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Objective:To evaluate the effect of intrathecal insulin-like growth factor-1 (IGF-1) on chemotherapy-induced neuropathic pain (NP) in mice.Methods:Forty clean-grade healthy male C57 mice, aged 7-9 weeks, weighing 22-24 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), chemotherapy-induced NP group (group CIPN), low-dose IGF-1 group (group I1) and high-dose IGF-1 group (group I2). In CIPN, I1 and I2 groups, oxaliplatin 5 mg/kg was intraperitoneally injected for 5 consecutive days to establish chemotherapy-induced NP model.Normal saline 0.2 ml was given in group C. After measurement of the pain threshold at 10 days after establishment of the model, IGF-1 0.5 and 1.0 μg were intrathecally injected in group I1 and group I2, respectively.Normal saline 5 μl was intrathecally injected in C and CINP groups.Mechanical withdrawal threshold (MWT) was measured at 3, 5, 8, 10, 11, 13 and 15 days after establishment of the model.After measurement of the pain threshold at 15 days after establishment of the model, the expression of spinal IGF-1, IGF-1receptor (IGF-1R), interleukin (IL)-17A, IL-1β and tumor necrosis factor (TNF)-α was detected, and IGF-1 positive cells were counted using immunofluorescence. Results:Compared with group C, MWT was significantly decreased, the expression of spinal IGF-1 was down-regulated, the count of IGF-1 positive cells was decreased, and expression of IL-17A, IL-1β and TNF-α was up-regulated at 3-25 days after establishment of the model in CINP, I1 and I2 groups ( P<0.05). Compared with group CIPN, MWT was significantly increased at 15 days after establishment of the model in group I1, and MWT was increased, the expression of spinal IGF-1 was up-regulated, the count of IGF-1 positive cells was increased, and expression of IL-17A, IL-1β and TNF-α was down-regulated at 13 and 15 days after establishment of the model in group I2 ( P<0.05). Compared with group I1, the count of IGF-1 positive cells in spinal dorsal horn was increased in group I2 ( P<0.05). There was no significant difference in the expression of spinal IGF-1R among the 4 groups ( P>0.05). Conclusion:Intrathecal IGF-1 can alleviate chemotherapy-induced NP, and the mechanism may be related to inhibiting the inflammatory responses in spinal cord of mice.
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Objective To evaluate the effect of pulsed radiofrequency (PRF) on the phenotypic transformation of the lumbar sympathetic ganglion (LSG) in the rats with diabetic neuropathic pain (PDN).Methods Twenty-four clean-grade healthy adult male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were divided into 4 groups (n =6 each) according to the method of random number table:control group (group C),group PDN,group PRF,and PRF control group (group PC).The PDN model was established by intraperitoneal injection of streptozotocin 60 mg/kg in anesthetized rats.Citrate-sodium citrate buffer 6 ml/kg was intraperitoneally injected in group C.Group PC only received radiofrequency needle puncture.PRF was performed on the right L3 LSG in group PRF.The mechanical paw withdrawal threshold (MWT) to yon Frey filament stimulation was measured before intraperitoneal injection (baseline,T0),before PRF and at 1,3,5,7 and 14 days after PRF.The rats were then sacrificed,and ipsilateral L3 LSGs were removed for determination of the expression of tyrosine hydroxylase (TH) and vesicle glutamate transporter2 (VGLUT2) in LSGs (by double immunofluorescent staining) and for examination of pathological changes (with a light microscope).The number of neurons expressing VGLUT2 was counted.Results Compared with group C,the MWT was significantly decreased at T1-6,and the number of neurons expressing VGLUT2 was increased at T6 in PDN,PC and PRF groups (P＜0.05).Compared with PDN and PC groups,the MWT was significantly increased at T2-6,and the number of neurons expressing VGLUT2 was decreased at T6 in group PRF (P＜0.05).TH expression in LSGs was found,and no VGLUT2 expression in LSGs was observed in group C,the expression of TH and VGLUT2 in LSGs was found in the other three groups,especially in PDN and PC groups,and most of the neurons expressing VGLUT2 expressed TH simultaneously.Conclusion The mechanism by which PRF mitigates PDN is related to inhibiting the phenotypic transformation of LSGs in the rats.
