| Objective By screening specific proteins of neuropathic pain induced by chemotherapy drugs(chemotherapeutic pain)in rats,the molecular mechanism of chemotherapeutic pain was discussed and analyzed,laying a theoretical foundation for the development of new targets for specific treatment of chemotherapeutic pain.Methods SD male rats were selected and intraperitoneally injected with the chemotherapy drug paclitaxel and its solvent to establish a chemotherapy pain model,which was divided into Paclitaxel(PTX)group and Vehicle group.The behavioral changes(mechanical stimulation and thermal stimulation)of rats in the two groups were detected,and the experimental results were statistically analyzed.L4-5 spinal cord tissues and dorsal root ganglion tissues of the two groups of rats were taken,and the differential proteins were analyzed and screened by tandem mass spectrometry and bioinformatic.Results The results of paw withdrawal thresholds(PWT)and paw withdrawal latencies(PWL)of the PTX group and the Vehicle group showed that,before intraperitoneal injection,there was no significant difference of the two groups of rats in the basic threshold of PWL(P>0.05).On the 4th day after intraperitoneal injection,there was no significant difference in the baseline threshold of PWT and PWL between the two groups(P>0.05);On the 7th day after intraperitoneal injection,The PWT and PWL values of the left hind paw and the right hind paw of the PTX group were significantly lower than the baseline threshold.The PWT and PWL values were significantly lower than those of the Vehicle group(P<0.05).On the 10th day after intraperitoneal injection,the PWT and PWL values of the left hind paw and the right hind paw of the PTX group continued to decrease,and were significantly lower than the Vehicle group(P<0.05).Differential protein expression in dorsal root ganglia and spinal cord tissue was analyzed using tandem mass spectrometry and bioinformatics methods.The results showed that 72 differential proteins were screened from spinal cord tissue,including 20 up-regulated proteins and 52 down-regulated proteins.The dorsal root ganglia screened for 44 differential proteins,of which 27 were up-regulated and 17 were down-regulated.According to the biological functions involved in differential proteins.G?i/o protein and AP-2 are involved in the Opioid Signaling Pathway,and Rap 1b and G?i/o proteins are involved in the Endocannabinoid Developing Neuron Pathway.Conclusions The intraperitoneal injection of the chemotherapy drug paclitaxel in rats can induce pain sensitivity reactions of mechanical stimulation and thermal radiation to the left hind foot and right hind foot,indicating that the chemotherapy pain model established by us is successful.Bioinformatics analysis showed that the expression of opioid receptor downstream protein G I/o in spinal cord was down-regulated in the opioid signaling pathway.Chemotherapeutic pain may result from hypersensitization due to activation of G?i/o coupled receptors(such as ?-opioid receptors).Therefore,G?i/o coupled protein may be a new target for the treatment of chemotherapeutic pain.Spinal cord tissue in downstream of opioid receptor protein expression AP2,research has confirmed that the AP2 neurons involved in regulating calcium ions in the steady state,the excitatory neurons cells is the basis of the electrical activity of ion channels,or can be adjusted through regulating the expression of AP2 to intracellular calcium ion transport,thus reducing the excitability of neurons,or explore the expression of certain drugs to increase AP2 raised cut,or inhibit the expression of AP2,chemotherapy to relieve or eliminate pain.Endogenous cannabinoid signaling pathway enriched ras-related protein rap-1b and G?i/o coupled proteins are down-regulated,and the combination of cannabinoid receptor CB1 and CB2 agonists can alleviate the chemotherapy pain.Therefore,specific agonists for CB1 and CB2 receptors may be developed to alleviate the chemotherapy pain. |
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