{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:35:49Z","timestamp":1792647349297,"version":"4.5.0"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Nerves and blood vessels are found in the peripheral annulus and endplates of healthy adult intervertebral discs. Degenerative changes can allow these vessels to grow inwards and become associated with discogenic pain, but it is not yet clear how far, and why, they grow in. Previously we have shown that physical disruption of the disc matrix, which is a defining feature of disc degeneration, creates free surfaces which lose proteoglycans and water, and so become physically and chemically conducive to cell migration. We now hypothesise that blood vessels and nerves in degenerated discs are confined to such disrupted tissue. Whole lumbar discs were obtained from 40 patients (aged 37\u201375\u00a0years) undergoing surgery for disc herniation, disc degeneration with spondylolisthesis or adolescent scoliosis (\u2018non\u2010degenerated\u2019 controls). Thin (5\u2010\u03bcm) sections were stained with H&amp;E and toluidine blue for semi\u2010quantitative assessment of blood vessels, fissures and proteoglycan loss. Ten thick (30\u2010\u03bcm) frozen sections from each disc were immunostained for\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    31 (an endothelial cell marker),\n                    <jats:styled-content style=\"fixed-case\">PGP<\/jats:styled-content>\n                    9.5 and Substance P (general and nociceptive nerve markers, respectively) and examined by confocal microscopy. Volocity image analysis software was used to calculate the cross\u2010sectional area of each labelled structure, and its distance from the nearest free surface (disc periphery or internal fissure). Results showed that nerves and blood vessels were confined to proteoglycan\u2010depleted regions of disrupted annulus. The maximum distance of any blood vessel or nerve from the nearest free surface was 888 and 247\u00a0\u03bcm, respectively. Blood vessels were greater in number, grew deeper, and occupied more area than nerves. The density of labelled blood vessels and nerves increased significantly with Pfirrmann grade of disc degeneration and with local proteoglycan loss. Analysing multiple thick sections with fluorescent markers on a confocal microscope allows reliable detection of thin filamentous structures, even within a dense matrix. We conclude that, in degenerated and herniated discs, blood vessels and nerves are confined to proteoglycan\u2010depleted regions of disrupted tissue, especially within annulus fissures.\n                  <\/jats:p>","DOI":"10.1111\/joa.12817","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T06:50:16Z","timestamp":1525071016000},"page":"86-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Nerves and blood vessels in degenerated intervertebral discs are confined to physically disrupted tissue"],"prefix":"10.1111","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0756-674X","authenticated-orcid":false,"given":"Polly","family":"Lama","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Le Maitre","sequence":"additional","affiliation":[{"name":"Biomolecular Sciences Research Centre Sheffield Hallam University Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Harding","sequence":"additional","affiliation":[{"name":"Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Dolan","sequence":"additional","affiliation":[{"name":"Centre for Applied Anatomy University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Adams","sequence":"additional","affiliation":[{"name":"Centre for Applied Anatomy University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2012.01551.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-198507000-00006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199602150-00006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.78B6.0780965"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200007010-00005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2674-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2675-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2016.03.019"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118884"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2004.02.011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200405150-00005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100120206"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453679408994620"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540104901210"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0416-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0889-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199072030-00013"},{"key":"e_1_2_9_19_1","first-page":"39","article-title":"The nerve supply to the human lumbar intervertebral discs","volume":"132","author":"Bogduk N","year":"1981","journal-title":"J Anat"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1097\/00007632-199512150-00002","article-title":"The diagnostic accuracy of magnetic resonance imaging, work perception, and psychosocial factors in identifying symptomatic disc herniations: 1995 Volvo Award in clinical sciences.","volume":"20","author":"Boos N","year":"1995","journal-title":"Spine"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200212010-00002"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.79B1.6814"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00080.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200207010-00006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181a01b3f"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","unstructured":"ClaxtonN FellersT DavidsonM(2010).Laser scanning confocal microscopy. 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