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Pain is a complex physiological and psychological activity, involving at least three dimensions, including pain sensation, pain emotion, and pain cognition. Acupuncture can clearly relieve the pain sensation of patients and improve pain emotion and pain cognition induced by pain; acupuncture participates in the multi-dimensional regulation of pain through brain regions of the limbic system such as anterior cingulate cortex (ACC), amygdala (AMY), and hippocampus. By analyzing relevant literature, it has been found that the regulation of acupuncture on pain emotion is mainly related to the activation of pertinent opioid receptors in the ACC, the decrease of the expression of extracellular signal-regulated kinase (ERK), and the promotion of the expression of glutamic acid (Glu) A1, metabotropic glutamate receptor-1 (mGluR1), and γ-aminobutyric acid aminobutyric acid (GABA) B2 protein in the AMY. The regulation of acupuncture on pain cognition is mainly related to the elevation of the expression of protein kinase A (PKA) and phospho-p38 mitogen-activated protein kinase (phospho-p38 MAPK) and the inhibition of cyclic adenosine monophosphate (cAMP)/PKA/cAMP response element-binding protein (CREB) signaling pathway in the ACC.
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BACKGROUND: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. METHODS: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG (10 μg, 30 μg, 100 μg, and 300 μg) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG 300 μg in order to assess the involvement of SOG with an opioid receptor. The protein levels of the δ-opioid receptor, κ-opioid receptor, and μ-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. RESULTS: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of 300 μg at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was 191.3 μg (95% confidence interval, 102.3–357.8). The antinociceptive effects of SOG (300 μg) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. CONCLUSIONS: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.
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Animals , Humans , Male , Rats , Analgesia , Blotting, Western , Catheters , Dimethyl Sulfoxide , Hyperalgesia , Models, Animal , Naloxone , Nociceptive Pain , Pain, Postoperative , Rats, Sprague-Dawley , Receptors, Opioid , Spinal CordABSTRACT
Objective To evaluate the role of different opioid receptors in morphine postconditioning-induced reduction of ischemia-reperfusion (Ⅰ/R) injury in isolated rat hearts.Methods Healthy adult male Sprague-Dawley rats,aged 7-8 weeks,weighing 250-300 g,were anesthetized with chloral hydrate.The hearts were removed and retrogradely perfused with oxygenated K-H solution in a Langendorff apparatus.Forty-eight Langendorff-perfused rat hearts were divided into 4 groups (n=12 each) by a random number table method:Ⅰ/R group,morphine postconditioning group (M group),δ receptor antagonist naltrexone plus morphine postconditioning group (N+M group) and κ receptor antagonist nor-binaltorphimine plus morphine postconditioning group (B+M group).Hearts were subjected to 4 cycles of perfusion with K-H solution containing 1 μmol/L morphine for 15 s and then with K-H solution containing no morphine for 15 s in group M.In N+M group and B+M group,hearts were perfused with 5 μmol/L naltrindole and 5 μmol/L nor-binaltorphimine,respectively,starting from 10 nin of equilibration until 5 min of reperfusion,and morphine postconditioning was similar to those previously described in group M.Heart rate and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were recorded at 20 min of equilibration and 30 and 60 nin of reperfusion.Corona~ effluent was collected at 20 min of equilibration and 60 min of reperfusion for measurement of the activity of creatine kinase by colorimetric assay.Eight hearts were obtained at 60 min of reperfusion for determination of myocardial infarct size.Four hearts were obtained at 60 min of reperfusion for detection of the expression of microtubule-associated protein 1 light chain 3 Ⅰ (LC3 Ⅰ) and LC3 Ⅱ by Western blot.LC3 Ⅱ/LC3 Ⅰ ratio was calculated.Results Compared with the baseline value at 20 min of equilibration,heart rate and +dp/dt were significantly decreased at 30 and 60 min of reperfusion,and the activity of creatine kinase in coronary effluent was increased at 60 min of reperfusion in four groups (P＜0.05).Compared with group Ⅰ/R,the activity of creatine kinase in coronary effluent,percentage of myocardial infarct size and LC3 Ⅱ/LC3 Ⅰ ratio were significantly decreased in group M (P＜0.05).Compared with group M,the activity of creatine kinase in coronary effluent,percentage of myocardial infarct size and LC3 Ⅱ/LC3 Ⅰ ratio were significantly increased in N+M and B+M groups (P＜0.05).Conclusion δ and κ opioid receptors are involved in morphine postconditioning-induced reduction of Ⅰ/R injury in isolated rat hearts,and the mechanism may be related to inhibiting the level of autophagy.
