| BACKGROUNDOpioid-induced hyperalgesia(OIH)is a sensory abnormality characterized by opioid-induced hyperalgesia(OIH)in opioid-induced patients with opioid-induced hyperalgesia(OIH).Remifentanil is a kind of micron-receptor agonist,the effect is rapid,the half-life is short and constant,there is no accumulation of repeated drugs,because of these good pharmacokinetic characteristics,remifentanil widely used in clinical anesthesia in recent years.However,clinical studies have shown that remifentanil is prone to pain and hyperalgesia after drug withdrawal,and more analgesics are needed,resulting in more frequent hyperalgesia than other opioids,making postoperative pain management more difficult and complications significantly increased.How to treat and prevent remifentanil induced hyperalgesia and explore its mechanism has become a hot topic in recent years.At present,small doses of opioids are commonly given before surgery to alleviate the pain or hyperalgesia induced by withdrawal of remifentanil.However,the analgesic effect of opioids only covers up the phenomenon of hyperalgesia and does not eliminate the occurrence of hyperalgesia caused by remifentanil in essence.It has been reported that COX in the spinal cord is involved in the occurrence of OIH,and COX antagonists,such as flurbiprofen ester and paracoxib sodium,can effectively inhibit postoperative hyperalgesia induced by remifentanil.Some studies have reported that other drugs,such as ketamine and clonidine,have good clinical effects on inhibiting pain hypersensitivity induced by remifentanil,but there is still controversy.Meta-analysis was conducted on the postoperative use of n.methyl d.aspartic acid(NMDA)receptor antagonists,such as ketamine and magnesium sulfate,in more than 14 central prospective studies.It was reported that NMDA antagonists could not ffectively prevent hyperalgesia induced by remifentanile postoperative.At present,the mechanism of pain hypersensitivity induced by remifentanil,which may be related to the decrease of endogenous opioid concentration.Spinal cord is one of the key parts of opioid tolerance and pain sensitivity.The role of spinal cord and spinal glial cells in the mechanism of remifentanil induced hyperalgesia deserves attention and research.Acupuncture and moxibustion is the traditional medicine of the motherland and has been recognized by many western countries and regions.Electroacupuncture is an effective assistant analgesic method for the determination of the curative effect of chronic pain.Studies shown that the main mechanism of acupuncture analgesia is the release of endogenous opioids,serotonin,adenosine and so on.Because electroacupuncture can produce endogenous opioid and has analgesic effect,there have been researches on the relief of postoperative pain by electroacupuncture in recent years.Previous studies have found that electroacupuncture can reduce morphine tolerance,but the effect of different electroacupuncture output waveforms on pain sensitivity induced by remifentanil anesthesia has rarely been reported.The purpose of this study was to explore the effectiveness of different electroacupuncture output waveforms in alleviating pain hypersensitivity induced by remifentanil and its possible mechanism through clinical study.OBJECTIVEProposed by observing the curative different output waveform of exciting Hegu,Neiguan,Zusanli and Sanyinjiaoand three vaginal intercourse in patients with hereditary disease of grow in quantity of spherical cell line of splenectomy,the influence of fentanyl anesthesia induced hyperalgesia,and detection of peripheral blood in patients with different time points in the βendorphin and prostaglandin E2,serotonin and other inflammatory factor levels and explore its possible mechanism.METHODS80 patients aged 18 to 50 names of quasi spleen resection in patients with hereditary disease of grow in quantity of spherical cell,ASA class or Ⅰ Ⅱ.Patients were divided into 4 groups(n=20)by random number table method: remifentanil group(R group),density wave + remifentanil group(DR group),continuous waveform group + remifentanil group(CR group),intermittent wave + remifentanil group(IR group).The acupuncture group started acupuncture intervention at Hegu,Neiguan,Zusanli and Sanyinjiao point 30 min before anesthesia induction.Electroacupuncture was connected to the pulse therapy instrument and