Herniated Lumbar Intervertebral Discs Spontaneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin-6, and Prostaglandin E2

Kang, James D.; Georgescu, Helga I.; McIntyre-Larkin, Lori; Stefanović-Račić, Maja; Donaldson, William F.; Evans, Christopher H.

doi:10.1097/00007632-199602010-00003

Cited by 566 publications

(303 citation statements)

References 39 publications

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“…These findings were subsequently confirmed by another study with histological examination in ten patients who underwent anterior fusion for severe pain [33]. One can speculate that the MRI vertebral body type 1 inflammatory changes may be due to vertebral endplate discontinuities, which may then allow inflammatory mediators from the disc [15,16,23,25,28,32] to act upon the adjacent vertebral body.…”

Section: Discussionmentioning

confidence: 75%

Vertebral body MRI related to lumbar fusion results

et al. 1997

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The evaluation of continued pain after a technically successful posterolateral lumbar spine fusion is often challenging. Although the intervertebral disc is often a source of low back pain, abnormal endplates may also be a focus of pain, and possibly a source of continued pain after a posterolateral fusion. MRI allows noninvasive evaluation for disc degeneration, as well as for abnormal endplates and adjacent vertebral body marrow. Previous studies have found inflammatory marrow changes, adjacent to abnormal endplates, associated with disc degeneration in low back pain patients. In this study, preoperative MRI scans in 89 posterolateral lumbar fusion patients were reviewed, by an independent radiologist, to determine whether vertebral body marrow changes adjacent to the endplates were related to contined pain. Independent chart review and follow-up telephone interview of all patients at a 4-year follow-up (mean) formed the basis for the clinical results. Vertebral body MRI signals consistent with inflammatory or fatty changes were found in 38% of patients, and always occurred adjacent to a degenerated disc. Inflammatory MRI vertebral body changes were significantly related to continued low back pain at P = 0.03. We conclude that posterolateral lumbar fusion has a less predictable result for the subset of degenerative disc patients with abnormal endplates and associated marrow inflammation. More research is needed to determine the biological and biomechanical effects of a posterolateral fusion upon the endplate within the fused segments. If indeed further study supports the hypothesis that abnormal endplates associated with inflammation are a source of pain, then treating the endplates directly by anterior fusion may be a preferred treatment for this subset of degenerative patients.

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Section: Discussionmentioning

confidence: 75%

Vertebral body MRI related to lumbar fusion results

et al. 1997

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“…Previous reports showed proinflammatory cytokines such as IL-1b, IL-6, and TNF were expressed in human herniated disk specimens [8,28]. Intervertebral disk cells may produce TNF-a, IL-1b, and monocyte chemoattractant protein-1 immediately after the onset of disk herniation [32].…”

Section: Discussionmentioning

confidence: 94%

“…The highest possible JOA score-L is 29 points. The mean JOA score-L was 12.4 points (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. To evaluate the relationships between neurological deficits and the concentrations of the cytokines, the sum of motor disturbance and the sensory disturbance of JOA score-L (neurological deficits score) was calculated.…”

Section: Methodsmentioning

confidence: 99%

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

et al. 2009

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There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders. This study investigated whether interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) could be detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines correlated with the severity of disease conditions. CSF samples were obtained from 21 patients with cervical myelopathy (Group M) and 19 patients with lumbar radiculopathy (Group R), and six volunteers (control). The concentration of IL-6 was significantly higher in Groups M and R than in the control, possibly demonstrating spinal cord and nerve root damage, respectively. However, TNF-a was lower than the detection limit. IL-1b was detected in only five samples from three patients in Group M and two volunteers in the control. The concentrations of IL-6 did not show any correlation with symptom duration, the scoring system by the Japanese Orthopaedic Association, or the duration of nerve root block. There is a possibility that the concentration of inflammatory cytokines in CSF can indicate certain pathological aspects of cervical myelopathy or lumbar radiculopathy.

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“…The capacity of normal disc cells to secrete proinflammatory cytokines and interleukin-10 in the absence of inflammatory cells was observed in cultured murine disc [28]. TNF-a is spontaneously produced by intervertebral disc tissue in culture, and it has been found in the NP cells of rats and pigs [8,18,27]. In herniated disc, TNF-a is expressed at higher levels compared to asymptomatic or autopic controls [29].…”

Section: Discussionmentioning

confidence: 99%

“…The NP structure mainly comprises proteoglycans, collagen and support cells, which are able to produce inflammatory mediators after injury, such as cytokines [7]. In fact, these elements may be involved in the effects observed in clinical experimental models of back pain [7][8][9]. Besides locally produced cytokines, immunoglobulins (IgG, for instance), hydrogen, nitric oxide (NO) and enzymes such as phospholipase 2 (PLA2) might be responsible for the pathophysiological reactions [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

2011

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Introduction The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Material and methods Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. Results The cytokines present at highest concentrations in the rat NP were TNF-a, IL-1b and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-a, IL-1b and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Conclusion Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

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Herniated Lumbar Intervertebral Discs Spontaneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin-6, and Prostaglandin E2

Cited by 566 publications

References 39 publications

Vertebral body MRI related to lumbar fusion results

Vertebral body MRI related to lumbar fusion results

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

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