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Objective To evaluate the role of μ-δ heterodimer in down-regulation of the expression of excitatory amino acid transporter 3 (EAAT3) in hippocampi caused by reinstatement of morphine-induced conditioned place preference (CPP) in rats.Methods Thirty-two healthy clean-grade male Sprague-Dawley rats,weighing 200-240 g,were assigned into 4 groups (n =8 each) using a random number table method:control group (group C),extinction group (group E),reinstatement group (group R) and reinstatement plus interference plasmid group (group RI).The model of morphine-induced CPP was established,and extinction of CPP was gradually induced by stopping administration.A small dose of morphine 5 mg/kg was intraperitoneally injected again to induce CPP reinstatement,and dwell time around the medicine box was recorded.μ-δ heterodimer interference plasmid 5 μl was injected into the lateral cerebral ventricle after successful establishment of CPP model in group RI.The content of glutamate (Glu) in hippocampi was measured using high-performance liquid chromatography.The EAAT3 expression in hippocampal CA1 and CA3 regions was detected using Western blot.Results Compared with group C,no significant change was found in the dwell time around the medicine box or content of Glu in hippocampi (P＞0.05),and the expression of EAAT3 in hippocampal CA1 and CA3 regions was significantly up-regulated in group E,and the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased (P＜0.05),and no significant change was found in the expression of EAAT3 in hippocampal CA1 and CA3 regions in group R (P＞0.05).Compared with group E,the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased,and the expression of EAAT3 in hippocampal CA1 and CA3 regions was down-regulated in group R (P＜0.05).Compared with group R,the dwell time around the medicine box was significantly shortened,the content of Glu in hippocampi was decreased,and the expression of EAAT3 in hippocampal CA 1 and CA3 regions was upregulated in group RI (P＜0.05).Conclusion μ-δ heterodimer is involved in down-regulation of EAAT3 expression in the hippocampus caused by reinstatement of morphine-induced CPP in rats.
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Objective To evaluate the role of μ opioid receptor in morphine preconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats with chronic heart failure.Methods Adult male Sprague-Dawley rats,weighing 170-230 g,in which chronic heart failure was induced by injecting doxorubicin via the tail vein,were studied.The rats were sacrificed and their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Forty isolated rat hearts with I/R injury were randomly divided into 4 groups (n=10 each):group I/R,morphine preconditioning group (group MP),μ opioid receptor antagonist CTOP plus morphine preconditioning group (group CTOP+MP) and CTOP group.Myocardial I/R was induced by occlusion of the left coronary artery for 30 min followed by 120 min of reperfusion.In group MP,the hearts were perfused with K-H solution for 15 min,with K-H solution containing 1 μmol/L morphine for 5 min and with K-H solution for 5 min,3 cycles in total,and then the model of myocardial I/R was established.The hearts were perfused with K-H solution containing 1 μmol/L CTOP starting from 10 min before morphine preconditioning until 5 min of ischemia in group CTOP + MP.The hearts were perfused with K-H solution containing 1 μmol/L CTOP starting from 40 min before ischemia until 5 min of ischemia in group CTOP.The coronary effluent was collected at 15 min of equilibration (baseline) and 5 and 10 min of reperfusion to detect the activity of lactate dehydrogenase (LDH).Myocardial infarct size (IS) and the area at risk (AAR) were measured by 2,3,5-triphenyl-tetrazolium staining,and IS/AAR percentage was calculated.The expression of Bcl-2 and Bax mRNA was determined using uantitative real-time polymerase chain reaction,and the ratio of Bcl-2/Bax was calculated.Results Compared with group I/R,the IS and IS/AAR percentage were significantly decreased,the activity of LDH in coronary effluent was decreased,the expression of Bax mRNA was downregulated,the expression of Bcl-2 mRNA was up-regulated,and the Bcl-2/Bax ratio was increased in group MP (P＜0.05),and no significant change was found in the IS or IS/AAR percentage in CTOP and CTOP+ MP groups (P＞0.05).Compared with group MP,the IS and IS/AAR percentage were significantly increased,the activity of LDH in coronary effluent was increased,the expression of Bax mRNA was up-regulated,the expression of Bcl-2 mRNA was down-regulated,and the Bcl-2/Bax ratio was decreased in group CTOP+MP (P＜0.05).Conclusion The mechanism by which morphine preconditioning reduces myocardial I/R injury may be related to activating μ opioid receptors and thus maintaining the balance between Bcl2 and Bax gene expression in the rats with chronic heart failure.
