Recent studies implicate melatonin in the antinociceptive activity of sensory neurons. However， the underlying mechanisms are still largely unknown. Here， we identify a critical role of melatonin in functionally regulating Cav3.2 T-type Ca channels (T-type channel) in trigeminal ganglion (TG) neurons. Melatonin inhibited T-type channels in small TG neurons via the melatonin receptor 2 (MT receptor) and a pertussis toxin-sensitive G-protein pathway. Immunoprecipitation analyses revealed that the intracellular subunit of the MT receptor coprecipitated with Gα . Both shRNA-mediated knockdown of Gα and intracellular application of QEHA peptide abolished the inhibitory effects of melatonin. Protein kinase C (PKC) antagonists abolished the melatonin-induced T-type channel response， whereas inhibition of conventional PKC isoforms elicited no effect. Furthermore， application of melatonin increased membrane abundance of PKC-eta (PKC ) while antagonism of PKC or shRNA targeting PKC prevented the melatonin-mediated effects. In a heterologous expression system， activation of MT receptor strongly inhibited Cav3.2 T-type channel currents but had no effect on Cav3.1 and Cav3.3 current amplitudes. The selective Cav3.2 response was PKC dependent and was accompanied by a negative shift in the steady-state inactivation curve. Furthermore， melatonin decreased the action potential firing rate of small TG neurons and attenuated the mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain. These actions were inhibited by T-type channel blockade. Together， our results demonstrated that melatonin inhibits Cav3.2 T-type channel activity through the MT receptor coupled to novel G -mediated PKC signaling， subsequently decreasing the membrane excitability of TG neurons and pain hypersensitivity in mice.