Bupleurum falcatum L. alleviates nociceptive and neuropathic pain: Potential mechanisms of action

Ethnopharmacological relevance: In Iranian folkloric medicine, Bupleurum falcatum L. (Chinese Thoroughwax) has been used as a selective analgesic remedy for several centuries. Objective: The current research was conducted to explore the anti-nociceptive and anti-allodynic action of Bupleurum falcatum L. roots essential oil (BFEO) in Swiss mice. Materials and methods: Formalin-induced paw licking (FIPL) model was applied for exploring of BFEO antinociceptive effects (neurogenic or inflammatory pain). The involvements of L-arginine?NO?cGMP-KATP channel pathway and several receptors such as opioid, peroxisome proliferator-activated (PPA), cannabinoid, transient receptor potential vanilloid, and adrenergic receptors were assesses to detect the anti-nociceptive activity of BFEO. Cervical spinal cord contusion (CSC) paradigm was employed for induction of neuropathic pain. Results: BFEO (100 mg/kg), in the FIPL model, produced significant antinociception compared to the control mice (p < 0.01). Furthermore, L-arginine, methylene blue, glibenclamide, naloxonazine, GW9662, and SR141716A pre-treatments restored the BFEO anti-nociceptive effects (p < 0.05) in the FIPL (second phase) test (p < 0.05). Intraperitoneal administration of saikosaponin A (one of the main constituents of BFEO) partially alleviated (p < 0.05) pain in FIPL test. Likewise, in CSC mice, the von Frey assay exhibited that BFEO could alter mechanical allodynia. Conclusion: Finally, it seems that, in male mice, BFEO has both anti-allodynic and anti-nociceptive effects. The present data also suggest activating the L-arginine?NO?cGMP-KATP channel pathway as well as interaction of opioid, PPA, and cannabinoid receptors in the BFEO anti-nociceptive activities. These results also propose that BFEO could effectively attenuate allodynia in CSC mice.