Tetrandrine Alleviates Nociception in a Rat Model of Migraine via Suppressing S100B and p-ERK Activation in Satellite Glial Cells of the Trigeminal Ganglia.

Abstract

Sensitization and activation of the trigeminal ganglia have been implicated in the pathology of migraine. Satellite glial cells (SGCs), a specialized type of glial cells that ensheathe trigeminal neurons, may be critical for peripheral nociceptive sensitization. Tetrandrine (TET), an alkaloid extracted from a traditional Chinese herb, exerts an inhibitory effect on glial activation in vitro and has been used in various neurologic diseases. The current study investigated the effect of TET on nitroglycerin (NTG)-induced trigeminal sensitization and examined potential signaling pathways related to SGC activation in the model of migraine. We measured trigeminal nociceptive thresholds using electronic von Frey rigid tips before and after NTG injection in control rats and rats pretreated with TET, while expression and subcellular location of the inflammatory mediators S100B and activated phosphorylation extracellular signal-regulated kinase (p-ERK) were measured using real-time quantitative polymerase chain reaction, Western blotting, and double immunofluorescence staining. Pretreatment with TET caused a dose-dependent reversal of the trigeminal nociceptive hypersensitivity induced by NTG. In addition, TET pretreatment blocked the activation of S100B and p-ERK in trigeminal ganglion SGCs of NTG-treated rats. Reduced p-ERK activity can suppress the inflammation that leads to hyperexcitability of trigeminal ganglion neurons. Administration of TET may therefore be a safe and effective therapeutic treatment for the hyperalgesic symptoms of migraine.