The Study On The Leukocytes Mechanism Of Elevated Pain Threshold In Patients With Obstructive Jaundice

Obstructive jaundice is a common disease and often requires surgery treatment.Most previous studies focused on the sensitivity of inhaled anesthetics, andhemodynamic stability and muscle relaxants with liver and kidney metabolism. Whileobstructive jaundice caused by increased pain threshold did not give enough attention,so more complications and higher mortality caused by jaundice perioperative highincidence of delayed recovery has not been resolved until now. Therefore, wemeasured the basis of clinical surgery pain threshold in the present study and detectedthe leukocytes from normal people and patients with obstructive jaundice. Further, themechanism by which jaundice caused increased pain threshold.The present study recruited patients with ASAI-II obstructive jaundice (n=18,TBL>20μM) and non-obstructive jaundice patients (n=16, TBL<20μM). We usedEP601C surveying instrument to measure pain threshold. PCA devices was connectedinto patients postoperation and morphine consumption was monitored. Peripheralblood was extracted before operation and plasma β-endorphin levels was detected byELISA assay. We also examined μ-opioid receptor level and the secreted β-endorphinfrom leukocytes. The μ-opioid receptor and β-endorphin levels were also measured byFlow Cytometry and ELISA from leukocytes afer treated with bilirubin. Therelationship between pain threshold change and peripheral leukocytes with differentlevel ofΜ-opioid receptor was also investigated. Finally, a rat model of obstructivejaundice was constructed. The rats were given cyclosporine and ICAM-1antibodyand the pain threshold change was detected. The results will further demostrated themechanism by which leukocytes affecting pain threshold increasing.The main results are showed here:1. The jaundice patient’s pain threshold according to jaundice index wassignificantly higher than in patients with normal bilirubin levels. We also observedmorphine consumption in post-operation patients after48h. The results indicated thatjaundice patient’s morphine consumption was significantly less than the non-jaundicepatients and morphine consumption and bilirubin levels also showed some correlation.2. Jaundice patient’s plasma β-endorphin levels were much higher than that incontrol patients. Used of QRT-PCR, β-endorphin precursor POMC levels weremeasured in purified leukocytes in the two groups of patients. Jaundice POMC levels in peripheral blood leukocytes were much higher than that in non-jaundice patients,which further suggests the pain threshold in patients with jaundice elevated may dueto some changes in leukocyte. PCR results suggested that leukocyte surface μ opioidreceptor levels in patients with high jaundice were higher than control patients. Theresults indicate there were more opioids in jaundice leukocytes.3. In an animal model of obstructive jaundice, after BDL for7days, cyclosporinewas administrated to rats and pain threshold was measured. The results showed thatcyclosporine could reversed the incresed pain threshold caused by obstructivejaundice. In another animal experiment, we grouped the animals into two high andlow doses of ICAM-1antibody (0.5mg/kg,1mg/kg) and the mechanical pain levelswere measured. We found that the two doses of ICAM-1both reversed the basiselevated pain threshold induced by jaundice. This data confirmed our hypothsis thatpain threshold elevation correlated with the relevance of leukocyte adhesion. We alsoinvestigated the relationship between increased pain threshold and leukocytes throughinhibition of leukocyte differentiation. Taken together, jaundice induces basic painthreshold in the patients, which may be caused by enhanced adhesion of leukocytes.Conclusion:1. The jaundice patient’s pain threshold according to jaundice index was significantlyhigher than in patients with normal bilirubin levels and jaundice patient’s morphineconsumption was significantly less than the non-jaundice patients.2. μ opioid receptor levels in patients with high jaundice were higher than controlpatients. The high bilirubin will cause high level of μ opioid receptor levels.3. Inhibiting activation and adheration of leukocytes will decrease pain threshold,indicating the role of peripheral leukocyte in incresed threshold.