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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 investigate the effects of post-operative analgesia with oxycodone or morphine for patients undergoing colon cancer radical surgery on platelet activation and cellular immunity.Methods Forty colon cancer patients scheduled for radical surgery, 23 males and 17 females, ASA physical status Ⅰ or Ⅱ, were randomly divided into 2 groups (n=20 each): oxycodone group (group O) and morphine group (group M).Patient-controlled intravenous analgesia (PCIA) was used for post-operative analgesia.PCIA solution contained oxycodone 1 mg/kg and tropisetron 6 mg in 100 ml normal saline in group O or morphine 1 mg/kg and tropisetron 6 mg in 100 ml normal saline in group M.Blood samples were obtained from the patients at 5 min before anesthesia induction (T0), 4 h after surgery (T1), 24 h after surgery (T2) and 48 h after surgery (T3).The levels of glycoprotein (GP)Ⅱb/Ⅲa, P-selection (CD62P), natural killer (NK) cells, NKT cells, and natural Treg (nTreg) cells were detected.The platelet aggregation rate (PAR) was determined.Results Compared with T0, the levers of GPⅡb/Ⅲa, CD62P, PAR and nTreg cells were significantly higher at T1 in group O and at T1, T2 in group M (P<0.05).Compared with T0, the levels of NK and NKT cells were decreased significantly at T1 in group O and at T1-T3 in group M (P<0.05).The levels of GPⅡb/Ⅲa, CD62P, PAR and nTreg cells at T2 and T3 in group O were decreased significantly as compared with group M (P<0.05).The levels of NK cells, NKT cells at T2 and T3 in group O were significantly higher than those in group M.Conclusion Post-operative analgesia with oxycodone for patients undergoing colon cancer radical surgery exhibits a more significant effect of decreasing platelets activity and presents a less disturbance on cellular immunity as compared with morphine.
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Objective To evaluate the effects of sufentanil and morphine on cisplatin-induced acute kidney injury in rats.Methods Thirty-two healthy Sprague-Dawley rats, aged 8-10 weeks, weighing 220-280 g, were randomly divided into 4 groups (n =8 each) using a random number table: control group (group C);cisplatin group (group Cis);sufentanil group (group S);morphine group (group M).Cisplatin 16 mg/kg was injected intraperitoneally in group Cis.In group S, cisplatin 16 mg/kg was injected intraperitoneally, followed by injection of sufentanil 2 μg/kg over 5 min via the caudal vein for 3 consecutive days.In group M, cisplatin 16 mg/kg was injected intraperitoneally, followed by injection of morphine 2 μg/kg over 5 min via the caudal vein for 3 consecutive days.The equal volume of normal saline was given in group C.After the end of administration on 3rd day, blood samples were collected from the orbital venous plexus for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were then sacrificed, and the left kidney specimens were obtained for examination of the pathological changes (under the light microscope) and for determination of the tumor necrosis factor-alpha (TNF-α) , interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) concentrations (by enzyme-linked immunosorbent assay) , and expression of X-linked inhibitor of apoptosis protein (XIAP) , suvivin and caspase-3 (by Western blot).Periodic acid-Schiff's staining was used to evaluate the pathological changes of the renal tubule.Results Compared with group C, the serum BUN, Cr concentrations and renal tubule injury score were significantly increased, the contents of TNF-α, IL-1β and IL-6 were increased, the expression of XIAP and suvivin was down-regulated, and the expression of caspase-3 was up-regulated in Cis,S and M groups (P＜0.05).Compared with group Cis, the serum BUN and Cr concentrations and renal tubule injury score were significantly decreased, the contents of TNF-α, IL-1β and IL-6 were decreased, the expression of XIAP and suvivin was up-regulated, and the expression of caspase-3 was down-regulated in S and M groups (P＜0.05).There were no significant differences in the indexes mentioned above between group S and group M (P＞0.05).Conclusion Both sufentanil and morphine can reduce cisplatin-induced acute kidney injury in rats with similar efficacy, and the mechanism may be related to the inhibition of the inflammatory responses and cell apoptosis.
