Targeting NFAT5 alleviated CCI‐induced neuropathic pain. A1‐A3) Behavioral tests of paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), and spontaneous pain scores after CCI surgery. ***p < 0.001, n = 8, two‐way ANOVA with repeated measures followed by Tukey's multiple comparison test. B1‐B3) NFAT5 protein level in the injured ipsilateral spinal dorsal horn (SDH) and ipsilateral L4‐L5 DRG after sham or CCI surgery. *p < 0.05, **p < 0.01, n = 6, one‐way ANOVA followed by Tukey's multiple comparison test. C1) Validation of knockdown efficiency after intrathecal (i.t.) injection of AAV2/9‐shNfat5 in rats SDH. *p < 0.05, n = 6, two‐tailed unpaired student's t‐test. C2‐C3) Rats were i.t. injection of AAV2/9‐shNfat5 for 2 weeks followed by CCI modeling and then performed PWMT and PWTL pain behavioral tests. CCI + AAV2/9‐shNfat5 versus CCI + AAV2/9‐NC, *p < 0.05, **p < 0.01, ***p < 0.001, n = 8, two‐way ANOVA with repeated measures followed by Tukey's multiple comparison test. D1‐D3) Behavioral tests of PWMT, PWTL and spontaneous pain scores after daily i.t. administration of the NFAT5 inhibitor KRN2 for 7 days after CCI modeling. CCI + KRN2 (5 µg kg−1) versus CCI + Vehicle, *p < 0.05, n = 8, CCI + KRN2 (20 µg kg−1) versus CCI + Vehicle, **p < 0.01, ***p < 0.001, n = 8, two‐way ANOVA with repeated measures followed by Tukey's multiple comparison test. E1‐E2) Behavioral tests of PWMT and PWTL after single i.t. administration of the NFAT5 inhibitor KRN2 on day 7 CCI‐treated rats. CCI + KRN2 (5 µg kg−1) versus CCI + Vehicle, *p < 0.05, ***p < 0.001, n = 8, CCI + KRN2 (20 µg kg−1) versus CCI + Vehicle, *p < 0.05, **p < 0.01, *** p < 0.001, n = 8, two‐way ANOVA with repeated measures followed by Tukey's multiple comparison test. E3) Behavioral tests of spontaneous pain scores after single i.t. administration of the NFAT5 inhibitor KRN2 on day 7 CCI‐treated rats. CCI + KRN2 (5 µg kg−1) versus CCI + Vehicle, *p < 0.05, n = 8, CCI + KRN2 (20 µg kg−1) versus CCI + Vehicle, ***p < 0.001, n = 8, one‐way ANOVA followed by Tukey's multiple comparison test.