Peripheral Nerve Injury Induces Dor Trafficking To Cell Surface In Dorsal Horn Neurons

Neuropathic (NP) pain remains a significant challenge for clinicians as it is typically refractory to traditional analgesics. However, research in ours and other laboratories increasingly suggests a therapeutic role of delta opioid receptor (DOR) agonists in treating NP pain. Spinal administration of a selective DOR agonist, attenuated nerve injury‐induced allodynia and hyperalgesia with enhanced antinociceptive effects in NP rats compared with controls. This functional enhancement was not due to increased DOR biosynthesis, as DOR protein did not change. In the present study, we examined DOR subcellular localization by electron microscopy immunohistochemistry to determine whether NP injury produces a redistribution of DORs from internal stores to the cell surface. Quantification of immunopositive dendrites in the dorsal horn revealed a bilateral increase in plasma membrane‐associated DORs within lamina V neurons of NP rats compared to shams. The recruitment of DORs to neuronal plasma membranes may represent a compensatory mechanism by which neurons may sustain an inhibitory tone during chronic pain states, and in turn, indicate a viable drug target. (CIHR, J.P. Bickell Foundation, CFI/OIT, CRC)