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Objective To evaluate the effect of oxycodone pretreatment on oxygen-glucose deprivation and restoration (OGD/R)-induced injury to small intestinal epithelial cells of rats and the role of different opioid receptors.Methods IEC-6 cells were divided into 5 groups (n=15 each) using a random number table:control group (group C),group OGD/R,oxycodone group (group O),μ opioid receptor antagonist CTOP plus oxycodone group (group CTOP+O) and κ opioid receptor antagonist BNI plus oxycodone group (group BNI+O).Cells were cultured for 8 h in normal culture atmosphere in group C.Cells were subjected to OGD for 4 h followed by restoration of oxygen-glucose supply in normal culture medium for 4 h in OGD/R,O,CTOP+O and BNI+O groups.Oxycodone at a final concentration of 1 μg/ml was added at 5 min before OGD/R in O,CTOP+O and BNI+O groups.CTOP and BNI at a final concentration of 5 μmol/L were added at 10 min before OGD/R in group CTOP+O and group BNI+O,respectively.Five holes in each group were selected at 8 h of OGD/R for determination of the cell viability (by MTT assay),lactic dehydrogenase (LDH) release rate (by colorimetry) and levels of tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β) and high-mobility group box 1 protein (HMGB1) in supernatant (by enzyme-linked immunosorbent assay).Results Compared with group C,the cell viability was significantly decreased,and the LDH release rate and levels of TNF-α,IL-1β and HMGB1 were increased in OGD/R,O,CTOP+Oand BNI+ O groups (P＜ 0.05).Compared with group OGD/R,the cell viability was significantly increased,and the LDH release rate and levels of TNF-o,IL-1β and HMGB1 were decreased in group O (P＜0.05).Compared with group O,the cell viability was significantly decreased,and the LDH release rate and levels of TNF-α,IL-1β and HMGB1 were increased in CTOP+O and BNI+O groups (P＜0.05).Conclusion Oxycodone pretreatment can mitigate OGD/R-induced injury to small intestinal epithelial cells of rats and the mechanism is related to activating μ and κ opioid receptors.
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Objective To investigate the effect of U50488H on postoperative cognitive dysfunction induced by cardiopulmonary bypass (CPB) in rats.Methods Forty-eight adult male Sprague-Dawley rats,weighing 400-450 g,were divided into 3 groups (n=16 each) using a random number table:sham operation group (group S),CPB group and CPB plus U50488H group (group U).CPB was performed for 60 min in group CPB.U50488H 1.5 mg/kg was injected into the left lateral cerebral ventricle at 30 min prior to CPB,and then CPB was performed for 60 min in group U.Eight rats in each group were selected at 1 day after CPB,and venous blood samples were collected for determination of serum S100β protein,interleukin-lbeta (IL-1 β) and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay).Then the rats were sacrificed and right hippocampi were removed for examination of the pathological changes after haematoxylin and eosin staining.Eight rats were selected from each group at 7 days after CPB for assessment of cognitive function.Results Compared with group S,the concentrations of serum S100β protein,IL-1β and TNF-α were significantly increased in group CPB,and the escape latency was prolonged,the number of crossing original platform was reduced,and the swimming distance in target quadrant and time of staying at target quadrant were shortened in CPB and U groups (P＜0.05).Cormpared with group CPB,the concentrations of serum S100β protein,IL-1β and TNF-α were significantly decreased,the escape latency was shortened,the number of crossing original platform was increased,the swimming distance in target quadrant and time of staying at target quadrant were prolonged (P＜0.05),and the pathological changes of hippocampal tissues were significantly attenuated in group U.Conclusion U50488H can mitigate the postoperative cognitive dysfunction induced by CPB in rats.
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The delta-opioid receptor (DOR),which is a classic analgesic drug widely existed in the central system and peripheral system,is a kind of inhibitory G-protein coupled receptor with seven transmembrane regions.In addition to pain modulation,the opioid receptors are involved in various physiological and pathological activities through gene or cytokines.This review addresses the influence and possible mechanisms of the delta-opioid receptor in ischemic brain injury,analgesia,anti-anxiety and depression,learning and memory,and Parkinson's disease.
