Effects of Steroid and Lipopolysaccharide on Spontaneous Resorption of Herniated Intervertebral Discs

Minamide, Akihito; Tamaki, Testuya; Hashizume, Hiroshi; Yoshida, Munehito; Kawakami, Mamoru; Hayashi, Nobuhiro

doi:10.1097/00007632-199804150-00007

Cited by 107 publications

(94 citation statements)

References 28 publications

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“…These limitations are well recognized in histologic studies of human intervertebral discs. Disc fixation, decalcification, and slide preparation in this study followed guidelines published for previous intervertebral disc studies 20,34–36 …”

Section: Discussionmentioning

confidence: 99%

Micromorphometry and Cellular Characteristics of the Canine Cervical Intervertebral Discs

Johnson

Costa

Allen

2010

Journal of Veterinary Internal Medicine

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Background: Dogs have a high prevalence of disc-associated cervical spinal cord disorders. Despite this, there are no descriptions of the micromorphometry or cellular characteristics of canine cervical intervertebral discs.Hypothesis Animals: Six CH dogs and 6 NCH dogs, under 3 years old.Methods: Histologic sections of all cervical discs from each dog were examined. Micromorphometric variables included relative ratio of ventral to dorsal annulus fibrosus (AF), number and mean width of AF fibers, and relative percentage of NP. Cellular variables included cell density, morphology, and grouping.Results: The NP from CH dogs was smaller, more rounded, and more dorsally located compared with that from NCH dogs. The NP occupied a greater proportion of the disc in NCH dogs compared with CH dogs (27.7 versus 15.8%; P o .001). The ratio of ventral to dorsal AF was approximately 3 : 1 in the CH group and 2 : 1 in the NCH group. Cellular variables were region dependent. Cell density was 2.4-fold higher in the OA compared with the NP. Approximately 50 of NP cells and 4.5% of OA cells occurred in groups.Conclusions and Clinical Importance: Micromorphometric variables differed by CH status. Cellular variables differed by disc region. Our findings potentially can explain the high incidence of intervertebral disc extrusions in CH dogs compared with NCH dogs.

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Section: Discussionmentioning

confidence: 99%

Micromorphometry and Cellular Characteristics of the Canine Cervical Intervertebral Discs

Johnson

Costa

Allen

2010

Journal of Veterinary Internal Medicine

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“…HD occurs when the disc protrudes into the epidural space or neural foramina and causes mechanical deformation of nerve tissues inducing severe pain [ 19,20,27]. Histologically HD is surrounded by granulation tissues characterized by inflammatory cell infiltration and newly formed vessels [ 10,11,17]. These -"Presented at the 49th Annual Meeting of the Orthopaedic cells express the matrix metalloproteinase (MMP)-3 and MMP-7 [7,11,22].…”

Section: Introductionmentioning

confidence: 99%

Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the Herniated disc

Kato

Haro

Komori

et al. 2004

Journal Orthopaedic Research

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Intervertebral disc herniation (HD) is one of the most common orthopaedic conditions. MRI analysis of H D has revealed a spontaneous resorption mechanism related with neo-vascularization. It appears that the interaction of activated macrophages with disc tissues leads to the generation of inflammatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-a (TNF-a) is required for the induction of angiogenesis inducing factors such as vascular endothelial growth factor (VEGF) or matrix degrading enzymes such as MMP-3, MMP-7 and plasmin. We hypothesized that these molecules play a crucial role during spontaneous H D resorption. In this study, we have examined the sequential expression of these molecules using a co-culture system which is composed of the interaction of activated macrophages and disc tissues as a model of the acute response of inflammation occurred in HD. We have also considered the mechanism of activating latent MMPs during H D resorption process. Current our results indicate that upregulation of both TNF-cl mRNA and protein expressions occur first in the inflammation induced by HD. VEGF upregulation follows the increased level of TNF-a expression. Both plasmin and MMP-3 are upregulated at later time points. We also demonstrate that both TNF-a and VEGF induce upregulated expression of urokinase-type plasminogen activator (u-PA). Our previous work has demonstrated that TNF-(r could upregulate the expression of VEGF, MMP-3 and MMP-7 in the co-culture system. It has been reported that plasmin could affect to activate latent MMPs. Based on these findings, we suggest that TNF-a acts as the initiator of inflammation following contact between macrophages and disc chondrocytes and that plasmin and u-PA play a crucial role in activation of MMPs. We propose a spontaneous H D resorption cascade. Further understanding of the resorption process may provide future novel therapies for HD.

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“…Long‐term results of surgery are not different from conservative treatment for radicular pain, and although epidural injections can be effective in 80% of cases, patients often need four to five injections within a year . Moreover, steroids might slow down the natural resorption of extruded NP tissue as shown in a rabbit tissue model . Reducing pain, while not inhibiting resorption, would be a promising approach to treat herniation.…”

mentioning

confidence: 99%

Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX‐2‐specific inhibitor

Dijk

Potier

Dijk

et al. 2015

Journal Orthopaedic Research

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In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained-release cyclooxygenase-2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained-release. Swelling explants produced elevated levels of interleukin-6 (IL-6) and prostaglandin E 2 (PGE 2 ) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE 2 production, but did not affect IL-6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation.

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Effects of Steroid and Lipopolysaccharide on Spontaneous Resorption of Herniated Intervertebral Discs

Cited by 107 publications

References 28 publications

Micromorphometry and Cellular Characteristics of the Canine Cervical Intervertebral Discs

Micromorphometry and Cellular Characteristics of the Canine Cervical Intervertebral Discs

Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the Herniated disc

Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX‐2‐specific inhibitor

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