Neuron Modulation by Synergetic Management of Redox Status and Oxidative Stress

The transient receptor potential (TRP) channel is a key sensor for diverse cellular stimuli, regulating the excitability of primary nociceptive neurons. Sensitization of the TRP channel can heighten pain sensitivity to innocuous or mildly noxious stimuli. Here, reversible modulation of TRP channels is achieved by controlling both the light-induced photoelectrochemical reaction to induce neuronal depolarization, and antioxidants for neuronal protection. It is based on a hybrid nanosystem, CZPN, created by coating CeO₂ nanocrystals with the metalloporphyrin ZnTPyP. Light irradiation triggers an electrochemical response, with efficient electron injection from ZnTPyP to CeO₂, converting Ce⁴⁺ into Ce³⁺ as antioxidants. Meanwhile, the charge migrates from surrounding O₂ molecules to the hole-injected ZnTPyP^*, giving rise to reactive oxygen species (ROS). This change in the redox environment sensitizes TRP channels, eliciting action potentials in primary rat neurons, and is partially blocked by pretreatment with capsazepine. The resulting CeO_2-x, with a high Ce³⁺/Ce⁴⁺ ratio, can scavenge excessive ROS to prevent oxidative damage. The light-induced pain behaviors in mice pre-injected with CZPN are further confirmed. This work suggests a safe, effective, and universal approach to photoelectrochemical processes for modulation and research of the peripheral nervous system.