Rescue of HSP70 in Spinal Neurons Alleviates Opioids-Induced Hyperalgesia via the Suppression of Endoplasmic Reticulum Stress in Rodents.

ABSTRACT: A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opioids. Endoplasmic reticulum (ER) stress has been shown to contribute to neuropathic or inflammatory pain, but its roles in opioids-induced hyperalgesia (OIH) are elusive. Here, we provide the first direct evidence that ER stress is a significant driver of OIH. GRP78, the ER stress marker, is markedly upregulated in neurons in the spinal cord after chronic morphine treatment. At the same time, morphine induces the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcripti

SUBMITTER: Lin TT 

PROVIDER: S-EPMC7243285 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature