Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Department of Microanatomy and Cellular Biology, Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
Nutrients. 2024 Oct 21;16(20):3563. doi: 10.3390/nu16203563.
Neuroinflammation and mitochondrial dysfunction have been implicated in the progression of neuropathic pain (NP) but can be mitigated by supplementation with gingerol-enriched ginger (GEG). However, the exact benefits of GEG for each sex in treating neuroinflammation and mitochondrial homeostasis in different brain regions and the colon remain to be determined.
Evaluate the effects of GEG on emotional/affective pain and spontaneous pain behaviors, neuroinflammation, as well as mitochondria homeostasis in the amygdala, frontal cortex, hippocampus, and colon of male and female rats in the spinal nerve ligation (SNL) NP model.
One hundred rats (fifty males and fifty females) were randomly assigned to five groups: sham + vehicle, SNL + vehicle, and SNL with three different GEG doses (200, 400, and 600 mg/kg BW) for 5 weeks. A rat grimace scale and vocalizations were used to assess spontaneous and emotional/affective pain behaviors, respectively. mRNA gene and protein expression levels for tight junction protein, neuroinflammation, mitochondria homeostasis, and oxidative stress were measured in the amygdala, frontal cortex, hippocampus, and colon using qRT-PCR and Western blot (colon).
GEG supplementation mitigated spontaneous pain in both male and female rats with NP while decreasing emotional/affective responses only in male NP rats. GEG supplementation increased intestinal integrity (claudin 3) and suppressed neuroinflammation [glial activation (GFAP, CD11b, IBA1) and inflammation (TNFα, NFκB, IL1β)] in the selected brain regions and colon of male and female NP rats. GEG supplementation improved mitochondrial homeostasis [increased biogenesis (TFAM, PGC1α), increased fission (FIS, DRP1), decreased fusion (MFN2, MFN1) and mitophagy (PINK1), and increased Complex III] in the selected brain regions and colon in both sexes. Some GEG dose-response effects in gene expression were observed in NP rats of both sexes.
GEG supplementation decreased emotional/affective pain behaviors of males and females via improving gut integrity, suppressing neuroinflammation, and improving mitochondrial homeostasis in the amygdala, frontal cortex, hippocampus, and colon in both male and female SNL rats in an NP model, implicating the gut-brain axis in NP. Sex differences observed in the vocalizations assay may suggest different mechanisms of evoked NP responses in females.
神经炎症和线粒体功能障碍与神经性疼痛（NP）的进展有关，但可以通过补充姜烯酚富集姜（GEG）来减轻。然而，GEG 对治疗不同脑区和结肠中神经炎症和线粒体动态平衡的每个性别的确切益处仍有待确定。
评估 GEG 对雄性和雌性 Spinal Nerve Ligation（SNL）NP 模型大鼠杏仁核、前额皮质、海马体和结肠中情感/情感痛和自发性疼痛行为、神经炎症以及线粒体动态平衡的影响。
将 100 只大鼠（50 只雄性和 50 只雌性）随机分为 5 组：假手术+载体、SNL+载体和 SNL 加三种不同剂量的 GEG（200、400 和 600mg/kgBW），共 5 周。使用大鼠面部表情评分和发声来分别评估自发性和情感/情感疼痛行为。使用 qRT-PCR 和 Western blot（结肠）测量杏仁核、前额皮质、海马体和结肠中紧密连接蛋白、神经炎症、线粒体动态平衡和氧化应激的 mRNA 基因和蛋白表达水平。
GEG 补充剂减轻了雄性和雌性 NP 大鼠的自发性疼痛，同时仅降低了雄性 NP 大鼠的情感/情感反应。GEG 补充剂增加了肠道完整性（闭合蛋白 3）并抑制了选定脑区和结肠中的神经炎症[神经胶质激活（GFAP、CD11b、IBA1）和炎症（TNFα、NFκB、IL1β）]在雄性和雌性 NP 大鼠中。GEG 补充剂改善了选定脑区和结肠中的线粒体动态平衡[增加生物发生（TFAM、PGC1α），增加裂变（FIS、DRP1），减少融合（MFN2、MFN1）和噬线体（PINK1），增加复合物 III]在两种性别中。在两种性别 NP 大鼠中观察到一些 GEG 剂量反应基因表达。
GEG 补充剂通过改善肠道完整性、抑制神经炎症和改善杏仁核、前额皮质、海马体和结肠中的线粒体动态平衡，降低了雄性和雌性 NP 大鼠的情感/情感疼痛行为，这表明肠道-大脑轴在 NP 中起作用。在发声测定中观察到的性别差异可能表明女性诱发 NP 反应的机制不同。
