Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology: Molecular, Histologic, and Behavioral Comparisons in Rats

  title={Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology: Molecular, Histologic, and Behavioral Comparisons in Rats},
  author={Tamaki Igarashi and Shin-ichi Kikuchi and Veronica I. Shubayev and Robert R. Myers},
Study Design. This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. Objective. The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor… 

Effects of Neutralizing Antibodies to Tumor Necrosis Factor-Alpha on Nucleus Pulposus–Induced Abnormal Nociresponses in Rat Dorsal Horn Neurons

Data indicate that application of TNF&agr; antibodies to the nerve root partially prevents the nucleus pulposus–induced abnormal nociresponses and may have a therapeutic effect on sciatica after lumbar disc herniation.

Tumor Necrosis Factor-Alpha in the Nucleus Pulposus Mediates Radicular Pain, but Not Increase of Inflammatory Peptide, Associated With Nerve Damage in Mice

In this model system, TNF-α in the NP appears to mediate pain, but not cause an increase in CGRP in the DRG neurons, which is important for the production of radicular pain accompanied by long-lasting degeneration ofDRG neurons.

The Role of Tumor Necrosis Factor-&agr; in Apoptosis of Dorsal Root Ganglion Cells Induced by Herniated Nucleus Pulposus in Rats

TNF seemed to play a key role in induction of apoptosis of DRG cells, which resembled that induced by application of nucleus pulposus, and was confirmed by the presence of single-stranded DNA, Caspase 3, and TNF.

Changes in Pain Behavior and Histologic Changes Caused by Application of Tumor Necrosis Factor-Alpha to the Dorsal Root Ganglion in Rats

Because the region of the dorsal root ganglion showing the histologic changes was significantly larger after application of the higher concentration of TNF, the reaction of the DRG may be related to pain.

Exogenous Tumor Necrosis Factor-α Induces Abnormal Discharges in Rat Dorsal Horn Neurons

The possibility that TNF-alpha produced in the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain is suggested.

Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls

Its occurrence in adults of more advanced age suggests that tumor necrosis factor; is not involved in the initiation of disc degeneration, but may be associated with further promotion of degenerative disarrangement and pain induction.

Nucleus Pulposus-Induced Apoptosis in Dorsal Root Ganglion Following Experimental Disc Herniation in Rats

There were typical changes of the cell nuclei observed by light and electron microscopy, especially those of the small-sized cells, in the DRG 24 hours after application of nucleus pulposus, indicating the presence of apoptosis.

Interaction of 5-Hydroxytryptamine and Tumor Necrosis Factor-&agr; to Pain-Related Behavior by Nucleus Pulposus Applied on the Nerve Root in Rats

It is suggested that both 5-HT and TNF induce pain-related behavior and interact with each other to prolong pain- related behavior in a rat LDH model.

Sympathectomy Reduces Mechanical Allodynia, Tumor Necrosis Factor-Alpha Expression, and Dorsal Root Ganglion Apoptosis Following Nerve Root Crush Injury

Surgical sympathectomy reduced mechanical allodynia for 14 days after nerve root crush injury, and that DRG apoptosis was decreased in injured animals that underwent sympathctomy, suggesting an unknown neuroprotective effect involving interference with sympathetic activity.



Tumor Necrosis Factor α and Nucleus‐Pulposus‐Induced Nerve Root Injury

A specific substance, tumor necrosis factor α, has been linked to the nucleus‐pulposus‐induced effects of nerve roots after local application and may be of significant importance for the continued understanding of nucleus pulposus' biologic activity, and of possible potential use for future strategies in managing sciatica.

Endoneurial injection of TNF-alpha produces neuropathic pain behaviors.

The data show that subperineurial injection of TNF proximal to peripheral sensory receptors generates the transient display of behaviors and endoneurial pathologies found in experimental painful nerve injury, and implicates local TNF in the pathologies of neuropathic pain.

Reduced Hyperalgesia in Nerve-Injured WLD Mice: Relationship to Nerve Fiber Phagocytosis, Axonal Degeneration, and Regeneration in Normal Mice

Interference with the cellular mediators of Wallerian degeneration may be a useful therapeutic strategy that might modulate the onset and magnitude of hyperalgesia following nerve injury.

The Effects of Normal, Frozen, and Hyaluronidase‐Digested Nucleus Pulposus on Nerve Root Structure and Function

There was a significant reduction in nerve conduction velocity similar to previous observations when nucleus pulposus was applied just after harvest, or when it had been kept at 37 C or digested by hyaluronidase for 24 hours, however, there were no apparent differences at the histologic assessment.

Ultrastructural Changes in Spinal Nerve Roots Induced by Autologous Nucleus Pulposus

Epidural application of autologous nucleus pulposus without any pressure may induce not only nerve function impairment but also axonal injury and significant primary Schwann cell damage with vesicular swelling of the Schmidt‐Lanterman incisures.

Incision of the Anulus Fibrosus Induces Nerve Root Morphologic, Vascular, and Functional Changes: An Experimental Study

It is indicated that incision of the anulus fibrosus is sufficient to induce significant morphologic and functional changes and that vascular mechanisms may be of importance for the observed changes.

Pathomechanism of Pain‐Related Behavior Produced by Allografts of Intervertebral Disc in the Rat

The nucleus pulposus and anulus fibrosus produce different forms of hyperalgesia associated with different and distinct immunohistochemical changes, and it is possible that radicular pain of a lumbar disc herniation results from chemicals, such as phospholiapse A2 and nitric oxide.

A Controlled Immunohistochemical Study of Inflammatory Cells in Disc Herniation Tissue

The obtained results suggest a variable inflammatory cell response in DH, which seems to be often dominated by macrophages at the time of operation, and previous suggestions of sometimes very active inflammation in DH tissue are supported.