Unraveling morphine tolerance: CCL2 induces spinal cord apoptosis via inhibition of Nrf2 signaling pathway and PGC-1α-mediated mitochondrial biogenesis

Morphine effectively relieves severe pain but leads to analgesic tolerance with long-term use.The molecular mechanisms underlying morphine tolerance remain incompletely understood. Existing literature suggests that chemokine CCL2, present in the spinal cord, plays a role in central nervous system inflammation, including neuropathic pain. Nevertheless, the precise mechanism through which CCL2 mediates morphine tolerance has yet to be elucidated. Consequently, this study aims to investigate the molecular pathways by which CCL2 contributes to the development of morphine analgesic tolerance.