| Objective:A clinical and mechanistic study of Aitongping(ATP)for the treatment of cancer pain based on the guidance of Chinese medicine theory.To provide a theoretical basis for the clinical application of ATP.To explore the pathogenesis and treatment of cancer pain by combining the traditional Chinese medicine theory with the experience of modern medicine,and to provide a theoretical basis for the development of Aitongping(ATP)Capatches.And to provide a solid research basis for the treatment of cancer pain with Aitongping patches based on the exploration of the clinical application and analgesic mechanism of Aitongping patches.Methods:1.Theoretical study:Searching the literature of the past generations,through collating and analyzing,elaborating the understanding of cancer pain in Chinese medicine and modern medicine,and exploring the Chinese medical theory of cancer pain according to the theory of Chinese medicine and the clinical experience of instructors.2.Clinical study:Cases meeting the enrollment criteria were randomly divided into the Aitongping patch group and the positive opioid group with opioids alone for treatment to verify the effects of Aitongping patch on patients’ cancer pain,tumor progression,dose and side effects of strong opioid use and quality of life.3.Experimental study:A mouse model of cancer pain induced by tumor cell implantation was constructed and intervened with Aitongping patch.The sensitivity of mice to pain was observed behaviorally,and indicators such as microglia activation in the spinal cord of mice were detected.Results:1.Theoretical study:the etiology of cancer pain mainly includes six evil toxins,seven internal injuries,deficiency of positive energy,phlegm and turbidity,internal stagnation of blood stasis,and flow of cancer toxin.The location of the lesion is variable,and the internal organs involved are mainly the lung,liver and kidney;the lung and liver are mainly involved in the early stage of cancer pain,while the kidney is involved in the late stage.The treatment of cancer pain is to eliminate cancer and detoxify,remove phlegm and stasis,and relieve pain.2.Clinical research:Aitongping patch can reduce the amount of drugs used in the third stage of cancer pain treatment and effectively reduce the side effects.In addition,Aitongping patch improves patients’ emotional function and suppresses symptoms such as diarrhea and nausea,which can significantly improve patients’ survival quality.More notably,the tumor progression time of patients in Aitongping Aitongping patch group was much longer than that of the positive control drug group,which indicates that Aitongping patch has a better effect of slowing down tumor growth.3.Experimental study:We first successfully constructed a mouse model of bone cancer pain after tumor cell implantation,and confirmed the model mice were hypersensitive to acute mechanical nociception and hypersensitivity to thermal nociception through behavioral studies.We found that the expression of mouse spinal microglia marker protein Iba1 was significantly increased in the model group by Western Blot and immunofluorescence,which confirmed that cancer pain induced the activation of spinal microglia.Intervention with Aitongping patch revealed that Aitongping patch effectively relieved cancer pain in mice.Combined with FISH fluorescence and qRT-PCR,it was found that Aitongping patch promoted the expression of miR-150-5p in the spinal cord of mice and targeted the inhibition of CXCL12 expression,which in turn inhibited microglia activation.Cellular experiments revealed that primary mouse microglia activated by lipopolysaccharide showed increased expression of miR-150-5p and significantly decreased expression of downstream CXCL12 and Iba1 after intervention with Aitongping-containing serum,consistent with the results of animal experiments.Conclusion:ATP is guided by traditional Chinese medicine theory and combined with clinical reality to create a patch.Based on our research we conclude that.1.at the clinical level ATP not only improves patients’ pain but also slows down their tumour growth,reduces third-stage treatment drugs and improves their quality of life.2.At the animal level,ATP was found to be effective in relieving cancer pain in mice by inhibiting CXCL12 expression through miR-150-5p expression in the mouse spinal cord,which in turn inhibited microglia activation.3.At the cellular level,we found that ATP containing serum inhibited microglia activation by activating miR-150-5p and targeting CXCL12,and that miR-150-5p interacted with CXCL12. |