High Levels of Inflammatory Phospholipase A2 Activity in Lumbar Disc Herniations

Saal, Jeffrey A.; Franson, Richard C.; Dobrow, Robert; White, Arthur H.; Goldthwaite, Noel

doi:10.1097/00007632-199007000-00011

Cited by 524 publications

(181 citation statements)

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“…So far the concept of chemical radiculitis is thought to be an inflammatory condition of the nerve root due to the rupture of the annulus fibrosus and dissemination of disc fluid along the nerve root sheath [24,25]. Thus, irritation of nerve roots by substances such as glycoproteins [24,25,36], immunoglobulin G [41], phospholipase A2 [45], and hydrogen ions [8,33] has been proposed.…”

Section: Development Of Chemical Rudiculitis Due To Injlummatory Cellsmentioning

confidence: 99%

Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression

Kobayashi

Yoshizawa

Yamada

2004

Journal Orthopaedic Research

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Study design: This study is to investigate the intraradicular inflammation induced by mechanical compression using in vivo model. Objectives:The relationship between the intraradicular edema and nerve fiber degeneration induced by mechanical compression was determined in the nerve root.Surnmury ofbuckground duta: Recently some studies reported that mechanical compression increased microvascular permeability of the endoneurial capillaries and resulted in an intrdradicular inflammation. These changes may be an important factor of the pathogenesis of radiculopathy. However, the natural courses of the intraradicular inflammation after mechanical compression are still poorly understood.M c h h : In dogs, laminectomy was performed at L7 and the seventh nerve root was exposed to compression at 7.5 gram force (go clipping power. The animals were evaluated at 1 and 3 weeks after clipping. After the appropriate period of nerve root compression, Evans blue albumin (EBA) was injected intravenously. The nerve root sections were divided into two groups. The sections were used to investigate the status of the blood-nerve barrier function under the fluorescence microscope. The other sections were used for light and transmission electron microscopic study.Results: After 1 and 3 weeks, intraradicular edema was observed not only at the site of compression but also in the peripheral zone of a compressed anterior root and in the central zone of a compressed posterior root. The evidence of active Wallerian degeneration was also seen in the area of intrdradicular edema. In addition, the nerve roots showing Wallerian degeneration were infiltrated by inflammatory cells, such as macrophages and mast cells.Conclusions: Inflammatory reaction, such as Wallerian degeneration, breakdown of blood-nerve barrier and appearance of macrophage, may be deeply involved in radiculitis arising from mechanical compression, and these factors seem to be important in the manifestation of rddiculopathy.

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Section: Development Of Chemical Rudiculitis Due To Injlummatory Cellsmentioning

confidence: 99%

Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression

Kobayashi

Yoshizawa

Yamada

2004

Journal Orthopaedic Research

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“…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]. In summary, the inflammatory effects induced by the contact of the NP with epidural elements are a complex event where numerous mediators and mechanisms play a role at various levels.…”

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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“…In previous studies high levels of phospholipase A 2 activity in lumbar disc herniations were measured using biochemical assessment [17,20]; however, PLA2 was not localized. In addition the authors [17,20] did not clarify whether the studied disc tissue samples contained fragments of end-plate or not.…”

Section: Discussionmentioning

confidence: 99%

“…So far only sPLA2 has been investigated in intervertebral disc tissue samples [7,10,12,20]. Some investigators suggested that herniated lumbar disc, especially in the case of sequestration, has a high PLA2 activity (sPLA2), which could be of pathophysiological importance in sciatica [17,20].…”

Section: Introductionmentioning

confidence: 99%

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Comparative immunohistochemical study of group II (synovial-type) and group IV (cytosolic) phospholipases A 2 in disc prolapse tissue

Habtemariam

Grönblad

Virri

et al. 1998

European Spine Journal

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IntroductionThe PLA2 isoforms include the secretory (also called synovial-type) group II extracellular 14 kD isoform (sPLA2) and the group IV cytosolic 85-110 kD isoforms (cPLA2) [6,21,22].It has been suggested that both types of PLA2 (sPLA2 and cPLA2) are implicated in inflammation. These enzymes catalyze the release of arachidonic acid, which is then converted, for instance, to prostaglandins by the cyclo-oxygenases (COX-1 and COX-2). Thus arachidonic acid mobilization seems to be dependent on both types of PLA2 [6,16,19,21,22].Abstract Phospholipase A 2 (PLA2) has been suggested to be present in herniated disc tissue and it could possibly be involved in sciatica/ discogenic back pain mechanisms. In the present study the occurrence of two different phospholipase A 2 enzymes, (1) low molecular weight (14 kDa) group II synovial-type (sPLA2) and (2) high molecular weight (85 kDa) group IV cytosolic (cPLA2), were compared. Fifty-three disc prolapses obtained at disc operations were analyzed by immunohistochemistry, using anti-human monoclonal antibodies to sPLA2 and cPLA2, respectively. Only cell-associated (disc cells, hyaline cartilage chondrocytes) sPLA2 and cPLA2 immunoreactivity could be observed. The results showed that sPLA2 was more common (25/53, 47%) than cPLA2 (13/53, 25%). sPLA2 and cPLA2 were simultaneously present in 13 of 53 samples (25%). However, both PLA2 enzymes were predominantly present in hyaline cartilage cells (sPLA2: 16/53, cPLA2: 5/53), being less commonly observed in disc cells (sPLA2: 6/53, cPLA2: 3/53). In addition, three samples for sPLA2 and two samples for cPLA2 exhibited immunoreactivity in cartilage and disc cells simultaneously. sPLA2 was observed in no other locations, but in 3 of 53 samples cPLA2 was observed more diffusely in areas of granulation tissue, possibly in macrophages. No gender-or age-related dependence for either type of PLA2 enzyme immunoreactivity could be observed. Neither did their occurrence relate to clinical data such as straight leg raising or neurological deficit. The results do not support a major role for either of the two disc-cell-associated PLA2s in disc pathophysiology. For both enzymes, the major pool appears to reside in cartilage tissue cells, presumably in dislodged end-plate fragments. Disc cells are apparently unlikely candidates for major PLA2 storage.

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High Levels of Inflammatory Phospholipase A2 Activity in Lumbar Disc Herniations

Cited by 524 publications

References 0 publications

Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression

Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression

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

Comparative immunohistochemical study of group II (synovial-type) and group IV (cytosolic) phospholipases A 2 in disc prolapse tissue

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