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Experimental Studies Of The Effects Of Adriamycin With Paravertebral Injection On The Movement And Sensory Of Rats

Posted on:2008-04-08Degree:MasterType:Thesis
Country:ChinaCandidate:H L LiangFull Text:PDF
GTID:2144360215989322Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Adriamycin is an anticancer drug that is widely used in the treatment of malignant tumor.Because of its evident cytotoxicity and neurotoxicity, It can result in the degeneration of peripheral nerve. So many people take it as a classic neuropoison in animal experiment. Moreover in clinical it is used to demolish dorsal root ganglion(DRG),namely we apply this selective sensory ganglion resection to treat refractory or intractable pain.Spinal dorsal root ganglion is the important approach which the nocuous information introduces. It is the first degree neurons that the afferent sense of pain imports. The nocuous stimulation transduces in the neurons and runs the electrical signal changeover, then transfered and modulated by spinal cord, encephalic trunk and thalamencephalon. Ultimately the sense of pain produces in the cerebral cortex.DRG contains many kinds of sensory cell that hold various functions according as the size of cell. The cellule (diameter from 18 to 30μm) is sensitve to the nocuous nervous impulse and the megacell is sensitive to proprioceptive sense and touch-pressure sensation (diameter>45μm).ObjectiveObserving the effect of adriamycin on corresponding DRG cells and sciatic nerve in the aspect of Electrophysiology and pathologic after paravertebral injection with 0.33%,0.5%,1% adriamycin in rats. And Observing the effect of adriamycin on the muscle power and their active state. Exploring whether adriamycin has the function of selectively cutting off the conduction tract of pain perception and no accompanying dyskinesia of rats or not.Methods80 healthy Wister rats (weight 250-300g), were randomly divided into four groups. 0.33% adriamycin group (N1=20); 0.5% adriamycin group (N2=20); 1% adriamycin group (N3=20);physiologic saline group as control group (N4=20).After celiac anaesthesia with 3% pentobarbital (40mg/kg), the margin of right L4,L5, intervertebral foramina of the rats was exposed under the condition of sterility. Group 1, 2, and 3 were injected into the intervertebral foramina with the 10μl adriamycin at the concentration of 0.33%, 0.5%, 1% respectively. Selecting 5 rats in each group at the time of at the time of thel st, twice, 4th, 8th week respectively after paravertebral injection, the latency period and wave amplitude of the spinal motor evoked potential(SMEP),cortex sensory evoked potential(CSEP),sciatic nerve motor conduction velocity(MCV) and sensory conduction velocity(SCV),paw withdrawal latency(PWL) and the thresholds of lightning pains were measured by BL-420E biologic function experimental system and the TF-2 photothermal threshold detector.Moreover the rats's active state and the muscle power of the corresponding posterior limb of rats were evaluated according to Tarlove's grading criterion. After obtaining these Electrophysiological data, the rats were sacrificed at the second and the fourth week. Then the speciments of bilateral L4,L5 DRG and Sciatic nerve were removed to paraffin section, which stained with HE to observe morphologic change of DRG cells and sciatic nerve by light microscope. Group 4 were injected 0.9% saline into the right L4,L5 intervertebral foramina as control group.Result1. the changes of the rats's active state and the muscle powerAll of the rats had no the symptom of dyskinesia and hyperpathia before the operation. And the wound heal up all right after operation. There were no the signs of infection.During 1-8 weeks the ipsolateral posterior limbs of rats in those that were injected with 1% adriamycin displayed motor disturbance in different degree. On the base of Tarlove's Classification Measure,the grades were obviously lower than the control group. 