Insights into ion channels to identify drug target for neuropathic pain management

Neuropathic pain (NP) is a debilitating condition resulting from maladaptive changes in the nervous system, characterised by heightened neuronal excitability and persistent pain. Despite the availability of symptomatic treatments, effective long-term relief remains elusive due to an incomplete understanding of its underlying mechanisms. Ion channels play a pivotal role in regulating neuronal excitability and pain transmission, yet remain underexploited in drug discovery. This review explores the structural and functional dynamics of key ion channels, including voltage-gated sodium (VGSCs), hyperpolarisation-activated cyclic nucleotide-gated (HCN), transient receptor potential vanilloid-1 (TRPV1), and potassium channels, highlighting their contributions to NP and therapeutic potential. We evaluate current modulators, recent clinical advancements, and the challenges of targeting these channels selectively. A deeper understanding of these molecular mechanisms can guide the development of next-generation non-opioid analgesics. This integrative review underscores the potential of ion channels as emerging targets for mechanism-based NP management.