An Experiment Research Of The Expression Of GDNF In DRGs Derived By Auto-transplantation Of Nucleus Pulposus And The Relationship Between The Hyperalgesia And GDNF

Herniated intervertebral disc does an injury to the nerve roots in two ways. They are mechanical pressure and inflammation. In recent years, the relationship between the nucleus pulposus and hyperalgesia has been widely concerned. It has been proved that without mechanical pressure the nucleus pulposus alone can make the dorsal root ganglion (DRG) induce morphological and hemodynamical changes. In addition, it increases the excitability of the neurons in the DRGs and makes them present ectopic discharge which is associated with hyperalgesia. But the mechanism of the hyperalgesia induced by nucleus pulposus is still not completely understood.It is widely believed that the basically reason of pain disorders is the ectopic discharge derived by injury to the nerves. And the ectopic discharge is the result of ectopic presentation of the ionic channels and receptors. Most of the researchers believe that inflammatory reaction derived by nucleus pulposus is the reason of hyperalgesia. But after the inflammatory reaction takes place there must be ectopic presentation of the ionic channels and receptors produced by injured neurons which induces ectopic discharge and hyperalgesia. It is not clear now how inflammatory reaction makes the neurons presence ionic channels and receptors abnormally. In recent years, many researchers begin to pay attention to the role of glial cell line-derived neurotrophic factor(GDNF) in this course. They guess that GDNF up-regulates the expression of the ionic channels and receptors which induces ectopic discharge and hyperalgesia. To improve this hypothesis we must make sure that the expression change of GDNF in DRGs is related to hyperalgesia.In this study, we harvest the nucleus pulposus from the tails of rats and transplant it to the peripheral of the same rat's lumbar nerve roots . Based on this animal model, usingbehavior test﹑hematoxylin and eosin(HE) staining﹑electron microscope ﹑immunocytochemistry(ICC)﹑immunofluorescence﹑reverse transcription polymerase chain reaction(RT-PCR), we try to find out hyperalgesia induced by nucleus pulposus and the harmful effects on DRGs and the relationship between them. We also research about the expression change of GDNF in DRGs and the relationship between the hyperalgesia and the change of the endogenetic GDNF in DRGs. The main results and conclusions are as follows:1. Peripheral apply of the nucleus pulposus to rat's lumbar nerve roots results in hyperalgesia of related hindlimb.2. Nucleus pulposus alone can injury the DRG. Edema and ultrastructure morphological changes can be found. And these changes are related to hyperalgesia.3. GDNF,GDNFR-αand Ret are mainly distributed in the medium and small neurons in DRG which indicates GDNF perhaps takes part in the regulation of pain.4. Production of the protein and mRNA of GDNF is all up-regulated after nucleus pulposus transplantation.Increasing level of the GDNF expression is corresponding to the presence of hyperalgesia which strongly indicates in molecular level that GDNF is involved in the regulation of pain.