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Objective To evaluate the role of δ-opioid receptors in hydromorphone postcondition-ing-induced maintenance of electrophysiological stability during ischemia-reperfusion(I∕R)in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg∕kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Thirty-two isolated hearts were divided into 4 groups after successful preparation of Langendorff perfusion model(n=8 each)using a random number ta-ble: control group(group C), group I∕R, hydromorphone postconditioning group(group HP)and hydro-morphone plus δ-opioid receptor antagonist naltridole postconditioning group(group HNP). In HP and HNP groups, the hearts were perfused for 10 min with K-H solution containing 41 ng∕ml hydromorphone and 41 ng∕ml hydromorphone plus 5 μmol∕L naltridole, respectively, and then with K-H solution for 50 min. At 20 min of stabilization(T0)and 10, 25 and 60 min of reperfusion(T1-2), heart rate(HR), monophasic action potential(MAP)duration at 90% repolarization(MAPD90)of the two layers(endocar-dium, epicardium)of the anterior left ventricular wall were recorded. Transmural dispersion of repolariza-tion(TDR)was calculated. The development of arrhythmia, time for restoration of spontaneous heart beat and duration of arrhythmia were recorded during the period of reperfusion. Results Compared with group C, MAPD90of endocardium at T1-2and MAPD90of epicardium at T1were significantly prolonged in I∕R and HP groups, HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3in group HNP, TDR was significantly enlarged at T1in group I∕R and at T2in group HNP, and TDR was decreased at T3in group HP(P<005). Compared with group I∕R, no significant change was found in arrhythmia score(P>005), the time for restoration of spontaneous heart beat was significantly shortened, and TDR was decreased at T1in HP and HNP groups, duration of arrhythmia was significantly shortened, and MAPD90of endocardium was shortened at T1in group HP, and HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was decreased at T2-3in group HNP(P<005). Compared with group HP, no significant change was found in time for restoration of spon-taneous heart beat, duration of arrhythmia or arrhythmia score(P>005), HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was increased at T3in group HNP(P<005). Conclusion The mechanism underlying hydromorphone postconditioning-induced maintenance of electrophysiological stability during I∕R is related to activating δ-opioid receptors in isolated rat hearts.
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Objective To evaluate the effect of oxycodone on migration of human colon cancer cells and the role of μ and κ receptors.Methods The human colon cancer HCT116 cells at the logarithmic growth phase were seeded in 24-well or in 6-well plates at a density of 1 × 106 cells/mnl (0.5 ml/well or 2 ml/well,144 wells in total).The cells were divided into 6 groups (n=24 each) using a random number table:control group (group C),1,5 and 10 μmol/L oxycodone groups (group O1,group O2 and group O3),oxycodone plus μ receptor antagonist CTOP group (group O2+CTOP) and oxycodone plus κ receptor antagonist nor-binaltorphimine group (group O2+BNI).The cells were incubated for 24 h with oxycodone 1,5 and 10 μmol/L in O1,O2 and O3 groups,respectively.The cells were incubated for 24 h with 5 μmol/L oxycodone plus 20 μmol/L CTOP and 5 μmol/L oxycodone plus nor-binahorphimin 20 μmol/L in O2+CTOP and O2+BNI groups,respectively.The invaded and migrated cells were counted,and the levels of Ras homolog gene family member A (RhoA),Rho-associated protein kinase 1 (ROCK1),matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected.Results Compared with group C,the number of invaded and migrated cells was gradually decreased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were gradually decreased in O1,O2 and O3 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+BNI (P＞0.05).Compared with group O2,the number of invaded and migrated cells was significantly increased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were increased in group O2 + BNI (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+CTOP (P＞0.05).Conclusion Oxyc odone can inhibit the migration of human colon cancer cells,and the mechanism is totally related to inhibition of RhoA/ROCKl signaling pathway activation after activating κ receptors,but not related to μ receptors.
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Objective To evaluate the efficacy of nalmefene in preventing sufentanil-induced cough during induction of general anesthesia.Methods One hundred American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes,aged 21-62 yr,weighing 45-82 kg,undergoing elective laparoscopic cholecystectomy under general anesthesia,were divided into 2 groups (n =50 each) using a random number table:nalmefene group (group N) and control group (group C).Nalmefene 0.25 μg/kg was injected intravenously at 2 min before anesthesia induction in group N,and the equal volume of normal saline was given instead in group C.Anesthesia was induced with target-controlled infusion of propofol,and sufentanil 0.5 μg/kg was injected over 5 s when bispectral index value reached 55.The number of patients who developed cough within 2 min after sufentanil injection and severity of cough were observed.Other iv anesthetics were given for induction after the end of observation.Results The incidence of sufentanil-induced cough was 8％ in group N and 48％ in group C.Compared with group C,the incidence and severity of cough were significantly decreased in group N (P＜0.05).Conclusion Nalmefene 0.25 μg/kg injected at 2 min before induction of anesthesia can effectively decrease the development of sufentanil-induced cough during induction of general anesthesia.
