Laboratory for Pain Research, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, Split 21000, Croatia.
Pain. 2011 May;152(5):1173-1181. doi: 10.1016/j.pain.2011.01.045. Epub 2011 Mar 3.
Neuropeptide Y (NPY) has an important but still insufficiently defined role in pain modulation. We therefore examined the ability of NPY to modulate experimentally induced neuropathic pain by injecting it directly into dorsal root ganglion (DRG) immediately following spinal nerve ligation (SNL) injury. We have found that this application exacerbates pain-related behavior induced by SNL in a modality-specific fashion. When saline was injected after SNL, the expected increase in hyperalgesia responses to needle stimulation was present on the 8th postoperative day. When we injected NPY, hyperalgesic responses were increased in a manner similar to the SNL/saline group. To characterize NPY action, specific Y1 and Y2 antagonists were also delivered directly to DRG, which revealed that behavioral actions of NPY were abolished by Y2 receptor antagonist. We tested whether NPY effects were the result of its role in immunity by immunohistochemical staining for glial fibrillary acidic protein, in order to identify activation of DRG satellite cells and dorsal horn astrocytes. Exacerbation of pain-related behavior following NPY injection was accompanied by astrocyte activation in ipsilateral dorsal horn and with satellite cells activation in the DRG proximal to injury. This activation was reduced following Y2 receptor antagonist application. These findings indicate an important link between pain-related behavior and neuroimmune activation by NPY through its Y2 receptor.
神经肽 Y（NPY）在疼痛调节中具有重要但尚未充分定义的作用。因此，我们通过在脊髓神经结扎（SNL）损伤后立即将其直接注射到背根神经节（DRG）中来检查 NPY 调节实验性神经病理性疼痛的能力。我们发现，这种应用以特定于模态的方式加剧了 SNL 引起的与疼痛相关的行为。当 SNL 后注射盐水时，在术后第 8 天出现了对针刺激的超敏反应的预期增加。当我们注射 NPY 时，超敏反应以类似于 SNL/盐水组的方式增加。为了表征 NPY 的作用，还将特异性 Y1 和 Y2 拮抗剂直接递送到 DRG，这表明 Y2 受体拮抗剂消除了 NPY 的行为作用。我们通过胶质纤维酸性蛋白的免疫组织化学染色来测试 NPY 效应是否是其在免疫中的作用的结果，以鉴定 DRG 卫星细胞和背角星形胶质细胞的激活。NPY 注射后疼痛相关行为的加剧伴随着同侧背角星形胶质细胞的激活以及损伤近端 DRG 中卫星细胞的激活。在应用 Y2 受体拮抗剂后，这种激活减少了。这些发现表明，NPY 通过其 Y2 受体与疼痛相关行为和神经免疫激活之间存在重要联系。
