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

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Abstract

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-α, IL-1β 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-α, IL-1β 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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Acknowledgments

We thank Ieda Regina dos Santos Schivo and Sérgio Roberto Rosa for technical assistance during the behavioral tests. Research supported by grants from Fundação de Amparo à Pesquisa de São Paulo (FAPESP, Brazil), Pronex, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil). No benefits were received and there is no disclosure to be presented by the authors.

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Authors and Affiliations

  1. Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 11° andar, Ribeirão Preto, São Paulo, 14048-900, Brazil

    André Luiz de Souza Grava & Helton L. A. Defino

  2. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Luiz Fernando Ferrari

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  1. André Luiz de Souza Grava
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Correspondence to Helton L. A. Defino.

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de Souza Grava, A.L., Ferrari, L.F. & Defino, H.L.A. Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus. Eur Spine J 21, 537–545 (2012). https://doi.org/10.1007/s00586-011-2027-8

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