Abstract

The gaseous signaling molecule carbon monoxide (CO) is increasingly recognized as a critical modulator of neuronal function, yet its role in sensory transduction pathways remains poorly understood. This study investigates the effect of CO on adenosine triphosphate (ATP)-evoked activity in rat trigeminal afferent neurons, which are central to nociception and craniofacial sensation. Using whole-cell patch-clamp electrophysiology on isolated trigeminal ganglion neurons, we characterized the purinergic currents activated by exogenous ATP. Co-application of a CO-releasing molecule significantly and concentration-dependently inhibited the amplitude of the ATP-evoked inward currents. Further analysis revealed that CO did not alter the reversal potential but significantly accelerated the desensitization rate of the P2X receptor-mediated currents, suggesting a non-competitive mechanism of action. These findings indicate that CO acts as an endogenous negative regulator of purinergic signaling in trigeminal afferents, potentially by allosterically modifying the P2X receptor complex or downstream membrane-associated signaling molecules. This novel modulatory pathway highlights a mechanism by which CO may contribute to the peripheral regulation of pain and inflammatory signaling, offering a new therapeutic target for trigeminal neuralgia and other sensory disorders.