| BackgroundCatheter-related bladder discomfort(CRBD),an extremely distressing complication caused by an indwelling urinary catheterization,is frequently reported postoperatively in patients undergoing transurethral resection of the prostate(TURP).People with CRBD frequently reported postoperative urethral pain,frequent urination,urgency,and behavioral reactions,as well as attempts to pull out the catheter.CRBD is a very unpleasant clinical complication that increases the chance of postoperative adverse reactions.Because of various mechanical pulls and inflammation,visceral afferent sensory nerve sensitivity increased,resulting in involuntary contraction of the bladder detrusor muscle and bladder stimulation symptoms.It suggests that one of the mechanisms of CRBD is the transmission of bladder visceral sensory nerve signals.Methods to relieve CRBD due to drug side effects and the painful process of nerve block that reduces the comfort of medical treatment.Transcutaneous electrical acupoint stimulation(TEAS)is a method based on acupuncture that draws lessons from traditional Chinese medicine.The output end is changed to an electrode patch,and a current loop is formed between the two electrode patches,which has the same effect as acupuncture acupoints.TEAS is found to have the characteristics of improving postoperative discomfort in clinical,such as reducing systemic itching in uremia patients,reducing cough response in patients with soft bronchoscopy,and alleviating postoperative fatigue.The selection of acupoints is especially important in the TEAS."Zhongji","Yinjiao" and "Ciliao" acupoints are effective in the treatment and prevention of urogenital diseases.In animals,meridians and acupoints exist in the same way that they do in humans.Animal experiments showed that acupoint electrical stimulation can relieve the occurrence of visceral pain.The bladder’s afferent nerves can produce transmitters such as the calcitonin gene-related peptide(CGRP).CGRP is a nociceptive marker that is abundant in C visceral sensory afferent fibers in the bladder.By changing neuronal excitability,CGRP can mediate pain sensitization,deliver pain stimulation signals to the spinal cord,and activate the PI3K/AKT pathway.AKT(protein kinase B),a P13K(Phosphatidylinositol 3-Kinase,PI3K)substrate,modulates intracellular signaling in nociceptive information in the spinal cord and has been reported in peripheral neuralgia or visceral pain,demonstrating that AKT can initiate peripheral sensitization and hyperalgesia responses.According to research,acupoint electrical stimulation has neuromodulator effects,which can regulate the expression of nociceptive neurotransmitters and inhibit pain signaling.We designed this topic based on the above theory,with the first part aiming to reveal the effect of TEAS on CRBD,and the second part aiming to mimic bladder stimulation symptoms in overactive bladder rats,investigate the reduction of visceral pain by inhibiting the PI3K/AKT pathway,and provide guidance for the mechanism of CRBD.PART Ⅰ.Transcutaneous electrical acupoint stimulation relieve postoperative catheterrelated bladder discomfort in patients undergoing transurethral resection of the prostateObjectiveObserve the clinical effect of TEAS pretreatment on the incidence and severity of postoperative CRBD in patients with TURP.Methods1.Ethics approval and RegistrationThis study was approved by the Clinical Research Ethics Committee and registered by the China Clinical Trial Center with patients’ informed consent.2.Grouping,acupoint selection and treatmentIn this study,80 patients who underwent benign prostatectomy were enrolled.The TEAS group received preoperative TEAS at 2/100 HZ,the strength of which is determined by the patient’s conscious comfort,for 30 minutes.The control group used the same electrode site but did not energize it."Yinjiao","Zhongji" and bilateral "Ciliao" acupoints were chosen.Due to changes in surgical procedures and postoperative follow-up damage,70 patients were finally included in the statistical analysis.3.Intraoperative and postoperative treatmentAll patients have been monitored of perioperative vital signs under general anesthesia with the same surgeon during the operation of TURP.To prevent postoperative nausea and vomiting(PONV),the surgery was ended with an intravenous injection of ondanstetron.Intermittent administration of sulfentanyl injection during the operation and fluorbiloprofen injection were given once postoperatively,and the surgeon was informed to routinely administer analgesic drugs,and the drug name and number of times were recorded.4.Observation index and observation momentThe main observative indicators of this study:to assess the incidence and severity of CRBD at the end of operation(T1),out of post anesthesia care unit(PACU)(T2),24 hours after operation(T3)and 48 hours after operation(T4),respectively.Secondary observations in this study:(1)40-items Quality of Recovery questionnaire(QoR-40)were assessed for patients at the time of preoperative(T0),24 hours(T3)and 48 hours(T4)after surgery.