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Objective To evaluate the effects of curcumin pretreatment on the activity of inducible nitric oxide synthase (iNOS) during lung injury induced by intestinal ischemia-reperfusion (Ⅰ/R) in rats.Methods Twenty-four pathogen-free female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group Sham);intestinal Ⅰ/R group (group Ⅱ/R);curcumin pretreatment group (group Cur).A rat model of lung injury induced by intestinal Ⅰ/R which was produced by occlusion of superior mesenteric artery for 75 min followed by reperfusion was established.At 5 days before Ⅰ/R,curcumin 200 mg/kg (in 20 mg/ml of normal saline) was given through a gastric tube in group Cur,while the equal volume of normal saline was given instead in Sham and Ⅱ/R groups.The rats were sacrificed at 4 h of reperfusion,and the pulmonary specimens were obtained for determination of wet/dry lung weight ratio (W/D ratio),NO content (by using nitrate reductase method) and iNOS activity (using colorimetric method) and for examination of pathological changes (with light microscope).The pathological changes of the lung were scored.Results Compared with group Sham,the pathological scores,W/D ratio,NO content and iNOS activity were significantly increased in Ⅱ/ R and Cur groups.Compared with Ⅱ/R group,the pathological scores,W/D ratio,NO content and iNOS activity were significantly decreased in group Cur.The pathological changes of lungs were significantly attenuated in group Cur as compared with H/R group.Conclusion The mechanism by which curcumin pretreatment attenuates lung injury induced by intestinal Ⅰ/R is related to decrease in iNOS activity in rats.
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Objective To evaluate the effects of penehyclidine hydrochloride combined with ulinastatin on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty-eight patients of both sexes,aged 20-64 yr,weighing 40-66 kg,of ASA physical status Ⅱ (NYHA Ⅱ),scheduled for elective cardiac valve replacement with CPB,were randomly divided into 4 groups (n =12 each) using a random number table:control group (group C),penehyclidine hydrochloride group (group P),ulinastatin group (group U),and penehyclidine hydrochloride and ulinastatin group (group PU).Penehyclidine hydrochloride 0.02 mg/kg was injected via the right internal jugular vein at 15 min before induction of anesthesia in group P.In group U,the total amount of ulinastatin was 2× 104 U/kg,30％ of the total amount was given via the right internal jugular vein after induction and before surgery,40％ was added to the priming solution,and the remaining 30％ was injected via the right internal jugular vein while the aorta was opened.In group PU,penehyclidine hydrochloride or ulinastatin was given according to the method previously described in group P or U.The equal volume of normal saline was given instead in group C.After induction and before surgery (T1),at 30 min of CPB (T2),and at 30 min and 6 h after termination of CPB (T3,4),blood samples were taken from the left internal jugular bulb and radial artery for blood gas analysis and determination of jugular venous oxygen saturation,jugular venous O2 content,arterial O2 content,and plasma concentrations of S-100β protein and neuron-specific enolase (NSE) (by ELISA).Arteriovenous oxygen content difference (Ca-jrO2) and cerebral O2 extraction rate (CERO2) were calculated.Results Compared with group C,SjvO2 was significantly increased,and CERO2 was decreased at T2.3 in P and U groups and at T2.4 in group PU,and Ca-jvO2 and plasma concentrations of S-100β protein and NSE were decreased at T2,3 in P,U and PU groups.The plasma concentrations of S-100β protein and NSE were significantly lower at T2,3 in group PU than in P and U groups.Conclusion The combination of penehyclidine hydrochloride and ulinastatin produces better efficacy than either alone in attenuating brain injury in patients undergoing cardiac valve replacement with CPB.
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Objective To evaluate the effects of intrathecal TRESK gene recombinant adenovirus on inflammatory responses mediated by chemokine in the spinal cord of rats with neuropathic pain ( NP ) . Methods Thirty?six male Sprague?Dawley rats, weighing 200-250 g, were randomly divided into 6 groups (n=6 each) using a random number table: control group (group C); sham operation group (group S);NP group; TRESK?overexpressed adenovirus group ( group TRESK ); negative adenovirus group ( group Virus); normal saline group ( group NS) . Spinal nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats. In TRESK, Virus and NS groups, pAd∕CMV∕V5?DEST?TRESK 25 μl (109IU∕ml), negative adenovirus 25 μl and normal saline 25 μl were intrathecally injected, respectively. At 1 day before operation ( base?line, T0 ) and 1, 3, 7 and 14 days after operation ( T1-4 ) , the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency were measured. Six rats in each group were sacrificed after measurement of pain threshold at T3 . The L4,5 segments of the spinal cords were removed for determination of monocyte chemotactic protein?1 ( MCP?1) , MIP?2, tumor necrosis factor?alpha ( TNF?α) , interleukin?1 beta ( IL?1β) and IL?6 mRNA expression by real?time PCR. Results There was no significant difference in thermal paw withdrawal latency at each time point between groups. Compared with C and S groups, MWT at T1-4 in NP and TRESK groups and at T1-3 in Virus and NS groups were significantly decreased, and the expression of MCP?1, MIP?2, TNF?α, IL?1βand IL?6 mRNA was up?regulated in NP, TRESK, Virus and NS groups. Compared with group NP, MWT was significantly increased at T1-4, and the expres?sion of MCP?1, MIP?2, TNF?α, IL?1β and IL?6 mRNA was down?regulated in group TRESK. Conclusion The mechanism by which intrathecal TRESK gene recombinant adenovirus reduces NP is re?lated to inhibition of inflammatory responses mediated by chemokine in the spinal cord of rats.