2 in 19 rats that were injected with 0.5% adriamycin and 1 in 20 rats that were injected with 0.33% adriamycin had dyskinesia of posterior limbs. Moreover both of the concentrations appeared no statistic significance compared with the control group.2.thermal withdrawal latency (TWL)and the thresholds of lightning pains1-8 week after paravertebral injection with 1% adriamycin ,the visibly upgraded threshold value can be observed. Compared with the control group there is statistic signification(P<0.05).1 week after paravertebral injection with 0.33%, 0.5% adriamycin in rats, the thermal withdrawal latency and thresholds of lightning pains of rats degraded in different degree, conversely 2,4 and 8 week after it the threshold value visibly upgraded. There is statistic signification compared with the control group (P<0.05). 3.the changes of sciatic nerve motor conduction velocity (MCV) and sensory conduction velocity (SCV)1-8 week after paravertebral injection with 1% adriamycin in rats, the ipsolateral sciatic nerve MCV and SCV obviously slowed. There is statistic significance with group comparison(P<0.05). 1-8week after paravertebral injection with 0.33%, 0.5% adriamycin in rats, compared with the control group ,the velocity was unchanged and there is no statistic signification .(P>0.05)4.the changes of spinal motor evoked potential(SMEP)1-8 week after paravertebral injection with 1% adriamycin in rats, the latent period of SMEP largely prolonged and the amplitude of SMEP shrinked. Compared with the control group,there is statistic signification (P<0.05). However 1-8week after paravertebral injection with 0.33%,0.5% adriamycin in rats, compared with the isodose 0.9% saline group, the latent period and amplitude of MEP were unchanged. there is no statistic signification .(P>0.05)5.the changes of cortex sensory evoked potential (CSEP)1-8 week after paravertebral injection with 1% adriamycin in rats, the latent period of CSEP largely prolonged and the amplitude of CSEP shrinked. There is statistic signification by group comparison(P<0.05) . 1 week after paravertebral injection with 0.33%,0.5% adriamycin in rats, the amplitude of CSEP largely increased but the latent period didn't change. During 2-8 week both observational targets of CSEP were unchanged. The outcome compared with the control group which isodose 0.9% saline was injected had no statistic signification .(P>0.05).6. histological pathological change of DRG cells and sciatic nerveCellular necrosis were seen in DRG cells after injection 1% adriamycin at the twice and fourth week. At the fourth week, mass cellular necrosis and replacement of hyperplastic neurogliocyte and connective tissue were seen. However cellular universal degeneration were seen in the group with 0.5% adriamycin at the twice and fourth week, moreover obvious cellular necrosis in DRG were seen at the fourth week. As for the group with 0.33% adriamycin, light microscopical study of DRG sectionsrevealed hydropic degeneration, and the loss of Nissl's body at the second week. Karyopyknosis,cytoplasmic clarifixation and cellular necrosis were observed at the fourth week. Disintegrationed myelin sheath of sciatic nerve, remained necrotic contour, swollen or obsolescent neuraxis and discontinuous or obsolescent endoneurium, perineurium and epineurium were observed 2-4 weeks after injection with 1% adriamycin. 2-4 weeks after paravertebral injection with 0.5%,0.33% adriamycin and isodose 0.9% saline, we observed the similar structural feature: the size of nerve fiber were uniformity and the smaller stellar neuraxis was in the center.ConclusionThe group injected with 1% adriamycin, not only the pain sense conduction but also dynamoneure were obviously frustrated Beacause the automatic action ipsolateral posterior limbs of rats disappeared or diminished.At the same time sciatic nerve conduction velocity obviously stepped down and the evoked potentials were inhibited. Moreover there were inreversable degeneration and necrosis in the DRG and sciatic nerve. However the other two groups injected with 0.5%, 0.33% adriamycin, the evident degraded pain thresholds and the necrotic DRG can be observed. The other electrophysiologic consequences demonstrate that both of the concentrations didn't obviously damage dynamoneure.
Keywords/Search Tags:adriamycin, dorsal root ganglion, paravertebral injection, sciatic nerve, spinal motor evoked potential(MEP), sensory evoked potential(SEP), nerve conduction velocity
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