Mechanism of SGCs-HMGB1 axis-mediated peripheral sensitization in migraine based on neuroimmune microenvironment of trigeminal ganglion and traditional Chinese medicine intervention

04/09/2026

AI Summary

TG SGCs HMGB1 amplification loop in trigeminal ganglion drives peripheral sensitization and pain chronification via neuroimmune microenvironment imbalance.
Neuronal and SGCs release of HMGB1 activates receptors and inflammasomes, amplifying local inflammation and neuronal excitability.
Active components of traditional Chinese medicine inhibit SGC activation, HMGB1 externalisation, or block receptors and downstream signalling, offering targeted interventions.

AI Summary

Previous studies have shown that SGCs activation, HMGB1 externalization, and its downstream inflammatory cascades collectively contribute to neuroimmune imbalance within the TG, and may constitute an important amplification loop driving peripheral sensitization in migraine.

In addition, existing studies have systematically indicated that active components of TCM may exert anti-inflammatory and analgesic effects by inhibiting SGCs activation, interfering with HMGB1 release, or blocking its receptors and downstream signaling pathways, further suggesting that the TG-SGCs-HMGB1 axis plays a critical role in the pathogenesis of migraine.

The novelty of this review lies in proposing an integrated framework in which the TG-SGCs-HMGB1 amplification loop serves as a pivotal hub of peripheral sensitization, and in summarizing relevant research progress from the perspectives of TCM pathogenesis and node-based intervention by TCM, with the aim of providing references for mechanistic studies of migraine and precise intervention by TCM.

Basic summary

Zhongguo Zhong Yao Za Zhi. 2026 Aug;51(16):4545-4553. doi: 10.19540/j.cnki.cjcmm.20260430.363.

ABSTRACT

Migraine is a common neurovascular disorder, and its chronification and recurrent attacks are closely associated with peripheral sensitization. Trigeminal ganglion(TG) is an important initial site of peripheral sensitization in migraine, in which neurons and satellite glial cells(SGCs) are major contributors. The neuroimmune microenvironment composed of the two plays a key role in pain signal amplification. Upon external stimulation, neurons and SGCs can release alarmin high mobility group protein B1(HMGB1), which binds to specific receptors to activate inflammasomes, thereby further amplifying local inflammatory responses and neuronal excitability. Previous studies have shown that SGCs activation, HMGB1 externalization, and its downstream inflammatory cascades collectively contribute to neuroimmune imbalance within the TG, and may constitute an important amplification loop driving peripheral sensitization in migraine. In TCM, the pathogenesis of migraine is closely related to wind, heat, phlegm, and blood stasis. These pathological changes are, to some extent, consistent with the dysregulation of the TG neuroimmune microenvironment, the sustained release of inflammatory mediators, and the chronification of pain. In addition, existing studies have systematically indicated that active components of TCM may exert anti-inflammatory and analgesic effects by inhibiting SGCs activation, interfering with HMGB1 release, or blocking its receptors and downstream signaling pathways, further suggesting that the TG-SGCs-HMGB1 axis plays a critical role in the pathogenesis of migraine. The novelty of this review lies in proposing an integrated framework in which the TG-SGCs-HMGB1 amplification loop serves as a pivotal hub of peripheral sensitization, and in summarizing relevant research progress from the perspectives of TCM pathogenesis and node-based intervention by TCM, with the aim of providing references for mechanistic studies of migraine and precise intervention by TCM.

PMID:42693009 | DOI:10.19540/j.cnki.cjcmm.20260430.363

Document this CPD