Murine Nucleus Pulposus-Derived Cells Secrete Interleukins-1-β, -6, and -10 and Granulocyte-Macrophage Colony-Stimulating Factor in Cell Culture

Rand, Nahshon; Reichert, Fanny; Floman, Yizhar; Rotshenker, Shlomo

doi:10.1097/00007632-199711150-00002

Cited by 147 publications

(85 citation statements)

References 33 publications

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“…However, the concentration of IL-6 in the normal intervertebral disc was similar to adipose tissue. Although cytokines were found in large quantities in herniated nucleus pulposus [26,27], it was unclear whether the cytokine secretion would be derived from inflammatory cells that infiltrated the herniated nucleus pulposus tissue or from disc-derived cells. 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].…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…This phenomenon, known as hyperalgesia, is a common denominator of all inflammatory processes and is characterized by the decrease in the nociceptive threshold and increased activity in response to thermal and mechanical stimulation [15]. The role of local cellular mediators such as cytokines and chemokines in the inflammatory hyperalgesia was extensively studied and there is no doubt nowadays about their involvement in the etiology of the painful sensitization after tissue damage [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2011

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“…Application of nucleus pulposus onto nerve roots has been shown to induce edema of the nerve roots and dorsal root ganglia, and to alter the conduction velocity [41]. Proinflammatory cytokines, including IL-1, IL-6, and TNF-alpha, as well as COX-2, are known mediators of the peripheral inflammatory response caused by nucleus pulposus [10,28,30,36]. These molecules are also synthesized and released during various types of nerve injury [26].…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model

et al. 2009

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Nuclear factor-kappa B (NF-jB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-jB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-jB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation ? decoy group, a herniation ? oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-jB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation ? decoy group than in the other herniation groups.Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation ? decoy group. NFjB decoy was transduced into DRGs in vivo. NF-jB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.

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“…These substances have also been found to be elevated in patients with viral and bacterial infections [3,16,19]. Interestingly, the proinflammatory cytokines interleukin 1 and 6 have been detected at increased concentrations after stimulation of intervertebral murine disc cells with the bacteria Escherichia coli [28].…”

Section: Introductionmentioning

confidence: 99%

Detection of bacterial DNA in painful degenerated spinal discs in patients without signs of clinical infection

2004

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A local inflammatory and potentially painful response, of which the ultimate cause is unknown, has been described in nervous tissues in contact with degenerated disc material in patients with low back and leg pain. With the rationale that a possible cause of such inflammation could be bacterial infection, we utilized PCR (polymerase chain reaction) amplification of the 16S rRNA (ribosomal RNA) gene followed by gene sequencing, to investigate whether bacterial DNA might be detected in the degenerative discs of 10 patients operated for disc herniation or post-discectomy syndrome. One patient with disc hernia harbored DNA homologous to Bacillus cereus, and in one patient suffering from post-discectomy syndrome, Citrobacter braakilfreundii DNA was detected. The finding demonstrates that 16S rRNA PCR can be a useful tool in search of bacterial DNA in degenerated discs, which in turn may be indicative of low-grade infection, manifesting itself only as pain rather than as clinical infection.

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Murine Nucleus Pulposus-Derived Cells Secrete Interleukins-1-β, -6, and -10 and Granulocyte-Macrophage Colony-Stimulating Factor in Cell Culture

Abstract: Cultured murine disc-derived cells have the capacity to secrete proinflammatory cytokines and interleukin-10 in the absence of inflammatory cells. This finding supports the hypothesis that disc-derived cells are capable of initiating or amplifying an inflammatory process.

Cited by 147 publications

References 33 publications

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

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

Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model

Detection of bacterial DNA in painful degenerated spinal discs in patients without signs of clinical infection

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