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

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. 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. The cytokines present at highest concentrations in the rat NP were TNF-alpha, IL-1 beta 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-alpha, IL-1 beta 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. 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.

Low energy elastic and electronically inelastic electron scattering from biomolecules.

Reactions initiated by collisions with low-energy secondary electrons has been found to be the prominent mechanism toward the radiation damage on living tissues through DNA strand breaks. Now it is widely accepted that during the interaction with these secondary species the selective breaking of chemical bonds is triggered by dissociative electron attachment (DEA), that is, the capture of the incident electron and the formation of temporary negative ion states [1,2,3]. One of the approaches largely used toward a deeper understanding of the radiation damage to DNA is through modeling of DEA with its basic constituents (nucleotide bases, sugar and other subunits). We have tried to simplify this approach and attempt to make it comprehensible at a more fundamental level by looking at even simple molecules. Studies involving organic systems such as carboxylic acids, alcohols and simple ¯ve-membered heterocyclic compounds are taken as starting points for these understanding. In the present study we investigate the role played by elastic scattering and electronic excitation of molecules on electron-driven chemical processes. Special attention is focused on the analysis of the in°uence of polarization and multichannel coupling e®ects on the magnitude of elastic and electronically inelastic cross-sections. Our aim is also to investigate the existence of resonances in the elastic and electronically inelastic channels as well as to characterize them with respect to its type (shape, core-excited or Feshbach), symmetry and position. The relevance of these issues is evaluated within the context of possible applications for the modeling of discharge environments and implications in the understanding of mutagenic rupture of DNA chains. The scattering calculations were carried out with the Schwinger multichannel method (SMC) [4] and its implementation with pseudopotentials (SMCPP) [5] at di®erent levels of approximation for impact energies ranging from 0.5 eV to 30 eV. References [1] B. Boudai®a, P. Cloutier, D. Hunting, M. A. Huels and L. Sanche, Science 287, 1658 (2000). [2] X. Pan, P. Cloutier, D. Hunting and L. Sanche, Phys. Rev. Lett. 90, 208102 (2003). [3] F. Martin, P. D. Burrow, Z. Cai, P. Cloutier, D. Hunting and L. Sanche, Phys. Rev. Lett. 93, 068101 (2004). [4] K. Takatsuka and V. McKoy, Phys. Rev. A 24, 2437 (1981); ibid. Phys. Rev. A 30, 1734 (1984). [5] M. H. F. Bettega, L. G. Ferreira and M. A. P. Lima, Phys. Rev. A 47, 1111 (1993).