【Abstract】 Objective To study the effect of ozone on pain in mice with CCI, and to clarify the role of Homer1b/c in the spinal cord of CCI mice. Methods According to the random number table method,72 male Kunming mice were divided into 9 groups (n=8): group sham operation(group S1), group CCI to day 7(C1), group CCI to day 13(C2), group oxygen control(S2), group single injection(O1), group O1 to day 13(O2), group multiple injections(O3), Antisense oligonucleotide intervention group(AS), group saline control group(NS). All mice selected the left sciatic nerve to establish the CCI model. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were observed on the 7th day after model establishment. Western blot was used to detect the levels of Homer1b/c, metabotropic glutamate receptor 5 (mGluR5) and pERK protein in spinal cord. The distribution and expression of Homer1b/c and mGluR5 in spinal cord were detected by immunofluorescence. Results The MWT and TWL values of the C1 group were lower than those of the S1 group (P0.05). Compared with the C1 group, the MWT value of the O1 group was higher (P0.05), but the TWL value had no statistical difference (P0.05). Compared with the S2 group, the O2 group only increased the MWT value at 2h and 4h of ozone injection (P0.05). Compared with the C2 group, the MWT value of the O3 group increased each day (P0.05). Compared with NS group, AS group had higher MWT value 8th day after operation (P0.05). Compared with the S1 group, the protein expressions of Homer1b/c and pERK in the C2 group were increased (P0.05), the protein expression in the O3 group was decreased compared with the C2 group (P0.05), and the protein expression in the AS group was also decreased compared with the NS group (P0.05). Immunofluorescence showed that the expression of Homer1b/c in the dorsal horn of the spinal cord in the C2 group was increased compared with the S1 group, the expression of Homer1b/c in the O3 group was decreased compared with the C2 group, and the expression of Homer1b/c in the AS group was decreased compared with the NS group. Conclusions Ozone can inhibit mechanical pain in CCI mice, and the mechanism may be to inhibit the production of Homer1b/c and reduce the interaction with mGluR5.