Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Research Institute of Galilee Medical Center, Nahariya, Israel.
Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Research Institute of Galilee Medical Center, Nahariya, Israel.
Neuropharmacology. 2024 Feb 1;243:109788. doi: 10.1016/j.neuropharm.2023.109788. Epub 2023 Nov 18.
The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar hypersensitivity induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects.
特发性疼痛病症（如激惹性外阴痛（PV））的病因是多因素的。文拉法辛（一种 5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRIs））在调节外阴疼痛方面的疗效，使人们产生了这样一种假设，即 PV 可能涉及中枢机制。在这里，我们研究外阴疼痛是否与情绪、应激和疼痛系统的基因表达变化有关，包括杏仁核（Amg）、内侧前额叶皮层（mPFC）和导水管周围灰质（PAG）。此外，我们还研究了文拉法辛的镇痛和抗焦虑作用。我们发现，在 PV 的动物模型中，慢性外阴疼痛的发展与 Amg、mPFC 和 PAG 中与神经元活性和神经炎症相关的基因表达过度有关。此外，还观察到 Amg 和 mPFC 中 GABA 和 5-羟色胺合成和再摄取的表达变化。毫不奇怪，慢性外阴疼痛的大鼠表现出类似焦虑的行为和情绪障碍。然而，用文拉法辛（37.5mg/kg）治疗一个月可显著改善外阴过敏，降低焦虑水平。更重要的是，长期使用文拉法辛治疗可调节外阴疼痛大鼠 Amg、mPFC 和 PAG 中 5-羟色胺受体和合成、GABA 合成、神经可塑性和神经炎症的基因表达适应性。我们的研究结果表明，炎症引起的外阴过敏可能与参与情绪、应激和疼痛调节的大脑区域的基因表达变化有关。这些变化可能在中枢敏化和焦虑中发挥作用。令人惊讶的是，通过增强外阴疼痛大鼠的 5-羟色胺和去甲肾上腺素的活性，文拉法辛治疗可产生镇痛和抗焦虑作用。
