Delta Opioid Receptors Presynaptically Regulate Cutaneous Mechanosensory Neuron Input to the Spinal Cord Dorsal Horn

The study revealed that delta opioid receptors (DOR) played a crucial role in regulating cutaneous mechanosensation, including touch, by inhibiting synaptic input to the spinal dorsal horn through blocking voltage-gated calcium channels. DOR was primarily expressed in large-diameter, myelinated mechanoreceptors, challenging previous beliefs about its expression in small-diameter neurons. The research used a DORGFP knockin mouse model to map DOR distribution and found that DOR agonists like deltorphin II significantly reduced neurotransmitter release, suggesting a potential target for treating injury-induced mechanical hypersensitivity. The study highlighted the distinct roles of DOR and mu opioid receptors (MOR) in somatosensory processing, with DOR affecting mechanoreceptors involved in touch sensation and MOR associated with nociceptive pathways. These findings provided insights into the molecular mechanisms by which opioids could modulate touch and pain sensations.