Coronel M F, Musolino P L, Brumovsky P R, Hökfelt T, Villar M J
School of Biomedical Sciences, Austral University, Buenos Aires, Argentina.
Neuropeptides. 2009 Apr;43(2):125-32. doi: 10.1016/j.npep.2008.12.003. Epub 2009 Jan 24.
Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers neuropathic pain-related behaviors and induces changes in neuropeptide expression in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and prevent mechanical and thermal allodynia. In this study, we have evaluated the effect of MSC administration on the expression of the neuropeptides galanin and NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. Animals were subjected to a sciatic nerve SLNC either alone or followed by the administration of MSCs, phosphate-buffered saline (PBS) or bone marrow non-adherent mononuclear cells (BNMCs), directly into the ipsilateral L4 DRG. Seven days after injury, the ipsilateral and contralateral L4-5 DRGs were dissected out and processed for standard immunohistochemistry, using specific antibodies. As previously reported, SLNC induced an ipsilateral increase in the number of galanin and NPY immunoreactive neurons and a decrease in Y(1)R-positive DRG neurons. The intraganglionic injection of PBS or BNMCs did not modify this pattern of expression. In contrast, MSC administration partially prevented the injury-induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R-immunoreactive neurons together with high levels of NPY expression in animals injected with MSCs could explain, at least in part, the analgesic effects exerted by these cells. Our results support MSC participation in the modulation of neuropathic pain and give insight into one of the possible mechanisms involved.
大鼠坐骨神经单结扎(SLNC)可引发与神经性疼痛相关的行为,并导致初级传入神经元中神经肽表达的变化。将骨髓基质细胞(MSC)注射到接受坐骨神经SLNC的动物的腰4(L4)背根神经节(DRG)中,这些细胞会选择性地迁移到同侧的其他腰DRG(L3、L5和L6),并预防机械性和热性痛觉过敏。在本研究中,我们评估了给予MSC对DRG神经元中神经肽甘丙肽和神经肽Y(NPY)以及NPY Y(1)受体(Y(1)R)表达的影响。动物单独接受坐骨神经SLNC,或在坐骨神经SLNC后直接向同侧L4 DRG注射MSC、磷酸盐缓冲盐水(PBS)或骨髓非贴壁单核细胞(BNMC)。损伤7天后,取出同侧和对侧的L4-5 DRG,使用特异性抗体进行标准免疫组织化学处理。如先前报道,SLNC导致同侧甘丙肽和NPY免疫反应性神经元数量增加,而Y(1)R阳性DRG神经元数量减少。向神经节内注射PBS或BNMC并未改变这种表达模式。相比之下,给予MSC部分预防了损伤诱导的甘丙肽、NPY和Y(1)R表达变化。在注射MSC的动物中,大量Y(1)R免疫反应性神经元以及高水平的NPY表达至少可以部分解释这些细胞所发挥的镇痛作用。我们的结果支持MSC参与神经性疼痛的调节,并深入了解其中一种可能的机制。