Weissner Wendy, Winterson Barbara J, Stuart-Tilley Alan, Devor Marshall, Bove Geoffrey M
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Comp Neurol. 2006 Jul 1;497(1):78-87. doi: 10.1002/cne.20981.
Recent evidence suggests that substance P (SP) is up-regulated in primary sensory neurons following axotomy and that this change occurs in larger neurons that do not usually produce SP. If this is so, then the up-regulation may allow normally neighboring, uninjured, and nonnociceptive dorsal root ganglion (DRG) neurons to become effective in activating pain pathways. By using immunohistochemistry, we performed a unilateral L5 spinal nerve transection on male Wistar rats and measured SP expression in ipsilateral L4 and L5 DRGs and contralateral L5 DRGs at 1-14 days postoperatively (dpo) and in control and sham-operated rats. In normal and sham-operated DRGs, SP was detectable almost exclusively in small neurons (< or =800 microm2). After surgery, the mean size of SP-positive neurons from the axotomized L5 ganglia was greater at 2, 4, 7, and 14 dpo. Among large neurons (>800 microm2) from the axotomized L5, the percentage of SP-positive neurons increased at 2, 4, 7, and 14 dpo. Among small neurons from the axotomized L5, the percentage of SP-positive neurons was increased at 1 and 3 dpo but was decreased at 7 and 14 dpo. Thus, SP expression is affected by axonal damage, and the time course of the expression is different between large and small DRG neurons. These data support a role for SP-producing, large DRG neurons in persistent sensory changes resulting from nerve injury.
最近的证据表明，在轴突切断后，初级感觉神经元中的P物质（SP）上调，并且这种变化发生在通常不产生SP的较大神经元中。如果是这样，那么这种上调可能会使通常相邻的、未受损的和非伤害性的背根神经节（DRG）神经元有效地激活疼痛通路。通过免疫组织化学方法，我们对雄性Wistar大鼠进行了单侧L5脊神经切断术，并在术后1至14天（dpo）测量了同侧L4和L5 DRG以及对侧L5 DRG中SP的表达，并与对照和假手术大鼠进行了比较。在正常和假手术的DRG中，几乎仅在小神经元（≤800平方微米）中可检测到SP。手术后，在2、4、7和14 dpo时，来自切断轴突的L5神经节的SP阳性神经元的平均大小更大。在切断轴突的L5的大神经元（> 800平方微米）中，SP阳性神经元的百分比在2、4、7和14 dpo时增加。在切断轴突的L5的小神经元中，SP阳性神经元的百分比在1和3 dpo时增加，但在7和14 dpo时降低。因此，SP表达受轴突损伤影响，并且大小不同的DRG神经元之间表达的时间进程也不同。这些数据支持产生SP的大DRG神经元在神经损伤导致的持续性感觉变化中起作用。