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Objective To evaluate the role of spinal κ-opioid receptors in remifentanil-induced postoperative central sensitization in a rat model of incisional pain by in vivo electrophysiology.Methods Sixty adult male Sprague-Dawley rats in which intrathecal catheters were successfully implanted,weighing 230-270 g,were divided into 5 groups (n=12 each) using a random number table:control group (group C),incisional pain group (group I),remifentanil group (group R),remifentanil plus incisional pain group (group R+I),and κ-opioid receptor agonist U50488H group (group U).A 1 cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the right hind paw in isofiurane-anesthetized rats to establish the model of incisional pain.Remifentanil was intravenously infused for 1 h at a rate of 10 μg · kg 1 · min-1 in group R.In group R+I,remifentanil was intravenously infused for 1 h at a rate of 10 μg · kg-1 · min 1,and the model of incisional pain was established at the same time.In group U,U50488H 10 μg/10μl was injected intrathecally,30 min later remifentanil was intravenously infused for 1 h at a rate of 10 μg · kg-1 · min-1,and the model of incisional pain was established.Six rats in each group were randomly selected,the mechanical pain threshold (MPT) was measured in bilateral hind paws before implanting intrathecal catheter (T0),before operation (T1),and at 1 h,4 h and 1,2 and 3 clays after operation (T2-6).Six rats in each group were randomly selected to record the C fiber-evoked filed potentials in the spinal dorsal horn from 60 min before administration or operation to 180 min after administration or operation,the long-term potentiation (LTP) induced was also recorded,and the area under the curve (AUC) of C-fiber-evoked field potentials was calculated.Results No LTP was recorded in C,I and U groups,and the LTP was recorded in R and R+I groups.Compared with group C,the MPT in bilateral hind paws at T5,6 was significantly decreased in group R,the MPT in ipsilateral hind paws at T2 6 was decreased in group I,the MPT in ipsilateral hind paws at T2-6 and in contralateral hind paws at T5,6 was decreased in group R+I,the MPT in ipsilateral hind paws at T2-4 was decreased in group U,and the AUC of C-fiber-evoked field potentials was increased in R and R+I groups (P＜0.05).Compared with group Ⅰ,the MPT in ipsilateral hind paws at T4-6 and in contralateral hind paws at T5,6 was significantly decreased,and the AUC of C-fiber-evoked field potentials was increased in group R+I (P＜0.05).Compared with group R+ I,the MPT in ipsilateral hind paws at T2-6 and in contralateral hind paws at T5,6 was significantly increased,and the AUC of C-fiber-evoked field potentials was decreased in group U (P＜0.05).Conclusion The results of in vivo electrophysiology confirm that inhibition of spinal κ-opioid receptor function mav be involved in the mechanism by which remifentanil induces postoperative central sensitization in a rat model of incisional pain.
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Objective To evaluate the effect of the opioid switch from morphine to sufentanil on the expression of μ-opioid receptors in the midbrain periaqueductal gray (PAG) of rats.Methods Forty healthy male Wistar rats,aged 8 weeks,weighing 250-290 g,were randomly assigned into 5 groups (n=8 each) using a random number table:control group (group C),7 day sufentanil group (group S),7 day morphine group (group M),14 day morphine group (group MM),and 14 day alternate administration of morphine and sufentanil group (group MS).Normal saline 2 ml/kg,sufentanil 0.01 mg/kg and morphine 10 mg/kg were injected subcutaneously in the cervical region twice a day for 7 consecutive days in C,S and M groups,respectively.In group MM,morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 14 consecutive days.In group MS,morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 7 consecutive days (1st-7th days),and sufentanil 0.01 mg/kg was then injected subcutaneously in the cervical region twice a day for 7 consecutive days (8th-14th days).The tail flick latency (TFL) to a thermal nociceptive stimulus was measured at 15 and 30 min after the initial administration every day.After the last administration,the rats were sacrificed,and the midbrain PAG was isolated for determination of the expression of the μ-opioid receptor and μ-opioid receptor mRNA using Western blot and real-time reverse transcriptase polymerase chain reaction,respectively.Results Compared with group C,the TFL was significantly prolonged on 1st-6th days after the beginning of administration in M,MM and MS groups,the TFL was significantly prolonged on 1st-7th days after the beginning of administration in group S,and the expression of the μ-opioid receptor and μ-opioid receptor mRNA in the midbrain PAG was significantly down-regulated in M,MM and MS groups (P＜0.05).Compared with group MM,the TFL was significantly prolonged on 8th-14th days after the beginning of administration,and the expression of the μ-opioid receptor and μ-opioid receptor mRNA in the midbrain PAG was significantly up-regulated in group MS (P＜0.05).Conclusion The mechanism by which the opioid switch from morphine to sufentanil reduces morphine tolerance is related to enhanced activity of μ-opioid receptors in the midbrain PAG of rats.
