Neuropeptides in the human intervertebral disc

Ashton, I. K.; Roberts, Sally; Jaffray, David; Polak, Julia M.; Eisenstein, Stephen M.

doi:10.1002/jor.1100120206

Cited by 177 publications

(91 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found a total lack of all CGRP-, DBH-, and VIPimmunoreactive nerve fibres in the deeper parts of the intervertebral disc, as previously reported for both man 23 and the rat. [24][25][26] There have been reports, however, of sensory nerve fibres in the deeper parts of diseased discs in man 27,28 and also in the healing area of the medial collateral ligament of the rabbit knee.…”

Section: Discussionsupporting

confidence: 62%

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes

Suseki¹,

Takahashi²,

Takahashi³

et al. 1998

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

It has been thought that lumbar intervertebral discs were innervated segmentally. We have previously shown that the L5-L6 intervertebral disc in the rat is innervated bilaterally from the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunks, but the pathways between the disc and the paravertebral sympathetic trunks were unknown.We have now studied the spines of 17 rats to elucidate the exact pathways. We examined serial sections of the lumbar spine using immunohistochemistry for calcitonin gene-related peptide, a sensory nerve marker. We showed that these nerve fibres from the intervertebral disc ran through the sinuvertebral nerve into the rami communicantes, not into the corresponding segmental spinal nerve.In the rat, sensory information from the lumbar intervertebral discs is conducted through rami communicantes. If this innervation pattern applies to man, simple decompression of the corresponding nerve root will not relieve discogenic pain. Anterior interbody fusion, with the denervation of rami communicantes, may be effective for such low back pain. [Br] 1998;80-B:737-42. J Bone Joint Surg Received 4 August 1997; Accepted after revision 8 January 1998Lumbar intervertebral discs and facet joints are possible sources of low back pain, 1-3 but they have been considered to have a segmental sensory innervation. Recent studies in rats, however, have shown that the L5-L6 disc and part of the L5-L6 joint capsules are innervated by sensory neurones of the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunk, 4-10 although the fibre pathways between the disc and the sympathetic trunk are not known. Many reports have described fibres connecting the sinuvertebral nerve from the disc to rami communicantes tethered to the paravertebral sympathetic trunk, but they were thought to be sympathetic postganglionic nerve fibres. [11][12][13][14][15] Connections through the sinuvertebral nerve between the intervertebral disc and the rami communicantes have not yet been identified. We have investigated the distribution and course of both sensory and sympathetic postganglionic nerve fibres to the lumbar intervertebral disc in rats, using immunohistochemical methods. We paid special attention to the connections with rami communicantes and the segmentally corresponding spinal nerve. Materials and MethodsWe anaesthetised 17 Sprague-Dawley rats at 0 to 7 days after birth by cooling to 4°C. They were then transcardially perfused with 0.9% saline, followed by 100 ml of 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4). The spinal column with its muscles from T13 to S1 was removed, immersed in the same fixative overnight at 4°C, and then decalcified for four days in 10% ethylenediaminetetra-acetic acid (Wako Chemical, Tokyo, Japan). After storage in 0.01 M phosphate-buffered saline (PBS) containing 20% sucrose for 24 hours at 4°C, the samples were serially sectioned at 40 m in a sagittal plane on a cryostat, and the sections placed on slide glasses.Endogenous tissue peroxidase activity was...

show abstract

Section: Discussionsupporting

confidence: 62%

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes

Suseki¹,

Takahashi²,

Takahashi³

et al. 1998

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

show abstract

“…Specifically, NGFexpressing blood vessels have been detected and colocalized to sensory nerve fibers in the annulus fibrosus and the nucleus pulposus [9]. These nerve fibers are known to produce neurotransmitters, including substance P, involved in pain transmission [3]. Activated macrophages can further exacerbate the condition by triggering the release of neurotrophins and neuropeptides by neighboring macrophages and neurons [1].…”

Section: Discussionmentioning

confidence: 99%

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Veruva

Lanman

Isaza

et al. 2017

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

Background The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain.Questions/purposes The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-a (TNFa) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factorbb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation. Methods Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at 9200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p \ 0.05. Results The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFa (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFa, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFa with wear particles (p \ 0.001, q = 0.63), VEGF with macrophages (p = 0.001, q = 0.71), and NGF with blood vessels (p\0.001, q = 0.70). Of particular signif...

show abstract

“…Nerve fibres penetrate into the articular disc of the temporomandibular joint [Ichikawa et al, 1989[Ichikawa et al, , 1990Kido et al, 1993;Shimizu et al, 1996] or into the intervertebral disc of the vertebral column [McCarthy et al, 1992;Kido et al, 1993;Ashton et al, 1994]. From our previous study on the innervation of the knee joint of rats, we had evidence for penetrating of nerve fibres into the hyaline cartilage [Schwab et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

Innervation Pattern of Different Cartilaginous Tissues in the Rat

Schwab

Funk²

1998

Cells Tissues Organs

View full text Add to dashboard Cite

Background: The innervation of skeletal tissues by sensory nerves is poorly understood – especially of nerve fibres which reach into the bony and cartilaginous tissue. Methods: Samples of rat cartilaginous tissues from different locations (knee joint, vertebral column, temporomandibular joint) were fixed by perfusion and decalcified. The distribution of protein gene product (PGP) 9.5-, calcitonin gene-related peptide (CGRP)- and tachykinin (TK)-immunoreactive axons was analysed using fluorescence immunohistochemistry. Results: Nerve fibres were detected in the outer regions of the hyaline cartilage of the knee joint, in the hyaline cartilage of the vertebral body, in the fibrocartilage of the intervertebral disc and menisci, and in the articular disc of the temporomandibular joint. Predominantly, they were found to be CGRP-immunoreactive. Conclusion: The neuropeptidergic innervation of the hyaline cartilage in different locations and the presence of nerve fibres in the fibrocartilage might indicate that in addition to the classical neuronal afferent and efferent pathway these fibres may also mediate trophic actions like tissue adaptation and repair.

show abstract

Neuropeptides in the human intervertebral disc

Cited by 177 publications

References 31 publications

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Innervation Pattern of Different Cartilaginous Tissues in the Rat

Contact Info

Product

Resources

About