BMP7 alleviates trigeminal neuralgia by suppressing oxidative stress and activation of satellite glial cells via the NRF2/HO-1 pathway.

Abstract

BACKGROUND: The trigeminal ganglion (TG) is a central hub for craniofacial injurious messaging, and its abnormal function is closely related to the pathogenesis of trigeminal neuralgia (TN). Bone morphogenetic protein 7 (BMP7), a pleiotropic cytokine with both neuroprotective and anti-inflammatory effects, has been shown to have therapeutic potential for neuropathic pain (NP) and neurodegenerative diseases. However, it remains to be elucidated whether BMP7 is involved in the pathological process of TN through the regulation of TG. OBJECTIVE: This study aimed to investigate whether BMP7 alleviates TN by modulating oxidative stress and activation in satellite glial cells (SGCs) of the TG. METHODS: A rat model of TN was established by chronic constriction injury of the distal infraorbital nerve (CCI-dION). Primary rat SGCs were activated with IL-1β to create an in vitro model. The role of BMP7 in regulating oxidative stress was assessed through in vivo knockdown and in vitro overexpression experiments. The NRF2 inhibitor ML385 was employed to validate the essential role of the NRF2/HO-1 pathway in BMP7-mediated SGC functional modulation. RESULTS: Following successful CCI-dION model establishment, TN rats showed significantly reduced mechanical pain thresholds, aggravated cold allodynia, and increased spontaneous pain behaviors, accompanied by decreased BMP7 expression, enhanced SGC activation, and elevated ROS levels in TG. These pathological phenotypes were consistently reproduced in BMP7-knockdown rats. In IL-1β-stimulated SGCs, BMP7 silencing mimicked pathological changes, while BMP7 overexpression reversed IL-1β effects - a rescue blocked by ML385. Critically, in vivo BMP7 overexpression attenuated CCI-dION-induced pain, oxidative stress, and SGC activation. CONCLUSION: This study demonstrates that BMP7 alleviates TN by suppressing oxidative stress and activation of SGCs through activation of the NRF2/HO-1 pathway, highlighting its therapeutic potential for TN treatment.