Freemont A J, Peacock T E, Goupille P, Hoyland J A, O'Brien J, Jayson M I
Department of Rheumatology, University of Manchester, UK.
Lancet. 1997 Jul 19;350(9072):178-81. doi: 10.1016/s0140-6736(97)02135-1.
In the healthy back only the outer third of the annulus fibrosus of the intervertebral disc is innervated. Nerve ingrowth deeper into diseased intervertebral disc has been reported, but how common this feature is and whether it is associated with chronic pain are unknown. We examined nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.
We collected 46 samples of intervertebral discs from 38 patients during spinal fusion for chronic back pain. 30 samples were from pain levels clinically established by discography and 16 samples were from adjacent vertebral levels with no pain. We obtained 34 control samples of intervertebral disc from previously healthy individuals with normal histology within 8 h of recorded death. We used standard immunohistochemical techniques to test for a general nerve marker, a nociceptive neurotransmitter (substance P), and a protein expressed during axonogenesis (growth-associated protein 43 [GAP43]).
We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%) of the 80 samples of intervertebral discs. Nerves were restricted to the outer or middle third of the annulus fibrosus in the 34 control samples. Among the patients with chronic low back pain, nerves extended into the inner third of the annulus fibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) samples, respectively. Nerves usually accompanied blood vessels, but in 14 of the samples from back-pain patients, isolated nerve fibres were seen in the discal matrix. Both types of nerve fibres expressed substance P, but only non-vessel-associated fibres expressed GAP43. Deep nerve ingrowth into the inner third of the annulus fibrosus, the nucleus pulposus, or both was seen in four (25%) of 16 biopsy samples from non-pain levels and in 17 (57%) samples from pain levels. Of the 16 paired samples from both pain and non-pain levels, five pain-level samples and one non-pain-level sample showed deep nerve ingrowth.
Our finding of isolated nerve fibres that express substance P deep within diseased intervertebral discs and their association with pain suggests an important role for nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.
在健康的脊柱中，仅椎间盘纤维环的外三分之一有神经支配。已有报道称神经向内生长深入到病变的椎间盘中，但这种特征的普遍程度以及它是否与慢性疼痛相关尚不清楚。我们研究了在慢性下腰痛发病机制中神经向椎间盘内的生长情况。
我们在为慢性背痛患者进行脊柱融合手术期间从38例患者身上收集了46个椎间盘样本。30个样本来自经椎间盘造影临床确定的疼痛节段，16个样本来自无疼痛的相邻椎体节段。我们从记录死亡后8小时内组织学正常的先前健康个体中获取了34个椎间盘对照样本。我们使用标准免疫组织化学技术检测一种通用神经标志物、一种伤害性神经递质（P物质）以及一种在轴突发生过程中表达的蛋白质（生长相关蛋白43 [GAP43]）。
在80个椎间盘样本中的48个（60%）中，我们在纤维环的外三分之一处发现了神经纤维。在34个对照样本中，神经局限于纤维环的外三分之一或中三分之一。在慢性下腰痛患者中，分别有21个（46%）和10个（22%）样本中的神经延伸到了纤维环的内三分之一和髓核。神经通常伴随血管，但在来自背痛患者的14个样本中，在椎间盘基质中可见孤立的神经纤维。两种类型的神经纤维都表达P物质，但只有与血管无关的纤维表达GAP43。在来自无疼痛节段的16个活检样本中的4个（25%）以及来自疼痛节段的17个（57%）样本中，可见神经深入生长到纤维环的内三分之一、髓核或两者。在来自疼痛和无疼痛节段的16对样本中，5个疼痛节段样本和1个无疼痛节段样本显示有神经深入生长。
我们发现在病变椎间盘中深处有表达P物质的孤立神经纤维，且它们与疼痛相关，这表明神经向椎间盘内生长在慢性下腰痛的发病机制中起重要作用。
