Department of Oral Physiology School of Dentistry Kyungpook National University, Daegu, Republic of Korea.
Department of Dental Hygiene Kyung-Woon University, Gumi, Republic of Korea.
Pain Res Manag. 2024 Sep 27;2024:9179928. doi: 10.1155/2024/9179928. eCollection 2024.
Although previous studies suggest that Piezo2 regulates chronic pain in the orofacial area, few studies have reported the direct evidence of Piezo2's involvement in inflammatory and neuropathic pain in the orofacial region. In this study, we used male Sprague Dawley rats to investigate the role of the Piezo2 pathway in the development of inflammatory and neuropathic pain. The present study used interleukin (IL)-1-induced pronociception as an inflammatory pain model. Subcutaneous injection of IL-1 produced significant mechanical allodynia and thermal hyperalgesia. Subcutaneous injection of a Piezo2 inhibitor significantly blocked mechanical allodynia and thermal hyperalgesia induced by subcutaneously injected IL-1. Furthermore, the present study also used a neuropathic pain model caused by the misplacement of a dental implant, leading to notable mechanical allodynia as a consequence of inferior alveolar nerve injury. Western blot analysis revealed increased levels of Piezo2 in the trigeminal ganglion and the trigeminal subnucleus caudalis after inferior alveolar nerve injury. Furthermore, subcutaneous and intracisternal injections of a Piezo2 inhibitor blocked neuropathic mechanical allodynia. These results suggest that the Piezo2 pathway plays a critical role in the development of inflammatory and neuropathic pain in the orofacial area. Therefore, blocking the Piezo2 pathway could be the foundation for developing new therapeutic strategies to treat orofacial pain conditions.
虽然先前的研究表明 Piezo2 调节口腔面部区域的慢性疼痛，但很少有研究报道 Piezo2 直接参与口腔区域的炎症性和神经性疼痛。在这项研究中，我们使用雄性 Sprague Dawley 大鼠来研究 Piezo2 通路在炎症性和神经性疼痛发展中的作用。本研究使用白细胞介素 (IL)-1 诱导的伤害感受来作为炎症性疼痛模型。皮下注射 IL-1 会产生显著的机械性痛觉过敏和热痛觉过敏。皮下注射 Piezo2 抑制剂可显著阻断皮下注射 IL-1 引起的机械性痛觉过敏和热痛觉过敏。此外，本研究还使用了由牙种植体错位引起的神经性疼痛模型，导致下牙槽神经损伤后明显的机械性痛觉过敏。Western blot 分析显示，在下牙槽神经损伤后，三叉神经节和三叉神经尾核亚核中 Piezo2 的水平升高。此外，皮下和鞘内注射 Piezo2 抑制剂可阻断神经性机械性痛觉过敏。这些结果表明，Piezo2 通路在口腔面部区域的炎症性和神经性疼痛发展中起着关键作用。因此，阻断 Piezo2 通路可能为开发治疗口腔疼痛疾病的新治疗策略奠定基础。
