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During the 7-day treatment schedule, MP-13 maintained stable antinociception without tolerance development, as evidenced by the unchanged microglial cell count in the periaqueductal gray, indicating that chronic exposure did not trigger neuroinflammatory adaptationa process in which microglia become activated, release pro-inflammatory cytokines, and contribute to opioid tolerance

Carabao MJ, Ramn M, Menndez-Buxadera A, Molina A, Daz C (2019) Selecting for heat tolerance