Redox-dependent activation of protein kinase G1α contributes to transient receptor potential cation channel subfamily V member 1-mediated acute nociceptive pain behavior.

Background: Sensory neurons relay the pain signals to the brain via the nociceptive system. Notably, reactive oxygen species (ROS) serve as signaling molecules in the somatosensory system; however, their contribution to sensing noxious stimuli remains poorly understood.

Methods: Herein, the role of protein kinase G (PKG)1α, which is highly expressed in sensory neurons and serves as a ROS target, was investigated in sensory neurons in the processing of acute nociceptive pain. Cys42Ser PKG1α-knock-in (PKG1α-KI) mice, devoid of redox-dependent PKG1α activation, were subjected to behavioral testing, ROS detection assays, gene expression experiments, and imaging analyses.

Results: Interestingly, PKG1α-KI mice showed reduced behavioral responses to noxious heat and the transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist capsaicin. Moreover, capsaicin-induced sensory neuron stimulation upregulated ROS production and redox-dependent PKG1α activation. Calcium imaging results and patch-clamp recordings revealed that capsaicin-induced calcium flux and neuronal excitability was reduced in sensory neurons of PKG1α-KI mice.

Conclusion: Altogether, the findings of this study show the effects of redox-dependent PKG1α activation on capsaicin/TRPV1-mediated signaling in sensory neurons during acute nociceptive pain.