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Prior restraint stress (RS) increased the magnitude and duration of incisional injury\u2013induced postoperative pain hypersensitivity in both male and female mice. In females, RS or incisional injury downregulated PRLR-L and increased PRL-dependent nociceptor excitability. Female selective inhibition of postoperative pain hypersensitivity was produced by a) pharmacological inhibition of pituitary PRL b) overexpression of DRG PRLR-L to bias PRL signaling away from PRLR-S and c) CRISPR\/Cas9 editing of PRLR isoforms. PL200,019, our recently discovered monoclonal antibody against human PRL (hPRL), prevented hPRL-induced sensitization of human female nociceptors. Using female mice genetically modified to express hPRL, rather than murine PRL, PL200,019 prevented both stress and incisional injury\u2013induced hypersensitivity. 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