Interaction and regulatory functions of μ- and δ-opioid receptors in nociceptive afferent neurons.

μ-opioid receptor (MOR) agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and dependence. Earlier studies reported that MOR analgesic tolerance is reduced by blockade of δ-opioid receptors (DORs) that interact with MORs. Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance. Further analysis of the mechanisms for regulating the trafficking of receptors, ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.