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Cancer pain is the most important factor affecting the cancer patients' quality of life, and the approach to relieve and control cancer pain is becoming the focus. Pain mechanism research can offer solutions to pain treatment, such as blocking the happening and conduction of analgesia. The earliest μ, κ, σopioid receptors were found in the research of morphine and opioid peptides, especially μ receptor's leading role in pain treatment. Currently, μ opioid agonist is basically used in clinical pain treatment. Morphine, the third level drug, is still the classic pain therapy drugs. Novel drugs such as fentanyl transdermal and controlled-release oxycodone provide new ideas for the pain ease. Opioid combined with non-opioid drugs, the change of opioid drugs delivery way and joint application of controlled release drug and relievers, have dramatically reduced opioid drugs' side effects.
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ABSTRACT Purposes: To evaluate the effects of nalbuphine 1% on the expression of metalloproteinase 1 (MMP-1), metalloproteinase 9 (MMP-9), and opioid growth factor (OGF) in rabbit corneas after lamellar keratectomy. Methods: The rabbits were assigned to two groups: group nalbuphine (GN, n=30), which received 30 µL of nalbuphine 1% in 4 daily applications at regular intervals until corneal epithelialization, and group control (GC, n=30), which received physiological saline solution under the same conditions adopted in GN. The corneas were collected for immunohistochemistry on days 1, 3, 5, 7, and 9 after lamellar keratectomy, and the expressions of MMP-1, MMP-9, and OGF were analyzed. Results: The expressions of MMP-1 and MMP-9 increased until day 5 of the evaluation, with no differences observed between GN and GC (p>0.05). On days 7 and 9, significant reductions were observed in the expression of MMP-1 (p<0.01), with no differences observed between GN and GC (p>0.05). The expression of OGF was constant in all periods (p>0.05), restricted to the corneal epithelium, and there was no difference between the groups (p>0.05). Conclusions: The study results showed that nalbuphine 1% did not alter the expression patterns of MMP-1, MMP-9, and OGF in rabbit corneas after lamellar keratectomy. .
RESUMO Objetivos: Avaliar os efeitos da nalbufina 1% sobre a expressão da metaloproteinase 1 (MMP-1), da metaloproteinase 9 (MMP-9) e do fator de crescimento opióide (OGF), em córneas de coelhos submetidas à ceratectomia lamelar. Métodos: Constituíram-se dois grupos: grupo nalbufina (GN, n=30), que recebeu 30 µL de nalbufina 1% em 4 aplicações diárias, a intervalos regulares, até a epitelização corneal; controle (GC, n=30), que recebeu solução salina nas mesmas condições adotadas no GN. As córneas foram colhidas para imuno-histoquímica decorridos 1, 3, 5, 7 e 9 dias das ceratectomias lamelares, visando a se avaliarem as MMP-1, MMP-9 e OGF. Resultados: A expressão das MMP-1 e de MMP-9 se elevou até o quinto dia de avaliação, sem diferença entre GN e GC (p>0,05). Nos dias 7 e 9, observou-se redução significativa na expressão das enzimas (p<0,01), sendo que diferenças não foram observadas entre os grupos (p>0,05). O OGF exibiu imunomarcação constante em todos os períodos (p>0,05), restrita ao epitélio corneal. Não foram encontradas diferenças entre os grupos (p>0,05). Conclusões: Com base dos resultados obtidos, há como admitir que a nalbufina 1% não alterou o padrão de expressão da MMP-1, da MMP-9 e do OGF em córneas de coelhos submetidas à ceratectomia lamelar. .
