Ligustilide attenuates hyperalgesia in an inflammatory pain rat model: involvement of spinal ERK/MAPK pathway and proinflammatory cytokines

The aim of this study is to examine the analgesic effect of ligustilide in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain, and to investigate whether the spinal ERK/MAPK pathway and the subsequent activation of proinflammatory cytokines were involved in ligustilide's anti-nociceptive effect. Adult male Sprague-Dawley rats were divided into three groups: Control+Vehicle, CFA+Vehicle, CFA+Ligustilide. The ligustilide was administrated intragastrically on 1 day before CFA injection, 0, 4, 8 h after CFA injection, and 1 day after injection. Paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) were measured. The change of the activation of spinal ERK1/2 and ERK5, and the level of IL-1 beta and TNF-alpha were detected by western blotting and ELISA on day 2 after CFA injection. The behavior results showed that consecutive intragastric administration of ligustilide alleviated the CFA-induced hyperalgesia. Ligustilide inhibited the CFA-induced increased activation of spinal ERK1/2 and ERK5, as well as reducing the increased production of IL-1 beta and TNF-alpha.