Impact of Nav1.8 Inhibitor on Acid‑Evoked Calcium Dynamics in NGF‑Sensitized Dorsal Root Ganglion Neurons
Abstract
Pain, especially chronic pain, that affects more than 50 million Americans represents a silent public health epidemic.Lack of effective pain treatment severely impacts patients' quality of life and incurs extraordinary economic cost.Sodium channels that transmit key pain signals are promising targets for developing pain medicines.Herein, we investigated the cellular mechanism of a new sodium channel blocker targeting Nav1.8,HBW-004285, in primary cultured mouse peripheral dorsal root ganglion neurons (DRGs).We studied the effectiveness of HBW-004285 in blocking acid-triggered pain signals.Mouse DRG neurons, primed with Nerve Growth Factor (NGF) to elicit sensitization, were briefly exposed to an acidic solution.Time-lapse calcium imaging was used to monitor cellular pain activity.We showed that acid produced strong calcium surges, and NGF further sensitized the response.HBW-004285 appeared to reduce the sustained phase more than the initial peak.Furthermore, a lower dose was as effective as or outperformed a higher dose, suggesting a robust potency of HBW-004285 in blocking pain signals.Taken together, our study suggests that HBW-004285 is an effective pain blocker to support further validation and investigation of its potential therapeutical application.
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