the output waveform was adjusted: density wave 1m A+ 2/15 hz,continuous wave 1m A+15Hz,intermittent wave 1m A+ 0/15 hz.Electroacupuncture stimulation lasted for 1 hour,and the needle was retained until the end of the operation.After operation,the patient’s eye opening time,extubation time and Ramsay sedation score were observed.Pain score(VAS),T4 comfort score(BCS)and mechanical pain threshold(QST)were recorded at 2h(T1),12h(T2),24h(T3)and 48h(T4)after operation.The dosage of sufentanil,recovery analgesia rate,comfort score and pain threshold around incision were recorded within 48 h after operation in the four groups of patients.The total operation time and sufentanil dosage were recorded.The incidence of respiratory depression,hypotension,nausea and vomiting were recorded.The contents of β-EP,PGE2 and 5-HTin blood samples at preoperative(T1),postoperative 2h(T2),24h(T3)and 48h(T4)time points were detected.RESULTS1.There was no significant difference in remifentanil dosage among the four groups(P > 0.05).Compared with group R,the dosage of sufentanil in DR,CR and IR groups decreased,comfort score and pain threshold around incision increased,the incidence of nausea and vomiting decreased,the rate of remedial analgesia in DR group decreased(P < 0.05),and there was no significant difference between CR and IR groups(P > 0.05).Compared with DR group,the dosage of sufentanil in CR and IR groups increased,the rate of remedial analgesia increased,comfort score and pain threshold around incision increased.There was no significant difference in the above indexes between CR group and IR group(P > 0.05).There was no significant difference in the incidence of adverse reactions among DR group,CR group and IR group(P > 0.05).At T1,there was no statistically significant difference in resting VAS between the R group and the CR group,IR group,and the DR group was lower(P<0.05).At T2,the mean values of resting and exercise VAS and postoperative sufentanil dosage in group R were higher than those in CR group,DR group and IR group(P<0.05).Compared with DR group,CR group had higher resting VAS(P<0.05).At T3,the mean dosages of resting VAS and remifentanil in the R group were higher than those in the CR group,DR group and IR group(P<0.05).At the same time,compared with DR group resting VAS,CR group and IR group were higher(P<0.05).Compared with R group,VAS was lower in DR group(P<0.05).At T4,the mean dosages of resting and exercise VAS and postoperative sufentanil in the R group were higher than those in the CR group,DR group and IR group(P<0.05).Compared with the mean dosages of rest and exercise VAS and postoperative sufentanil in DR group,CR group and IR group had higher dosages(P<0.05).QST and BCS in R group were lower than those in CR group,DR group and IR group(P<0.05).QST and BCS in DR group were higher than CR group and IR group(P<0.05).The incidence of nausea and vomiting was low in CR,DR and IR groups.2.The plasma levels of 5-HT at time points of T2 and T3 in DR group were(133.22+40.65 and 52.48+51.15)ng/ml,respectively.Compared with those in R group(167.33+55.84 and 223.28+80.03)ng/ml,CR group(164.14+47.13 and 217.74+76.45))ng/ml,IR group(163.15+47.15 and 215.14+75.65)ng/ml,the levels of 5-HT in DR group were significantly lower than those in R group(163.15+47.15 and 215.14+75.65).No respiratory depression and hypotension occurred in all groups.The plasma levels of β-EP in DR group were(175.94 +44.73)pg/ml and(161.96 +34.11)pg/ml,respectively,as compared with those in R group(133.22 +37.25 and 127.79 +40.54)pg/ml,respectively.The levels of in CR group(136.56+45.81 and 129.85+36.14)and IR group(135.48+44.72 and 128.95+35.84)were significantly higher than those in CR group(P<0.05).The plasma levels of PGE2 in DR group were(41 + 5)pg/ml and(40 + 5)pg/ml at time points of T2 and T3 respectively,which were significantly lower than those in R group(64 + 5 and 62 + 7)pg/ml,CR group(66 + 6 and 62 + 6)pg/ml,IR group(65 + 6 and 61 + 6)pg/ml.CONCLUSIONSThe stimulation of Hegu,Neiguan,Zusanli and Sanyinjiao point by electroacupuncture can inhibit the hyperalgesia induced by remifentanil anesthesia,and the stimulation effect of density wave type output electroacupuncture is the best.The mechanism may be related to the increased production of endogenous β-EP by EAS and the inhibition of the release of inflammatory mediators 5-HTand PGE2. |
