Department of Pain, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, Hubei, China.
Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, Hubei, China.
Gene. 2019 Nov 30;719:144080. doi: 10.1016/j.gene.2019.144080. Epub 2019 Aug 24.
Trigeminal neuropathic pain is seen as a huge clinical challenge. Although numerous drugs have been developed to treat the condition, some patients have shown intolerance to the drugs and thus continue to suffer. In the present study, a rat model of trigeminal neuropathic pain was established using incorrectly positioned dental implants, which had various manifestations that were similar to human trigeminal neuropathic pain. Using this model, we investigated the differential regulation of JAK2 and PTEN. Firstly, we examined the expression of JAK2 and PTEN in the medullary dorsal horn. After inhibiting JAK2/PTEN, we evaluated nociception-related behavioral alterations. The rat models were established by replacing the left lower second molar with a mini dental implant. Immunoblot assay and immunofluorescence experiments indicated high expression of JAK2 and PTEN in medullary dorsal horn after the nerve injury, which attained plateau levels on post-operative day (POD) 5-10 and 10-20. Administration of adenovirus-shRNA-JAK2 on POD 1 reduced mechanical allodynia and downstream STAT activation. Meanwhile, the administration of adenovirus-shRNA-PTEN on POD 1 attenuated mechanical allodynia while upregulating AKT. In addition to postoperative JAK2 and PTEN activation, dexmedetomidine treatment (10 mg/kg) also modulated the downstream sensors of these signaling molecules. These data suggest that JAK2 and PTEN are pivotal to the development of trigeminal neuropathic pain, and that JAK2 and PTEN suppression alleviates the neuropathic pain.
三叉神经病理性疼痛被视为巨大的临床挑战。尽管已经开发出许多药物来治疗这种疾病，但一些患者对这些药物表现出不耐受，因此仍在遭受痛苦。在本研究中，使用位置不当的牙种植体建立了大鼠三叉神经病理性疼痛模型，该模型具有类似于人类三叉神经病理性疼痛的各种表现。使用该模型，我们研究了 JAK2 和 PTEN 的差异调节。首先，我们检查了 medullary dorsal horn 中 JAK2 和 PTEN 的表达。抑制 JAK2/PTEN 后，我们评估了与伤害感受相关的行为改变。通过用微型牙种植体替代左侧下颌第二磨牙来建立大鼠模型。免疫印迹分析和免疫荧光实验表明，神经损伤后 medullary dorsal horn 中 JAK2 和 PTEN 的表达升高，术后第 5-10 天和第 10-20 天达到平台水平。术后第 1 天给予腺病毒-shRNA-JAK2 可减轻机械性痛觉过敏和下游 STAT 激活。同时，术后第 1 天给予腺病毒-shRNA-PTEN 可减轻机械性痛觉过敏，同时上调 AKT。除了术后 JAK2 和 PTEN 的激活外，右美托咪定（10mg/kg）治疗还调节了这些信号分子的下游传感器。这些数据表明，JAK2 和 PTEN 对三叉神经病理性疼痛的发展至关重要，抑制 JAK2 和 PTEN 可减轻神经病理性疼痛。
