Anti–PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates
Zilong Wang, Changyu Jiang, Qianru He, Megumi Matsuda, Qingjian Han, Kaiyuan Wang, Sangsu Bang, Huiping Ding, Mei‐Chuan Ko, Ru‐Rong Ji
Abstract
mice. MOR and PD-1 are coexpressed in sensory neurons and their axons in mouse and human DRG tissues. Morphine produced antinociception by (i) suppressing calcium currents in DRG neurons, (ii) suppressing excitatory synaptic transmission, and (iii) inducing outward currents in spinal cord neurons; all of these actions were impaired by PD-1 blockade in mice. Loss of PD-1 also enhanced opioid-induced hyperalgesia and tolerance and potentiates opioid-induced microgliosis and long-term potentiation in the spinal cord in mice. Last, intrathecal infusion of nivolumab inhibited intrathecal morphine-induced antinociception in nonhuman primates. Our findings demonstrate that PD-1 regulates opioid receptor signaling in nociceptive neurons, leading to altered opioid-induced antinociception in rodents and nonhuman primates.