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Animals , Male , Rabbits , Analgesics, Opioid/pharmacology , Epithelium, Corneal/drug effects , Matrix Metalloproteinase 1/drug effects , Matrix Metalloproteinase 9/drug effects , Nalbuphine/pharmacology , Receptors, Opioid/drug effects , Analgesics, Opioid/administration & dosage , Corneal Stroma/metabolism , Corneal Stroma/pathology , Epithelium, Corneal/metabolism , Immunohistochemistry , Models, Animal , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Nalbuphine/administration & dosage , Receptors, Opioid/metabolism , Refractive Surgical Procedures/methodsABSTRACT
Objective To compare the inhibitory effects of Butorphanol and Dezocine on Etomidate-induced myoclo?nus. Methods A total of 150 patients with ASA physical statusⅠorⅡ, aged 40-65 yr, with body mass index (BMI) of 20-25 kg/m2, scheduled for elective operations under general anesthesia, were included in this study. Patients were randomly al?located into three groups (A, B and C) with 50 patients in each group. Group A was given intravenous Butorphanol 15 μg/kg for 30 s, group B was given Dezocine 0.1 mg/kg and group C was given equal volume of saline. After 2 min, etomidate 0.3 mg/kg was administrated to three groups. The occurrence and severity of myoclonus were recorded for 2 min after administration of Etomidate. The mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SpO2) and Bispectral index (BIS) were recorded at the time points before induction (T0), 2 min after the experimental drug treatment (T1), and 2 min after Etomi?date treatment (T2). At the same time, the concentration of serum potassium was determined at T0 and 5 min after endotrache?al intubation (T3) respectively. Results The positive incidences of myoclonus were 12%in group A, 22%in group B and 74%in group C, respectively. Compared with group C, the positive incidence rates of myoclonus and myoclonus scales were significantly lower in group A and group B (P0.05). Compared with T0, there was no significant difference in the potassium concentration between patients without myoclonus (grade 0) and patients with myoclonus (grade 1 and grade 2) at T3 (P>0.05). There was a significant increase in potassium concentration in patients with grade 3 (P0.05). Conclusion Pre-treatment of Butorphanol (15μg/kg) or Dezocine (0.1 mg/kg) can reduce the Etomidate-induced myoclonus. At the same time, both therapies show no different effects on cir?culation and respiration system.
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Background:Ulcerative colitis(UC)is a chronic and nonspecific intestinal inflammatory disease and its pathogenic mechanism has not yet been clarified. Intestinal mucosal immune function disorder may play a key role in the pathogenesis of UC. Aims:To investigate the effects of Wumeiwan on expressions of δ-opioid receptor(DOR),β-arrestin1 and Bcl-2 in rats with colitis. Methods:Fifty-six Sprague-Dawley rats were randomly divided into model group,Wumeiwan group, mesalazine group and blank group. Rats in model group,Wumeiwan group and mesalazine group were administered intrarectally with 5% TNBS and 50% ethanol to induce experimental colitis. After colitis models were established,rats in Wumeiwan group and mesalazine group were administered intragastrically with Wumeiwan and mesalazine suspension, respectively,and rats in model group and blank group were given intragastrically with 0. 9% NaCl solution,all for 15 days. On day 16,all the rats were sacrificed and colon samples were obtained. Protein and mRNA expressions of DOR,β-arrestin1 and Bcl-2 in colonic tissue were determined by immunohistochemistry and real-time PCR,respectively. Results:The inflammatory injury in colonic tissue of rats with experimental colitis was significantly attenuated when treated with Wumeiwan,Protein and mRNA expressions of DOR,β-arrestin1 and Bcl-2 in colonic tissue of model group were significantly higher than those of blank group(P 0. 05). Conclusions:DOR-β-arrestin1-Bcl-2 signal transduction pathway may play a central role in the pathogenesis of UC. Intervening this signaling pathway may be one of the mechanisms of attenuating UC by Wumeiwan.
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Objective To evaluate the relationship between delta opioid receptors (DORs) and activity of glycogen synthase kinase-3β (GSK-3β) in the spinal cord during hyperalgesia induced by remifentanil in a rat model of incisional pain (IP).Methods Twenty-four male Sprague-Dawley rats,aged 240-260 g,weighing 2-3 months,were randomly divided into 3 groups (n =8 each) using a random number table:control group (group C),remifentanil+IP group (group R+I) and DOR antagonist naltrindole group (group N).A 1-cm longitudinal incision was made in the plantar surface of the left hindpaw in anesthetized rats.In group C,the equal volume of normal saline was injected intraperitoneally,and normal saline was then infused for 60 min at the same rate.In group R+I,the equal volume of normal saline was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.In group N,naltrindole 0.1 mg/kg was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.At 24 h before infusion of normal saline or remifentanil and 2,6,24 and 48 h after iv administration (T0-4),the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold,the lumbar segment (L4-6) of the spinal cord was removed for determination of the expression of GSK-3β,phosphor-GSK-3β (pGSK-3β) (by Western blot) and GSK-3β mRNA (realtime PCR).The ratio of pGSK-3β /GSK-3β was calculated.Results Compared with group C,the MWT was significantly decreased,and the TWL was shortened at T1 4,the expression of GSK-3β,pGSK-3β and GSK-3β mRNA was up-regulated,and pGSK-3β/GSK-3β ratio was decreased in R + I and N groups.Compared with group R + I,thc MWT was significantly incrcased,and the TWL was prolonged at T1-4,the expression of GSK-3β,pGSK-3β and GSK-3β rmRNA was down-regulated,and pGSK-3β/GSK-3β ratio was increased in group N.Conclusion Activation of DOR is involved in enhancement of activity of GSK-3β in the spinal cord during hyperalgesia induced by remifentanil in a rat model of IP.
