| Objective:In speeding recovery under the guidance of the concept of Chinese medicine acupuncture point injection and ERAS guidelines recommending multimodal analgesia,postoperative opioid save medicine principle,the principle of early postoperative recovery activities,the combination of clinical trial part design three kinds of postoperative analgesia,postoperative analgesia effect of hemorrhoid randomized controlled studies,to observe the analgesic efficacy and safety of the program,In addition,the safety and effectiveness of methylene blue,a long-acting analgesic commonly used after anorectal surgery,were preliminarily explored through basic experiments,to further rationally combine the existing analgesic methods in anorectal surgery and explore a more safe and effective multi-mode analgesic program for rapid recovery after anorectal surgery from an evidence-based perspective.At the same time,a fundamental study was designed to explore the analgesic effect and safety of methylene blue at different concentrations,which is still controversial in the scheme,to provide a reference for clinical drug use.Methods:1.Clinical researchIn A randomized controlled study,90 patients with hemorrhoids that met the criteria were randomly divided into Group A:multi-mode long-acting analgesia A;Group B:multi-mode long-acting analgesia B;Group C:multi-mode non-long-acting analgesic program C.According to different groups,the wound treatment methods of the three groups were different:methylene blue and ropivacaine were used to treat the wound in Group A.The wound surface of Group B was treated only with methylene blue.Only ropivacaine was used for wound treatment in Group C.Other analgesic measures were the same:ropivacaine injection at Yaoshu point and parecoxib sodium injection.Observe and compare the patients’ resting pain,exercise pain,defecation pain,dressing pain(VAS score),comfort(BCS score),postoperative anal edema,anal function,nausea and vomiting,urinary retention,additional analgesic drugs and other indicators at each postoperative time point.Objectively evaluate the efficacy and safety of the three groups of analgesic regimens,and provide scientific evidence-based evidence for the clinical application of ERAS multimodal long-acting analgesia regimens.2.Basic research2.1 Effects of methylene blue long-acting analgesic mixture with different concentrations on anal incision pain threshold in ratsMale SD rats were used to establish the anal incision pain model.They were divided into methylene blue low concentration group(MBA Group),methylene blue medium concentration group(MBB Group),methylene blue high concentration group(MBC Group),ropivacaine group(RO Group),and regular saline control group(NS Group).The effects of mechanical stimulus on foot contraction threshold and thermal stimulation on foot contraction reflex latency were observed through the changes in pain behavior after administration to evaluate the analgesic efficacy of different drug groups.2.2 Effects of methylene blue at different concentrations on sciatic nerve tissue in ratsMale SD rats were divided into three groups:MBA Group,MBB Group,MBC Group,NS Group,and SH Group.The changes in behavior,sciatic nerve microstructure,and related nerve molecular markers in different treatment groups at different time points were observed.2.3 Effects of different concentrations of methylene blue on rat neural Schwann cellsTaking the rat neural Schwann cell RSC96 as the research object,the effect of methylene blue on nerve cells and the possible mechanism were explored through different concentrations of administration and observation at different time points.Results:1.Clinical researchIn terms of VAS scores of postoperative resting pain and exercise pain at 24h,3d,and 5d,postoperative VAS scores of 24h,3D and 5dBCS,postoperative VAS scores of the first three times of defecation pain and dressing change,the efficacy of groups A and B was superior to Group C(P<0.05),but there was no statistical difference between groups A and B(P>0.05).The incidence of nausea and vomiting in groups A and B was lower than that in Group C.There was a statistical difference between groups A,B,and C(P<0.05),but there was no statistical difference between groups A and B(P>0.05).There were no significant differences in VAS scores of resting pain and exercise pain at 6h,7d,and 10d,BCS scores at 7d and 10d after the operation,anal edema score,and incidence of urinary retention among the three groups(P>0.05).The anal function was normal,and no anal incontinence occurred in the three groups.2.Basic research2.1 Methylene blue affected the pain behavior score of acute postoperative pain in the anal incision pain model of rats in a concentration-dependent manner:it improved the threshold of mechanical stimulation and effectively prolonged the latency of thermal stimulation.No local anal erosion necrosis and anal incontinence occured.2.2 Methylene blue caused functional damage to rat sciatic nerve in a concentration-dependent manner,which may be caused by demyelination of the nerve.The sciatic nerve tissue treated with methylene blue at different concentrations and at different time points were subjected to Masson staining and observed under the transmission electron microscope.When the concentration of methylene blue was 0.2%,the self-repairing and new regeneration of myelin was evident in the near future,but the concentration of 0.5%,1%,the short-term repair of the myelin sheath is not obvious,and the new-born myelinated nerve can be seen in the long-term.The nerve myelin sheath and axon-related molecular markers S100 and NF200 were detected by immunofluorescence,and nerve repair and regeneration could be seen in the acute phase after injury.In the long term,the content of myelin and axon-related molecular markers was negatively correlated with drug concentration.2.3 Methylene blue inhibited the proliferation of rat neural Schwann cell RSC96 cells in a concentration-dependent manner.Methylene blue administration of RSC96 cells at the same concentration showed a time-dependent trend of proliferation inhibition.The RSC96 cells after methylene blue administration were observed under an electron microscope,which showed apparent mitochondrial damage compared with normal RSC96 cells.Conclusion:1.Clinical research:Multi-mode long-acting analgesic solution A and multimodal long-acting analgesic solution B are effective for postoperative pain,resting the bandage pain,defecation pain,pain control,and the total effective rate is superior to the model more than long-term analgesia plan C,at the same time to save the application of opioid drugs,reduce the incidence of nausea and vomiting,improve patient comfort,less adverse reaction,It helps patients to move early and recover quickly.Mode long-acting analgesia plan A and B have similar efficacy,and plan B is more simplified so that multi-mode long-acting analgesia plan B may be more suitable for clinical application.2.Basic research:Methylene blue improved pain behavior scores in rats in a concentration-dependent manner and increased mechanical and thermal pain thresholds.Methylene blue solutions with concentrations of 0.2%,0.5%,and 1%caused the disintegration and stripping of the myelin sheath and axonal atrophy of the rat sciatic nerve in a concentration-dependent manner.The damage of methylene blue to nerves is reversible,nerve tissue will be slowly repaired over time,and the regeneration of damaged nerve fibers can be observed in the long term after administration.The newly formed nerve is a myelinated nerve fiber with intact myelin sheath and axonal structure.There was a negative correlation between the regeneration of nerve injury caused by the three concentrations of drug solution and the drug concentration.This may be related to the degree of nerve damage before,and there may also be different inhibitory effects of different administration concentrations on neurogenesis.This process of deterioration,repair,and rebirth of nerve fibers may lead to blockage of nerve conduction or reduced conduction function,which may be why methylene blue can relieve pain.Animal experiments did not cause a case of local tissue necrosis.Methylene blue inhibited the proliferation of rat neural Schwann cells in a time-and concentration-dependent manner,resulting in mitochondrial damage,which may cause peripheral nerve demyelination induced by methylene blue. |
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