Pellino1 Contributes to Morphine Tolerance by Microglia Activation via MAPK Signaling in the Spinal Cord of Mice.

ABSTRACT: Chronic morphine-induced antinociceptive tolerance is a major unresolved issue in clinical practices, which is associated with microglia activation in the spinal cord. E3 ubiquitin ligase Pellino1 (Peli1) is known to be an important microglia-specific regulator. However, it is unclear whether Peli1 is involved in morphine tolerance. Here, we found that Peli1 levels in the spinal cord were significantly elevated in morphine tolerance mouse model. Notably, Peli1 was expressed in a great majority of microglia in the spinal dorsal horn, while downregulation of spinal Peli1 attenuated the development of morphine tolerance and associated hyperalgesia. Our biochemical data revealed that morphine tolerance-induced increase in Peli1 was accompanied by spinal microglia activation, activation of mito

SUBMITTER: Wang L 

PROVIDER: S-EPMC11448779 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature