Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China.
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China.
Neurosci Lett. 2019 Sep 14;709:134375. doi: 10.1016/j.neulet.2019.134375. Epub 2019 Jul 23.
Neuropathic pain induced by peripheral nerve injury is a complex and chronic state that is accompanied by poor quality of life. However, whether PIM1 (proviral integration site 1) contributes to the development of nociceptive hypersensitivity induced by nerve injury remains unknown. The present study was designed to investigate the effects of PIM1 on spinal nerve ligation (SNL) induced pain hypersensitivity. Here, we found that PIM1 positive neurons in the dorsal root ganglion (DRG) were colocalized with nociceptive neuronal markers CGRP, IB4 and substance P and were upregulated after SNL surgery. Knockdown PIM1 in the DRG by AAV5-shPIM1 alleviated SNL-induced pain hypersensitivity. In neuroblastoma cells (neuro-2a), PIM1 regulated the expression of CXCR4 phosphorylated at ser339 (pCXCR4) as well as the CXCL12/CXCR4 pathway. In the DRG tissues, we found that PIM1 was co-expressed with CXCR4, and knockdown of PIM1 attenuated pCXCR4 (ser339) protein expression but had little effect on total CXCR4 protein expression after SNL surgery. These findings suggest that PIM1 contributes to nerve injury-induced nociceptive hypersensitivity. Based on these findings and the characteristics of PIM1, we speculate that PIM1 might be a viable therapeutic target for the treatment of neuropathic pain in the near future.
外周神经损伤引起的神经性疼痛是一种复杂且慢性的状态，伴有生活质量下降。然而，PIM1（前病毒整合位点 1）是否有助于神经损伤引起的伤害性感受过敏的发展尚不清楚。本研究旨在探讨 PIM1 对脊神经结扎（SNL）诱导的痛觉过敏的影响。在这里，我们发现背根神经节（DRG）中 PIM1 阳性神经元与伤害性神经元标志物 CGRP、IB4 和 P 物质共定位，并且在 SNL 手术后上调。通过 AAV5-shPIM1 敲低 DRG 中的 PIM1 减轻了 SNL 诱导的痛觉过敏。在神经母细胞瘤细胞（Neuro-2a）中，PIM1 调节 CXCR4 磷酸化丝氨酸 339 位（pCXCR4）以及 CXCL12/CXCR4 途径的表达。在 DRG 组织中，我们发现 PIM1 与 CXCR4 共表达，敲低 PIM1 可减轻 pCXCR4（丝氨酸 339 位）蛋白表达，但对 SNL 手术后总 CXCR4 蛋白表达影响不大。这些发现表明 PIM1 有助于神经损伤引起的伤害性感受过敏。基于这些发现和 PIM1 的特征，我们推测 PIM1 可能是治疗神经性疼痛的一个有前途的治疗靶点。
