Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology

Igarashi, Tamaki; Kikuchi, Shinichi; Shubayev, Veronica I.; Myers, Robert R.

doi:10.1097/00007632-200012010-00003

Cited by 303 publications

(106 citation statements)

References 24 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

2011

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2011

View full text Add to dashboard Cite

show abstract

“…The role of TNF-a in animal models of sciatica has been documented [32]. Furthermore, Olmarker and Rydevik [33] reported the efficacy of TNF-a in preventing NP-induced functional and structural nerve root injury in animal models.…”

Section: Tumor Necrosis Factor-alpha (Tnf-a) Blockadementioning

confidence: 99%

Schmorl’s nodes

et al. 2012

View full text Add to dashboard Cite

Introduction First described in 1927, a Schmorl's node (SN) is the herniation of nucleus pulposus (NP) through the cartilaginous and bony end plate into the body of the adjacent vertebra. SNs are common findings on imaging, and although most SNs are asymptomatic, some have been shown to become painful lesions. In this manuscript, we review the literature regarding the epidemiology, clinical presentation, pathogenesis, imaging, and management of SNs. Materials and methods Using databases from the US National Library of Medicine and the National Institutes of Health, relevant articles were identified. Results While several theories regarding the pathogenesis of SNs have been proposed, an axial load model appears to have the greatest supporting evidence. Symptomatic SNs are thought to be due to the inflammatory response solicited by the herniation of NP into the wellvascularized vertebral body. Management options for symptomatic SNs vary, ranging from medical management to surgical fusion. Conclusion SNs are common lesions that are often asymptomatic. In certain cases, SNs can cause back pain. No consensus on pathogenesis exists. There is no established treatment modality for symptomatic SNs.

show abstract

“…It is suggested that the cytokine known as tumour necrosis factor a (TNFa) may be a significant player in this pathway [10]. Indeed, antibodies to TNFa are being used in clinical trials with encouraging results [11].…”

Section: Introductionmentioning

confidence: 99%

TNF?-stimulated gene product (TSG-6) and its binding protein, I?I, in the human intervertebral disc: new molecules for the disc

et al. 2004

View full text Add to dashboard Cite

Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology

Abstract: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.

Cited by 303 publications

References 24 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

Schmorl’s nodes

TNF?-stimulated gene product (TSG-6) and its binding protein, I?I, in the human intervertebral disc: new molecules for the disc

Contact Info

Product

Resources

About