Phosphatase of regenerating liver-1 is associated with inflammatory pain, spinal GluN2B upregulation, and microglial activation.

Central sensitization in the spinal dorsal horn, characterized by enhanced neuronal excitability and sustained neuroinflammatory responses, is a key mechanism underlying persistent inflammatory pain; however, the upstream molecular regulators coordinating these processes remain incompletely understood. In this study, a mouse model of inflammatory pain was established by intraplantar injection of complete Freund's adjuvant (CFA), and lentiviral short hairpin RNA was used to knock down phosphatase of regenerating liver-1 (PRL-1) in the spinal dorsal horn. CFA-induced inflammatory pain was associated with persistent mechanical hypersensitivity and increased PRL-1 expression in spinal neurons. PRL-1 knockdown attenuated pain hypersensitivity and was accompanied by reduced expression of the N-methyl-D-aspartate receptor subunit GluN2B. In addition, PRL-1 knockdown was associated with decreased microglial reactivity and lower levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Together, these findings suggest that PRL-1 is associated with inflammatory pain and spinal neuronal sensitization and neuroinflammatory responses.