Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Clinical Research Center for Pain Medicine in Hunan Province, Changsha, Hunan, China.
J Headache Pain. 2023 Oct 24;24(1):143. doi: 10.1186/s10194-023-01681-3.
BMP7 has been shown to have neuroprotective effects and to alleviate demyelination. However, its role in trigeminal neuralgia (TN) has not been well investigated. The current study aims to determine whether BMP7 plays a role in demyelination, its effects on pain behaviors and mechanism of action in rats with TN.
We used an infraorbital-nerve chronic-constriction injury (ION-CCI) to establish a rat model of TN. Adeno-associated viruses (AAVs) were injected into the rats to upregulate or downregulate BMP7. The mechanical withdrawal thresholds (MWT) of the injured rats were detected using Von Frey filaments. The changes in expression levels of BMP7 and oligodendrocyte (OL) markers were examined by western blotting, quantitative real-time PCR, immunofluorescence, and transmission electron microscopy.
The ION-CCI induced mechanical allodynia, demyelination, and loss of OLs with a reduction of BMP7. Short-hairpin RNA (shRNA)-BMP7 that inhibited BMP7 expression also caused mechanical allodynia, demyelination, and loss of OLs, and its mechanism may be OL apoptosis. Overexpressing BMP7 in the trigeminal spinal subnucleus caudalis(VC) with AAV-BMP7 relieved all three phenotypes induced by the CCI, and its mechanism may be alleviating OLs apoptosis. Two signal pathways associated with apoptosis, STAT3 and p65, were significantly downregulated in the VC after CCI and rescued by BMP7 overexpression.
BMP7 can alleviate TN by reducing OLs apoptosis and subsequent demyelination. The mechanism behind this protection could be BMP7-mediated activation of the STAT3 and NF-κB/p65 signaling pathway and subsequent decrease in OL apoptosis. Importantly, our study presents clear evidence in support of BMP7 as a possible therapeutic target for the treatment of TN.
BMP7 已被证明具有神经保护作用，并能减轻脱髓鞘。然而，其在三叉神经痛（TN）中的作用尚未得到充分研究。本研究旨在确定 BMP7 是否在脱髓鞘中发挥作用，及其对 TN 大鼠疼痛行为和作用机制的影响。
我们使用眶下神经慢性缩窄损伤（ION-CCI）建立 TN 大鼠模型。将腺相关病毒（AAVs）注射到大鼠体内以上调或下调 BMP7。使用 Von Frey 纤维检测受伤大鼠的机械退缩阈值（MWT）。通过 Western blot、实时定量 PCR、免疫荧光和透射电镜检测 BMP7 和少突胶质细胞（OL）标志物的表达水平变化。
ION-CCI 诱导机械性痛觉过敏、脱髓鞘和 OL 丢失，BMP7 减少。抑制 BMP7 表达的短发夹 RNA（shRNA-BMP7）也引起机械性痛觉过敏、脱髓鞘和 OL 丢失，其机制可能是 OL 凋亡。AAV-BMP7 在三叉神经根尾侧亚核（VC）中过表达 BMP7 可缓解 CCI 诱导的所有三种表型，其机制可能是减轻 OL 凋亡。CCI 后 VC 中与凋亡相关的两条信号通路 STAT3 和 p65 明显下调，BMP7 过表达可挽救。
BMP7 可通过减少 OL 凋亡和随后的脱髓鞘来缓解 TN。这种保护作用的机制可能是 BMP7 介导的 STAT3 和 NF-κB/p65 信号通路的激活，随后减少 OL 凋亡。重要的是，我们的研究提供了明确的证据支持 BMP7 作为治疗 TN 的可能治疗靶点。
