Natural (+)-camphor alleviates migraine induced by reserpine with local cerebral vasospasm via inhibiting p38β MAPK/ATF2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathogenesis of migraine model by reserpine with local cerebral vasospasm matches the characteristics of migraine with cold-coagulation in traditional Chinese medicine (TCM). Natural (+)-camphor (NC) is one of the Chinese herbal medicines with heat property, which is known to be effective in expelling cold and alleviating pain in TCM.

AIM OF THE STUDY: The proteomic analysis of migraine model by reserpine with local cerebral vasospasm and effect of NC was investigated to delineate the possible underlying mechanism.

MATERIALS AND METHODS: Mice brain proteomic analysis was carried out by data-independent acquisition mass spectrometry. The biological information of differentially-expressed proteins was analyzed based on Kyoto Encyclopedia of Genes and Genomes analysis. Animal behavior, brain histopathology and NO generation assay were observed.

RESULTS: Compared with normal, migraine mice had lower pain threshold, severe brain lesion and reduced NO content in serum. NC could improve pathological change. A total of 479 differentially-expressed proteins were identified. 8significant differential proteins were focused based on analysis. The distinctive proteins are commonly related to MAPK signaling pathway, and p38β MAPK was validated, which was excessively expressed in migraine mice. NC could mitigate cold-coagulation migraine symptoms by regulating NO production via inhibiting p38β MAPK/ATF2 pathway.

CONCLUSION: NC showed analgesic effect, and p38β MAPK was most likely to be the targets against vasospastic cold-coagulation migraine.