Marchand James E, Wurm Heinrich W, Kato Toshimasa, Kream Richard M
Anesthesia Research, Department of Anesthesiology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111, USA.
Pain. 1994 Aug;58(2):219-231. doi: 10.1016/0304-3959(94)90202-X.
The experiments described in the present study approached nerve injury from both a biochemical and anatomical perspective by monitoring changes in expression of preprotachykinin (PPT) mRNA encoding the prototypic tachykinin substance P and related peptide species in neurons of the rat dorsal root ganglia (DRG) following unilateral chronic constriction injury of the sciatic nerve. In situ hybridization histochemistry (ISHH) analyses in conjunction with computer-assisted image processing were employed to quantify levels of PPT mRNA distributed in DRG neurons. Injury-induced changes in PPT mRNA expression by affected DRG neurons included: (1) at early postoperative times, generally increased levels of PPT mRNA associated with small and intermediate-size B cells exhibiting normal morphology, (2) at late postoperative times, markedly decreased levels of PPT mRNA associated with degenerating B cells, and (3) induction of PPT gene expression by large A cells which is highly correlated with degenerative morphological changes. The significant aspects of these changes are discussed with special emphasis on the contribution of altered transmitter expression by DRG neurons to the pathophysiology of causalgia. In particular, the induction of PPT gene expression by many of the large neurons undergoing degenerative changes may represent an important biochemical parameter which is associated with the development and persistence of experimental allodynia.
本研究中所描述的实验，通过监测坐骨神经单侧慢性压迫损伤后大鼠背根神经节（DRG）神经元中编码典型速激肽P物质和相关肽类的前速激肽原（PPT）mRNA表达的变化，从生化和解剖学两个角度研究神经损伤。采用原位杂交组织化学（ISHH）分析结合计算机辅助图像处理来量化DRG神经元中分布的PPT mRNA水平。受影响的DRG神经元中损伤诱导的PPT mRNA表达变化包括：（1）术后早期，与形态正常的小和中等大小B细胞相关的PPT mRNA水平普遍升高；（2）术后晚期，与退化B细胞相关的PPT mRNA水平显著降低；（3）大A细胞诱导PPT基因表达，这与退化形态学变化高度相关。讨论了这些变化的重要方面，特别强调了DRG神经元递质表达改变对灼性神经痛病理生理学的贡献。特别是，许多发生退化性变化的大神经元诱导PPT基因表达可能代表了一个重要的生化参数，它与实验性异常性疼痛的发生和持续有关。
