The mu-opioid receptor agonists have a preferential effect on nociception in adults but their analgesic effect is less selective in neonates. Here we presented our finding that the mu-opioid receptor agonists had no effect on high voltage-activated Ca(2+) channels (HVACCs) in adult dorsal root ganglion (DRG) neurons that exhibited a prominent T-type Ca(2+) current. We also determined the mechanisms underlying the mu-opioid agonists' lack of effect on HVACCs in these neurons. The mu-opioid agonist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO), morphine, and morphine 6-beta-D-glucuronide had no effect on either T-type or HVACC currents despite the presence of a large N-type Ca(2+) current in neurons with T-type Ca(2+) currents. DAMGO still had no effect on HVACC currents when T-type Ca(2+) channels were blocked in these neurons. However, intracellular dialysis of GTP-gamma-S to activate G proteins significantly attenuated HVACC currents. DRG neurons with T-type Ca(2+) currents showed little responses to capsaicin. Single-cell RT-PCR analysis revealed that the mu-opioid receptor mRNA was present only in adult DRG neurons lacking prominent T-type Ca(2+) currents. In the neonatal DRG, DAMGO inhibited HVACC currents in 31% neurons with T-type Ca(2+) currents. The mu-opioid receptor mRNA was detected in all neurons without T-type Ca(2+) currents and also in 28.6% of neurons with T-type Ca(2+) currents in the neonatal DRG. Our study provides novel information that adult DRG neurons with prominent T-type Ca(2+) currents do not express mu-opioid receptors. Expression of T-type Ca(2+) (Ca(V)3.2) channels and mu-opioid receptors may be developmentally co-regulated as some DRG neurons differentiate toward becoming nociceptive neurons.