The Implication Of The Expression Of TNF-α And It's Releasing Proteases In DRGs Derived By Atuo-transplantation Of Nucleus Pulposus And The Effect Of The Pentoxifylline

Objectives. The low back and/or sciatic pain is one of the mainly health problems that nearly all contries are facing. The inflammation caused by herninated intervertebral disc has been suggested to play an important role in the mechanism of radicular pain.The previous studies have shown that nucleus pulpusus may induce structural and functional changes in nerve roots,such as the compartment syndrome in the dorsal root ganglion ,the endoneurial edema,the increasement of the endoneurial fluid pressure and the reduction of intraneural blood flow.The nucleus pulposus contains many pro-inflammatory cytokines,tumor necrosis factor-alpha is thought to be a key pathogenic factor in the initiation and maitenance of neuropathic pain.we use an animal model of herniated nucleus pulposus to investigate the expression character of TNF-α, TNFR-Ⅰ, MMP-9 and TACE in the DRG.s and NRs, to analysis the relationship between the expression of TNF-αand it's releasing proteases and the pain-related behaviors.In addition the effects of pentoxifylline on the changes of histology of DRGs and pain-related behaviors are evaluated.Methods. Autologous nucleus pulposus was applied to the peripheral of the L4 and L5 nerve roots and DRGs .Based on this animal model,Von Frey filaments and a thermal testing device (RTX-1 type) was used to quantify behavior test. Hemattoxylin and eosin staining,Toluidne blue staining and electron microscope was used to observe the histologic changes of DRGs.Immunocytochemistry and reverse transcription polymerase chain reaction was used to find out the expression changes of TNF-α,TNFR-Ⅰ,MMP-9,TACE.By a epidurale catheter PTX was injected into the positon of the L4 and L5 nerve roots and DRGs,the changes of hitologic and pain-related behaviors were recorded. Results. 1.Peripheral applying of the nucleus pulpusus to NR and DRG caused obviously mechanical allodynia ,but thermal hyperalgesia was not oberserved.Significant endoneurial edema ,inflammation reaction and demyelination can be seen in the DRGs and NRs.2.The protein expression of TNF-α, TNFR-Ⅰ, MMP-9 and TACE were upregulated in DRGs ,nerve roots and dosal horn. Similar spatial and time distributing patterns werepresented.3.The expression of TNF-αmRNA and TACE mRNA was upregulated after nucleus pulposus implanted . Increasing level of TNF-αmRNA was corresponding to the presence of mechanical allodynia .4.PTX could diminish the inflammation reaction and improve the degree of mechanical allodynia.Conlusions. Endogenetic TNF-α was involved the mechanism of mechanical allodynia after autologous nucleus pulposus implanted. MMP-9 may be associate with the damage of blood nerve barrier(BNB) and was helpful to the releasing of TNF-α. TACE caused the shedding of the active TNF-α from cell membrane,it's a new therapy target to inhibit the action of TNF-α.PTX ,as an anti- TNF-α drug, could diminish the degree of mechanical allodynia caused by topical application of NP,which suggested that anti-inflammatory cytokine therapy,especially to TNF-α, may become an effective treament of sciatica due to disc herniation.