Key factors of microangiogenesis within herniated nucleus pulposus and effect on pain and functions

English Keywords:Lumbar disc herniation  Microvascular  Macrophage  Intervertebral disc degeneration  Nucleus pulposus  Intervertebral disc vascularisation

English Abstract:

  【Abstract】 Objectives: To investigate the key factors of microangiogenesis in nucleus pulposus and the impact on pain and function in patients with lumbar disc herniation(LDH). Methods: The clinical data of 181 patients diagnosed with LDH who underwent surgical treatment from August 2023 to August 2024 were retrospectively analyzed. The nucleus pulposus tissues were collected intraoperatively. The general data were collected, including gender, age, and herniated segments. Back pain visual analogue scale(VAS) scores, lower limb pain VAS scores, and Oswestry disability index(ODI) were recorded on admission to evaluate clinical symptoms. Meanwhile, the modifying Pfirrmann′s grading for intervertebral disc degeneration, Modic changes, annular integrity, herniation site and type, intervertebral disc height(IDH), herniated nucleus pulposus cross-sectional area, herniation rate, relative signal intensity(SI) of the herniated nucleus pulposus, and its signal intensity ratio(SIR) at the surgical segment were measured on X-ray films and MRIs. Expressions of CD34, CD68 and CD163 were observed by hematoxylin-eosin(HE) and immunohistochemical(IHC) staining. According to the IHC test result of CD34, an important marker of pathological microangiogenesis in the nucleus pulposus, the patients were divided into CD34(+) and CD34(-) groups. The two groups were compared in baseline data, clinical symptoms, disease duration, as well as imaging indicators for differences, and the correlation between microangiogenesis and macrophage infiltration was analyzed. Results: CD34(+) group consisted of 99 cases, and CD34(-) group consisted of 82 cases. There were no statistical differences in baseline data such as gender, age, and herniated segment between the two groups(P>0.05). The CD34(+) group showed significantly higher lumbar pain VAS scores, lower limb pain VAS scores, and ODI than the CD34(-) group(P<0.05). The CD34(+) group exhibited a longer disease duration. In terms of imaging, the CD34(+) group was more significant in the degree of degeneration, fibrous ring rupture rate, and type of herniation(P<0.05). However, the IDH, the relative SI of the herniated nucleus pulposus, and its SIR were significantly lower in the CD34(+) group than in the CD34(-) group(P<0.05), and the herniated nucleus pulposus area and herniation rate were significantly higher than those in the CD34(-) group(P<0.05). Differences between the two groups in terms of Modic changes and sites of herniation were not significant(P>0.05). Histological examination revealed that within the CD34(+) group, macrophage infiltration rate attained 93.94%, exhibiting a significant correlation with microvascular proliferation(P<0.05), with a strong correlation between the two(Lambda coefficient=0.89). Conclusions: Microvascular angiogenesis is commonly present in herniated nucleus pulposus tissue and it is significantly associated with the occurrence or exacerbation of pain. Long duration of illness, severe IDD, annulus fibrosus rupture, extrusive or sequestrated LDH, reduced IDH, increased herniated nucleus pulposus area and herniation rate, reduced SI and SIR are all key factors inducing microangiogenesis of the intervertebral disc.