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Objective To evaluate the effect of remifentanil preconditioning ( RP ) on intestinal is?chemia?reperfusion ( I∕R) injury in rats and its relationship with opioid receptors. Methods Seventy?two Sprague?Dawley rats, aged 6-7 weeks, weighing 250-280 g, were randomly divided to 9 groups ( n=8 each): sham operation group (S), intestinal I∕R group (group I∕R), RP group, different opioid receptor antagonists groups (N, BNI and CTOP groups), and opioid receptor antagonists + RP groups (N+RP, BNI+RP and CTOP+RP groups) . Intestinal I∕R was produced by clamping the superior mesenteric artery for 1 h followed by 2 h reperfusion in all the groups except group S. RP was induced by 3 cycles of 5 min infusion of remifentanil 0?2 μg·kg-1 ·min -1 followed by 5 min infusion of normal saline before ischemia. Naltrindole (δ?receptor antagonist, 5 mg∕kg) , nor?binaltorphimine (κ?receptor antagonist, 5 mg∕kg) and CTOP (μ?receptor antagonist, 1 mg∕kg) were administered before RP. At 2 h of reperfusion, blood sam?ples were collected from the cardiac apex for determination of serum diamine oxidase ( DAO) activity. Intes? tinal tissues were then removed for microscopic examination. Intestinal damage was assessed and scored ac?cording to Chiu. Apoptosis in intestinal mucosal epithelial cells was detected using TUNEL assay, and ap?optosis index was calculated. The expression of activated caspase?3 in intestinal mucosal epithelial cells was measured by Western blot. Results Compared with group S, the serum DAO activity, Chiu′s score, and apoptosis index were significantly increased, and the expression of activated caspase?3 was up?regulated in I∕R and RP groups ( P0?05). Compared with group RP, the serum DAO activity, Chiu′s score, and apoptosis index were significantly increased, and the expression of activa?ted caspase?3 was up?regulated in N+RP and CTOP+RP groups ( P0?05) . Conclusion RP can mitigate in?testinal I∕R injury in rats, and the mechanism is related to the anti?apoptotic effect mediated by activation ofδ?and μ?opioid receptors, but not κ?opioid receptors.
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Objective To evaluate the effect of oxycodone preconditioning on liver injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of different opioid receptors.Methods Fiftyfour adult male Sprague-Dawley rats, weighing 200-300 g, were randomly divided into 9 groups (n =6 each) using a random number table: sham operation group (group S), group I/R, oxycodone preconditioning group (group OP) , μ receptor antagonist CTOP group (group CTOP) , δ receptor antagonist naltrindole group (group NTD), κ receptor antagonist nor-binaltorphimne group (group BNI), CTOP + oxycodo ne preconditioning group (group CTOP+OP) , naltrindole + oxycodone preconditioning group (group NTD+ OP) , and nor-binaltorphimne + oxycodone preconditioning group (BNI+OP).The model of intestinal I/R was established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized rats.The superior mesenteric artery was only exposed, but not occluded in group S.In OP,COTP+OP, NTD+OP and BNI+OP groups, oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia.COTP 1 mg/kg and naltrindole 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+OP and NTD+OP groups, respectively.Nor-binaltorphimne 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+OP.In CTOP and NTD groups, the corresponding doses of CTOP and naltrindole were injected intravenously at 10 min prior to ischemia.In group BNI, the corresponding dose of nor-binaltorphimne was injected intravenously at 15 min prior to ischemia.The rats were sacrificed at 2 h of reperfusion, and left hepatic lobes were removed for microscopic examination and for detection of apoptosis in liver cells (using TUNEL).The apoptosis index (AI) was calculated.Results Compared with group S, the AI was significantly increased in the other groups (P＜0.05).Compared with group I/R, the AI was significantly decreased (P＜0.05) , and the pathological changes of livers were reduced in OP, COTP+OP, NTD+OP and BNI+OP groups, and no significant change was found in AI and pathological changes of livers in CTOP, NTD and BNI groups (P＞0.05).Compared with group OP, the AI was significantly increased (P＜0.05), and the pathological changes of livers were aggravated in COTP+ OP, NTD+OP and BNI+OP groups.There was no significant difference in AI and pathological changes of livers among groups COTP+OP, NTD+OP and BNI+OP (P＞0.05).Conclusion Oxycodone preconditioning can mitigate liver injury induced by intestinal I/R in rats, and μ, δ and κ receptors mediate the role with comparable effects.