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@#The aim of this study was to investigate the effect of polymers on the formation thermodynamics of adefovir dipifoxil(AD)-saccharin(SAC)cocrystal. In the absence and presence of polymers such as polyethylene glycol, ethyl cellulose, polyvinylpyrrolidone and Eudragit E100, solubilities of AD and SAC in ethanol solution containing different concentrations of SAC at variable temperatures were determined by high-performance liquid chromatography(HPLC). Appropriate mathematical model for the description of the influence of polymers and temperature on the solubility of AD-SAC cocrystal was established. The ternary phase diagrams were set up using the assayed solubilities data, and they were used to predict changes of cocrystals solubility and product yield. Addition of polymers resulted in increased solubility of AD-SAC cocrystal, decreased complexation constants(K11), enhanced solubility products(Ksp), but there was a gradually decreased free energy change(ΔG0). The areas of homogeneous liquid phase and pure solid cocrystal in equilibrium with the liquid phase in ternary phase diagrams were also found to be larger. Therefore, although there was no change to the spontaneity of AD-SAC cocrystal formation, there existed retardation to cocrystal formation and reduction in product yield of pure cocrystal in the presence of polymers. Moreover, application of polymers could broaden the concentration range of AD and SAC solutions when solution crystallization was selected to prepare cocrystal.
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Objective To evaluate the effects of curcumin preconditioning on the activity of xanthine oxidase (XOD) during intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty female Sprague-Dawley rats,aged 180-220 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (S group),intestinal I/R group (I/R group),and curcumin preconditioning group (Cur group).Intestinal I/R was induced by clamping the superior mesenteric artery for 75 min followed by reperfusion.Curcumin 200 mg/kg was given everyday for 5 days before intestinal I/R in Cur group and the equal volume of normal saline was given instead of curcumin in S and I/R groups.The rats were sacrificed at 4 h of reperfusion and the intestinal specimens were obtained for microscopic examination of pathologic changes which were graded using Chiu scoring system and for determination of XOD activity,content of malondialdehyde (MDA),and superoxide dismutase (SOD) activity.Results Compared with S group,the Chiu score,activity of XOD and content of MDA were significantly increased,while the activity of SOD was decreased in I/R and Cur groups (P ＜ 0.05).Compared with I/R group,the Chiu score,activity of XOD and content of MDA were significantly decreased,and the activity of SOD was increased in Cur group (P ＜ 0.05).Conclusion Curcumin preconditioning can attenuate intestinal I/R injury in rats,which may be due to inhibition of XOD activity and decreased oxidative stress in intestinal tissues.
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Objective To evaluate the effects of the right stellate ganglion block on the expression of β3adrenoceptor (β3-AR) in rabbits with heart failure.Methods Forty-eight Japanese white rabbits of both sexes,weighing 2.5-3.0 kg,were randomly divided into 3 groups (n =16 each):sham operation group (group S),heart failure group (group HF) and right stellate ganglion block group (group RSGB).Heart failure was induced by occlusion of left anterior descending branch of coronary artery and confirmed by ultrasonic cardiography 4 weeks later.A PE-10 catheter was inserted into the right stellate ganglion for administration of drugs.0.25％ bupivacaine 2 ml was injected through the catheter once a day for 2 weeks in group RSGB,while the equal volume of normal saline was injected instead of bupivacaine in S and HF groups.The left ventricular end-diastolic diameter (LVEDD),left ventricular end-systolic diameter (LVESD),ejection fraction (EF) and left ventricular fractional shortening (LVFS) were measured at 1 day before ligation (T0),before catheter insertion (T1),before 8th administration (T2),and 1 day after the last administration (T3).Eight rabbits were sacrificed at T1 and T3 in each group and myocardial specimens were obtained from the apex of the left ventricle for determination of the expression of β3-AR by Western blot.Results Compared with group S,the LVEDD and LVESD were significantly enlarged and LVEF and LVFS were decreased at T1-3,and the expression of β3-AR was up-regulated at T1,3 in groups HF and RSGB (P ＜ 0.05).Compared with group HF,the LVEDD and LVESD were significantly decreased,LVEF and LVFS were increased,and the expression of β3-AR was significantly down-regulated at T3 in group RSGB (P ＜ 0.05).Conclusion The right stellate ganglion block can improve the cardiac function of rabbits with heart failure through down-regulating the expression of β3-AR in myocardium.