(2)Sedation scale was assessed for patients at the end of the operation(T1),out of PACU(T2),24 hours after surgery(T3)and 48 hours after surgery(T4).(3)Mini-mental status estimate(MMSE)was assessed for patients at the time of the preoperative(T0),out of PACU(T2),24 hours after operation(T3)and 48 hours after the surgery(T4).(4)Postoperative pain,and postoperative nausea and vomiting(PONV)were assessed for patients at the time of end of the operation(T 1),out of PACU(T2),24 hours after operation(T3)and 48 hours after operation(T4),Verbal rating system(VRS)was used to assess postoperative pain,and the nausea verbal descriptive scale(NVSD)was used to assess PONV.(5)Laboratory indicators were assessed for patients at the time of before the surgery,30 minutes after the surgery,end of the surgery,out of PACU and 2 hours after the surgery(serum TNF-α,IL-1β,β-endorphins,arterial blood glucose concentration and lactate concentration).Results(1)There were no significant differences in age,height,body weight,body weight index(BMI),anesthesia and surgical time,intraoperative,sulfentanyl,propofol,refentanyl,cisatracamonium,and liquid consumption between the two groups(P>0.05).(2)CRBD comparison between two groups:At the time of T1,T2,T3,and T4,the total incidence of CRBD was significantly lower in the TEAS group than in the control group(P<0.05).At the time of T1,T2,and T3,the incidence of moderate to severe CRBD was significantly lower in the TEAS group than in the control group(P<0.05).(3)Comparison of total score of QoR-40 between two groups:The QoR-40 total score was higher in TEAS group at the time of T3 and T4(P<0.05).(4)Postoperative pain comparison in two groups:there was no significant difference in VRS scores between the two groups.The total number of postoperative analgesic drug uses in the control group was significantly higher than in the TEAS group during the follow-up period(P<0.05).Parecoxib sodium injection,pentazocine injection,and indometacin suppositories were used by both groups.The use of parecoxib sodium injection was significantly higher in the control group than in the TEAS group(P<0.05).(5)Comparison of PONV in two groups:there was no significant difference in two groups with PONV incidence(P>0.05).(6)Ramsay sedation scores in two groups:there was no significant difference in sedation scores between the two groups(P>0.05).(7)Comparison of MMSE in two groups:it was significantly lower MMSE scores at the time T2 than at the time T0,T3 and T4 in each group.However,MMSE scores between the two groups were not statistically significant(P>0.05).(8)Laboratory indicators:arterial blood glucose concentrations in both groups gradually increased after PACU and 2 hours after surgery,but there was no statistically significant difference between the two groups(P>0.05).There was no significant difference in serum IL1β,TNF-α,β-EP,or arterial blood lactate concentrations in two groups(P>0.05).ConclusionsTEAS can significantly reduce the incidence of postoperative CRBD and reduce the CRBD severity in patients with TURP.PART Ⅱ.PI3K/AKT participates in the study of electroacupuncture to relieve rat bladder visceral painObjectiveA model of rat bladder detrusor overactivity was established to explore the effect of acupoint electrical stimulation to inhibit the PI3K/AKT pathway in relieving visceral pain.Methods1.Animal’s preparationMale SD rats weighing 220-290g were assigned at random to one of three groups:control,model,or EA group(n=7).Control group:A cystostomy was performed on the control group,followed by 60 minutes of saline perfusion at 0.1ml/min micropump speed for urodynamic testing.Model group:rat bladder perfused with saline for 60 minutes(before modulation)for the first urodynamic testing,then 0.25%acetic acid for 60 minutes,then saline for another 