Pain Men and women experience pain differently, but the mechanisms mediating this difference and their universality, are unclear. In female rodents, the short isoform of the prolactin receptor (PRLR-S), but not the long isoform (PRLR-L), has been shown to regulate the excitability of sensory neurons. Chen et al. studied opioid-induced hyperalgesia (OIH) in a mouse model and found that opioid administration, but not trauma-induced nerve injury, augmented prolactin and decreased PRLR-L in female mice, promoting the activation of PRLR-S and the development of OIH. Prolactin inhibition prevented the occurrence of OIH in female mice, and targeting prolactin signaling is an attractive direction for future research in preventing OIH in women. Sci. Transl. Med. 12 , eaay7550 (2020).