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Objective To evaluate the role of C-Jun N-terminal kinase (JNK) signal transduction pathway in spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-260 g,were randomly divided into 6 groups (n =12 each):control group (group Ⅰ),sham operation group (group Ⅱ),JNK inhibitor group (group Ⅲ),dimethyl sulfoxide (DMSO) group (group Ⅳ),lidocaine group (group Ⅴ),and JNK inhibitor and lidocaine group (group Ⅵ).Group Ⅰ received no treatment.Intrathecal catheter was placed in the subarachnoid space in group Ⅱ.SP600125 25 μg and DMSO 20 μl were injected intrathecally in Ⅲ and Ⅳ groups,respectively.In group Ⅴ,10％ lidocaine 20 μl was intrathecally injected.SP600125 25 μg was injected intrathecally and 30 min later 10％ lidocaine 20 μl was injected intrathecally in group Ⅵ.Paw withdrawal threshold to yon Frey filament stimulation (PWT) and paw withdrawal latency to nociceptive thermal stimulation (PWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration,4 rats were randomly chosen from each group and sacrificed.Their lumbar enlargements were removed for determination of phosphorylated JNK (p-JNK) expression (using Western blot) and neuronal apoptosis (by TUNEL).The apoptotic index was calculated.Results Compared with group Ⅰ,no significant difference was found in MWT and TWL in Ⅱ,Ⅲ groups and expression of p-JNK in Ⅱ and Ⅳ groups (P ＞ 0.05),MWT at T2-4,6-8 and TWL at T2-4,7 in group Ⅴ and MWT at T2-6 and TWL at T2-5 in group Ⅵ were significantly increased,the expression of p-JNK was down-regulated and the apoptotic index was decreased in group Ⅲ (P ＜ 0.05),and the expression of p-JNK was up-regulated and the apoptotic index was increased in Ⅴ and Ⅵ groups (P ＜ 0.05).Compared with group Ⅴ,MWT and TWL were significantly decreased,the expression of pJNK was down-regulated and the apoptotic index was decreased in group Ⅵ (P ＜ 0.05).Conclusion Activation of JNK signal transduction pathway is involved in spinal neurotoxicity induced by lidocaine in rats possibly through promoting neuronal apoptosis in the spinal cord.
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Objective To compare the quality of emergence from TCI of sufentanil and remifentanil supplementing propofol-sevoflurane anesthesia in patients undergoing radical colo-rectal cancer resection.Methods Forty ASA Ⅰ or Ⅱ patients of both sexes aged 40-64 yr undergoing elective radical colo-rectal cancer resection were allocated into 2 groups ( n =20 each):sufentanil group (group S) and remifentanil group (group R).Anesthesia was induced with propofol TCI at plasma concentration (Cp) of 4.0 μg/ml in both groups and sufentanil TCI (effect-site concentration Ce =0.4 ng/ml ) or remifentanil TCI ( Cp =4.0 ng/ml).Tracheal intubation was facilitated with vecuronium 0.1 mg/kg.The patients were mechanically ventilated (VT =8-10 ml/kg,RR =12-16 bpm).PErCO2 was maintained at 30-40 mm Hg.Anesthesia was maintained with propofol TCI-sevoflurane supplemented with sufentanil (Ce=0.25 ng/ml) or remifentanil (Cp=2.5 ng/ml).The depth of anesthesia was maintained at Narcotrend index of 37-56 by adjusting Cp of propofol TCI and sevoflurane concentration.The infusion of sufentanil was discontinued at 40 min before the conclusion of the operation while remifentanil was administered until the end of surgery.The incidence of postoperative adverse events,the time from the end of operation to eye openg and the time to extubation were recorded.Reesults The two groups were comparable with respect to demographic data.Neither group developed prolonged emergence and respiratory depression but the time from the end of operation to eye opening and the time to extubation were significantly longer in group S than in group R.The incidence of hypertension and tachycardia,agitation,shivering aad coughing were significantly lower in group S than in group R.Conclusion The quality of emergence from sufentanil supplementing propofol-sevoflurane anesthesia is higher than that from remifentanil.