60minutes(after modulation)for the second urodynamic testing.EA group:saline perfusion for initial urodynamic testing(before EA treatment),followed by EA treatment with 30min before bladder perfusion with 0.25%acetic acid for 60 minutes,and urodynamic data were measured with saline for another 60 minutes(after EA treatment)for the second urodynamic testing.2.Acupoints selectionAcupoints selected "zhongji"(straight prick about 5mm),"Guanyuan"(straight prick about 2mm)and bilateral "ciliao" acupoint(straight prick about 15mm).EA parameter is following as:2/100HZ,intensity is about 1mA,for 30 minutes,it is appropriate to take the rat tail fibrillation.3.Index detection(1)The physiological signal acquisition and processing system detects rat urodynamic data(voiding interval time,basal urination pressure,maximum bladder detrusor pressure,bladder capacity,and mean urine urination pressure)and bladder detrusor EMG discharge amplitude.(2)qRT-PCR for detecting AKT-mRNA level in the spinal cord(L5-S1).(3)Western blot examined the expression levels of CGRP in DRG(L5-S1),AKT、p-AKT and PI3K protein in spinal cord(L5-S1)and bladder detrusor cholinergic M3 receptor.(4)Elisa was used to test rat bladder detrusor Ach content and serum IL-1 β,TNF-α values.Results1.Comparison of urodynamic parameters:There is no significant difference in urodynamic parameters in groups prior to modulation(P>0.05).Rats in the model group had significantly shorter urine intervals,higher basal urine pressures,lower maximum bladder detrusor pressures,and lower bladder capacity when compared to the control group(P<0.05).Rats in the EA group had a longer urination interval,lower basal urination pressure,increased bladder capacity,and higher maximum bladder detrusor pressure than rats in the model group(P<0.05).Urodynamic parameters in the model group rats differed statistically significantly before and after modulation(P<0.05).In the EA group,there was no comparison of rats before and after EA treatment(P>0.05).2.Comparison of bladder EMG amplitude:There was no significant difference between the bladder EMG amplitude before modulation(P>0.05).The model group’s amplitude was significantly reduced when compared to the control group(P<0.05),whereas EMG amplitude was significantly increased in the EA group(P<0.05).In the model group,there was a significant difference in contrast before and after modulation(P<0.05).There was no significant difference between rats before and after EA treatment in the EA group(P>0.05).3.Comparison of bladder Ach content and M3 receptor expression:When compared to the control group,the bladder Ach content was significantly higher in the model group(P<0.05),as was cholinergic receptor M3 protein expression(P<0.05).The rat bladder Ach content was significantly lower in the EA group(P<0.05)compared to the model group,while the expression of the cholinergic receptor M3 protein was higher(P<0.05).4.Comparison of CGRP expression in spinal ganglia:CGRP protein expression in spinal ganglia was significantly increased vs control group(P<0.05);Compared to the model group,CGRP protein expression levels decreased in EA group(P<0.05).5.AKT,p-AKT and PI3K protein expression(1)p-AKT:Compared to the control group,the spinal p-AKT protein expression level increased but not statistically significant(P>0.05);the spinal p-AKT protein level in the EA group was significantly decreased compared to the model group(P<0.05).(2)Western blot showed that there was no significant difference between total AKT protein expression(P>0.05).qRT-PCR detection showed the difference was not statistically significant in groups(P>0.05).(3)PI3K:Spinal PI3K protein expression increased in the model group(P<0.05)and significantly decreased after electroacupuncture pretreatment compared with model group(P<0.05).6.Comparison of laboratory indicators in groups:Compared with the control group,serum IL-1 and TNF-levels increased significantly in the model group(P<0.05),whereas in the EA group showed significantly decrease of IL-1 and TNF-levels(P<0.05).ConclusionsAcupressure electrical stimulation reduces bladder hyperactivity by inhibiting visceral pain regulated by the PI3K/AKT pathway.Full summaryAcupressure electrical stimulation may reduce the postoperative CRBD incidence and reduce the CRBD severity in TURP patients by inhibiting visceral pain regulated by the PI3K/AKT pathway. |
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