Die Pharmazie · 2016
Ligustrazine attenuates neuropathic pain by inhibition of JAK/STAT3 pathway in a rat model of chronic constriction injury.
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Wang Shenggang, Li Aifeng, Guo Shengdong
Аннотация
AIM: Neuropathic pain is a common clinical complication of nerve injury, and the effective treatment of neuropathic pain is still challenging. Ligustrazine is mainly used for the treatment of cardiovascular disease and its role in neuropathic pain is less investigated. The purpose of our study was to explore the effects of ligustrazine on neuropathic pain, as well as the underlying molecular mechanism.
METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in Sprague-Dawley (SD) rats. After CCI, rats received ligustrazine, IL-6, or both. Mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were assessed on days 1, 3, 7, and 14 after surgery. Expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-β, IL-2, and phosphorylation of Signal Transducer and Activator of Transcription (STAT) 3 were analyzed.
RESULTS: Our results showed that both MWT and PWTL were significantly decreased by CCI on days 1, 3, 7 and 14 compared to sham group, however, ligustrazine reversed this effects. Additionally, the elevated levels of TNF-α, IL-1β, and IL-2 in CCI spinal cord were inhibited by ligustrazine. Quantitative real-time (qRT-PCR) and Western blotting analysis showed that the test substance reduced the elevated expression of pSTAT3 in the spinal cord induced by CCI, and while IL-6 administration reversed the levels as well as the behavior responses.
CONCLUSION: Our results suggest that ligustrazine could effectively attenuate neuropathic pain by inhibition of Janus Kinase (JAK)/STAT3 pathway in CCI rats.
METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in Sprague-Dawley (SD) rats. After CCI, rats received ligustrazine, IL-6, or both. Mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were assessed on days 1, 3, 7, and 14 after surgery. Expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-β, IL-2, and phosphorylation of Signal Transducer and Activator of Transcription (STAT) 3 were analyzed.
RESULTS: Our results showed that both MWT and PWTL were significantly decreased by CCI on days 1, 3, 7 and 14 compared to sham group, however, ligustrazine reversed this effects. Additionally, the elevated levels of TNF-α, IL-1β, and IL-2 in CCI spinal cord were inhibited by ligustrazine. Quantitative real-time (qRT-PCR) and Western blotting analysis showed that the test substance reduced the elevated expression of pSTAT3 in the spinal cord induced by CCI, and while IL-6 administration reversed the levels as well as the behavior responses.
CONCLUSION: Our results suggest that ligustrazine could effectively attenuate neuropathic pain by inhibition of Janus Kinase (JAK)/STAT3 pathway in CCI rats.