Ligustilide Relieves Complete Freund's Adjuvant-induced Mechanical Hyperalgesia through Inhibiting the Activation of Spinal c-Jun N-terminal Kinase/c-Jun Pathway in Rats

BACKGROUND: Ligustilide, an active ingredient in a traditional Chinese medicine, has anti-inflammatory and analgesic effects. The underlying mechanisms of the anti-inflammatory pain effects of ligustilide are not completely understood. OBJECTIVE: The aim of this study to investigate whether ligustilide conducts its analgesic effects on the complete Freund's adjuvant (CFA)-induced inflammatory pain through regulating the c-Jun N-terminal kinase (JNK)/c-Jun pathway in the spinal cord. MATERIALS AND METHODS: Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) were tested to examine the analgesic effect of ligustilide on CFA-induced inflammatory pain in rats. The change of spinal JNK/c-Jun activation was detected by western blotting after CFA injection with or without consecutive intrathecal ligustilide administration. After SP600125 (JNK inhibitor) was intrathecally injected in CFA rats, PWTs and PWLs were tested to investigate the change of ligustilide's analgesic effect. RESULTS: Repeated intravenous injection of ligustilide could attenuate the pain hypersensitivity induced by CFA. CFA caused increased activation of spinal JNK/c-Jun, which could be inhibited by ligustilide administration. Intrathecal injection of JNK inhibitor inhibited the CFA-induced mechanical hyperalgesia. CONCLUSION: Ligustilide could inhibit the upregulation of spinal p-JNK/p-c-Jun caused by CFA, and the inhibition of JNK/c-Jun activation is closely related to its anti-mechanical hyperalgesia effect in inflammatory pain. SUMMARY: Ligustilide, an active ingredient in a popular traditional Chinese medicine, has effective anti-inflammatory and analgesic effects. Ligustilide inhibits the complete Freund's adjuvant-induced activation of spinal c-Jun N-terminal kinase-(JNK)/c-Jun pathway in rats. The inhibition of JNK/c-Jun activation is closely related to the anti-mechanical hyperalgesia effect of ligustilide. [Image: see text] Abbreviations used: CFA: Complete Freund's adjuvant, JNK: c-Jun N-terminal kinase, MAPK: Mitogen-activated protein kinase, PWT: Paw withdrawal threshold, PWL: Paw withdrawal latency.