Objective:To evaluate the relationship between spinal cord cytoplasmic activation/proliferation-associated protein-1 (Caprin-1)-mediated expression of calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and pain perception in mice.Methods:Nestin CreERT2 mice and Caprin-1 flox/flox mice were hybridized to obtain Nestin CreERT2; Caprin-1 flox/flox homozygous mice. The mice were divided into 2 groups ( n=5 each) using a random number table method: Nestin CreERT2; Caprin-1 flox/floxsolventcontrol group (SC group) and Caprin-1 gene knockout group (KO group). Tamoxifen 100 mg/kg was intraperitoneally injected for 5 consecutive days to generate inducible knockout of the Caprin-1 gene in KO group. The mechanical paw withdrawal threshold was measured at day 1 before and day 5 after the end of administration. Then the mice were sacrificed, and L 4-6 segments of the spinal cord were removed for determination of the expression of Caprin-1 and CaMKⅡα protein and mRNA (by Western blot or real-time quantitative polymerase chain reaction) and co-expression of Caprin-1 with CaMKⅡα (by immunofluorescent double staining). Results:Compared with SC group, the mechanical paw withdrawal threshold was significantly increased at 5 days after the end of tamoxifen administration, the expression of Caprin-1 and CaMKⅡα protein and mRNA was down-regulated ( P<0.05), and the co-localization expression of Caprin-1 and CaMKⅡα in the spinal dorsal horn was down-regulated in KO group. Conclusions:Caprin-1 is involved in the development of pain perception by promoting CaMKⅡα expression.