Figure 1.

Suppression of sodium currents by opioid analgesics in rat thalamic neuron through non-opioidergic mechanisms. Voltage steps were applied from a holding potential of −70 mV to a test potential of −20 mV. (A) Representative current traces obtained in the presence or absence of 100 μM morphine, fentanyl or oxycodone. (B) Concentration-dependent inhibition of the sodium currents by morphine, fentanyl, oxycodone and lidocaine in rat cultured thalamic neurons. Each symbol represents the mean value of normalized peak currents in the presence of drug (I/I_o, mean ± S.E.M.), derived from 3-8 independent experiments for each concentration tested. (C) No effects of the opioid receptor antagonist naloxone (10 μM) on suppression of sodium currents by the bath application of 100 μM morphine, fentanyl or oxycodone. (D) No involvement of MORs in fentanyl-induced suppression of sodium currents in thalamic neurons using MOR^−/− mice. Each column represents the normalized peak current amplitudes (I/I₀, mean ± S.E.M., n = 5). ***p<0.001 control (WT) vs. fentanyl (WT), ##p<0.01 fentanyl (WT) vs. washout (WT), †††p<0.001 control (MOR^−/−) vs. fentanyl (MOR^−/−), ƒƒp<0.01 fentanyl (MOR^−/−) vs. washout (MOR^−/−). (E) Effects of endogenous μ-opioid peptides on voltage-gated sodium channels in rat cultured thalamic neurons. No significant changes in sodium currents were observed with the bath application of 1-100 μM β-endorphin (n = 5-7), endomorphin-1 (n = 3) or endomorphin-2 (n = 3-8). Each column represents the mean value of the % inhibition of the peak amplitude of the sodium currents in the presence of drug (mean ± S.E.M.).