Nerve ingrowth into diseased intervertebral disc in chronic back pain
Nerve ingrowth into diseased intervertebral disc in chronic back pain
复制标题
DOI：
10.1016/s0140-6736(97)02135-1
复制
发表时间：
1997-07-19
期刊：
影响因子：
168.9
通讯作者：
Jayson, MIV
中科院分区：
文献类型：
--
作者：
Freemont, AJ;Peacock, TE;Jayson, MIV
背景：在健康的背部，只有椎间盘纤维环的外1/3被神经支配。神经深入到病变的椎间盘中已有报道，但这一特征有多常见以及是否与慢性疼痛有关尚不清楚。方法收集38例慢性下腰痛患者在脊柱融合术中的46个椎间盘标本，观察神经生长在慢性腰痛发病机制中的作用。30个样本来自临床上经椎间盘造影术确定的疼痛水平，16个样本来自邻近椎体水平，没有疼痛。我们在有记录的死亡后8小时内，从组织结构正常的既往健康个体获得了34个对照样本。我们使用标准的免疫组织化学技术来检测一般神经标志物、伤害性神经递质(P物质)和轴突形成过程中表达的蛋白质(生长相关蛋白43[GAP43])。结果发现，在80个椎间盘样本中，有48个(60%)在纤维环外三分之一处发现了神经纤维。在34例对照标本中，神经被限制在纤维环的外或中1/3处。在慢性下腰痛患者中，有21例(46%)神经伸入纤维环内1/3，10例(22%)伸入髓核。神经通常伴随血管，但在14例背痛患者的样本中，在椎间盘基质中看到了孤立的神经纤维。两种类型的神经纤维都表达P物质，但只有非血管相关的神经纤维表达GAP43，在非疼痛水平的16例活检标本中有4例(25%)和疼痛水平的17例(57%)标本中可见深神经向纤维环内1/3、髓核或两者均有生长。在16个来自疼痛和非疼痛水平的配对样本中，5个疼痛水平样本和1个非疼痛水平样本显示神经深深扎根。解释我们发现的孤立神经纤维在病变的椎间盘深处表达P物质及其与疼痛的关系，表明神经生长进入椎间盘在慢性下腰痛的发病机制中起着重要作用。
Background 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.Methods 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]).Findings 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.Interpretation 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.