Ligustrazine inhibits high voltage-gated Ca²⁺ and TTX-resistant Na⁺ channels of primary sensory neuron and thermal nociception in the rat: A study on peripheral mechanism

Objective: Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods: Paw withdrawal Latency (PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results: Intraplantar injection of ligustrazine (0.5 mg in 25 μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC₅₀ of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC₅₀ of 2.49 mmol/L. Conclusion: The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.