Figure 5.

Inhibition of Cav3.2 in sensory neurons underlies NAGly-induced analgesia. A, B, Calcium currents recorded (in the absence of sodium) from DRG neurons in the absence (Ctrl) and presence of 3 μm NAGly and after washout with a solution containing 3 mg/ml BSA. Currents were elicited by a depolarization (200 ms) at −30 mV (A, T-type) or at 0 mV (B, HVA) applied every 5 s from −75 mV. C, D, Effects of NAGly on sodium currents in DRG neurons. Sodium currents were recorded in the presence of 10 μm La³⁺ (a calcium channel blocker) with [D, I(Na) TTX-r] or without [C, I(Na) total] 0.5 μm TTX. Currents were elicited by a depolarization at 0 mV (20 ms duration) applied every 5 s from −70 mV (C) or −50 mV (D). E, Summary of the effects of NAGly on calcium and sodium currents in DRG neurons (n = 10–12). To limit the contamination of T-currents by HVA currents, and vice versa, HVA currents were measured as the remaining current after 150 ms, whereas T-currents were measured as the difference between the peak current and the remaining current after 150 ms. F, G, Effects of vehicle and NAGly solution on thermal pain (46°C) when injected in the hindpaw in WT (F) and Cav3.2 KO mice (G). Results are expressed as the PWL as a function of the time after injection. The “Pre” values represent the values obtained before injection. H, Summary of the data obtained in WT mice 10 min after injection of vehicle, BSA, NAGly, NAGABA-OH, and morphine (n = 8–10 mice per bars). Effect of NAGABA-OH on PWL in contralateral (contra.) is also reported in WT mice (n = 9). I, J, Effects of vehicle and NAGABA-OH solution on thermal pain (46°C) when injected in the hindpaw in WT (I) and Cav3.2 KO mice (J). Effect of NAGABA-OH on PWL in contralateral is also reported for WT mice as indicated (I). K, Summary of the data obtained in Cav3.2 KO mice 10 min after injection of vehicle, BSA, NAGly, NAGABA-OH, and morphine (n = 8–10 mice per bars).