant hyperpolarization of the resting membrane potential, indicating a stabilization of the neuronal membrane and a reduction in baseline excitability. Furthermore, ferulic acid induced a more negative afterhyperpolarization phase, suggesting enhanced potassium conductance and prolonged refractory periods. Notably, the threshold for action potential initiation became less negative following treatment, demonstrating that a stronger depolarizing stimulus was required to elicit neuronal firing. These changes collectively reflect a decrease in neuronal excitability that extends beyond anti-inflammatory or antioxidant effects, highlighting direct modulation of ion channel dynamics as a key mechanism. The findings provide mechanistic insight into the analgesic potential of ferulic acid by demonstrating its ability to alter action potential parameters and suppress excitability in peripheral sensory neurons. This study supports the therapeutic relevance of hydroxycinnamic acid derivatives in the development of novel analgesics targeting peripheral nociceptive pathways.