Highlights • MC-OEC and OEC transplantation could reduce the expression levels of P2 × 7 receptor. • MC-OEC and OEC transplantation could relieve neuropathic pain. • The therapeutic efficacy was better in the MC-OEC group than in the OEC group. Abstract Objectives The aim of this study was to determine the role of microencapsulated olfactory ensheathing cell (MC-OEC) transplantation in rats with sciatic nerve injury-induced pain, and its relationship with P2 × 7 receptor expression in the L4-5 spinal cord segment. Methods Olfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells using differential attachment methods. Forty-eight healthy SD rats were randomly assigned to four groups: the sham, chronic constriction injury (CCI), olfactory ensheathing cell (OEC), and MC-OEC groups. Mechanical paw withdrawal thresholds were measured on days 7 and 14 after surgery. The expression of P2 × 7 receptor genes in the L4-5 spinal segment was detected by in situ hybridization and western blotting. Results On post-surgical days 7 and 14, the mechanical paw withdrawal thresholds of rats in the MC-OEC, OEC and CCI were lower than that in the sham group. The mechanical paw withdrawal thresholds of rats in the MC-OEC and OEC were higher than that in the CCI group, compared with the OEC group. The mechanical paw withdrawal thresholds of rats in the MC-OEC were increased. The expression levels of P2 × 7 receptors in the L4-5 spinal cord segment in the CCI, OEC and MC-OEC were higher than that in the sham group, the expression levels of P2 × 7 receptors in the MC-OEC and OEC group were lower than that in the CCI group, compared with the OEC group, the expression levels of P2 × 7 receptors in the MC-OEC were decreased. All differences between groups were statistically significant (P value <0.05). Conclusions OEC and MC-OEC transplantation can relieve pain and reduce the expression level of P2 × 7 receptors in the L4-5 spinal cord segment. The therapeutic efficacy was better in the MC-OEC group than in the OEC group. [ABSTRACT FROM AUTHOR]