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ObjectiveTo investigate the role of T-type calcium channel in the spinal neurotoxicity of intrathecal (IT) lidocaine in rats.MethodsForty-eight adult male SD rats in which IT catheter was successfully implanted,weighing 230-270 g,were randomly divided into 4 groups ( n =12 each):dimethyl sulfoxide (DMSO)group (group D),lidocaine group (group L),mibefradil + lidocaine group (group M),normal saline + lidocaine group (group N).Another 12 rats served as control group (group C).DMSO and 10％ lidocaine 20μl were injected intrathecally in groups D and L respectively.After mibefradil 200 μg/10μl and normal saline 10 μl were injected intrathecally in groups M and N respectively,10％ lidocaine 20 μl was injected intrathecally in the two groups.The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before IT injection and at 2,4,8 and 12 h and 1,2,3,4 and 5 d after IT injection (T0-9).Four rats were sacrificed at T6 in each group and their lumbar enlargements were removed for microscopic examination.ResultsCompared with group C,no significant change in MWT and TWL was found at each time point in group D,MWT was significantly increased at T1-8 and TWL was significantly prolonged at T1-7 in groups L and N,and MWT was significantly increased at T1-6 and TWL was significantly prolonged at T1-6 in group M ( P ＜ 0.05 ).Compared with groups L and N,MWT was significantly decreased at T1-4 and TWL was significantly shortened at T1-4 in group M ( P ＜ 0.05).Pathological injury was significantly reduced in group M as compared with groups L and N.ConclusionT-type calcium channel is involved in the spinal neurotoxicity of IT lidocaine in rats.
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Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the neuronal damage induced by lidocaine.Methods SH-SY5Y cells were seeded in 96-well plates (100 μl/hole) with a density of 5 × 105/ml and randomly divided into 4 groups (n =63 each):normal culture group (C group),CaMK Ⅱ inhibitor KN93 (K group),lidocaine group (L group) and KN93 + lidocaine group (KL group).KN93 (final concentration 1 μmol/L) was added to the culture medium and the cells were then cultured for 24 h in group K.Lidocaine (final concentration 10 mmol/L) was added to the culture medium and the cells were then cultured for 24 h in group L.KN93 (final concentration 1 μmol/L) and lidocaine (final concentration 10 mmol/L) were added to the culture medium and the cells were then cultured for 24 h in group KL.The cell morphology was examined with microscope after 24 h of incubation.The viability of cells was measured by MTT assay before incubation and at 1,6,12 and 24 h of incubation.The apoptosis in the cells was assessed by flow cytometry.The apoptotic rate was calculated.Results Compared with C and K groups,the cell viability was significantly decreased and the apoptotic rate was increased in L and KL groups (P ＜ 0.05).The cell viability was significantly higher and the apoptotic rate was lower in group KL than in group L (P ＜ 0.05).There was no significant difference in the cell viability and apoptotic rate between C group and K group (P ＞ 0.05).The pathological changes were obviousin group L and significantly reduced in group KL.Conclusion CaMK Ⅱ is involved in the neuronal damage induced by lidocaine.
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Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the up-regulation of expression of Cav3.2 T-type calcium channels in spinal cord in a rat model of neuropathic pain (NP).Methods Forty-eight male Sprague-Dawley rats,aged 3 months,weighing 220-250 g,were randomly divided into 6 groups (n =8 each)∶ sham operation group (group S),group NP,dimethyl sulfoxide group (group D) and different concentrations of a specific CaMK Ⅱ inhibitor KN93 groups (groups K1-3).NP was produced by chronic compression of dorsal root ganglion.The rats in groups D and K1-3 received a single intrathecal injection of dimethyl sulfoxide and KN93 15,30,60 nmol/L (10 μl),respectively,on 5th day after NP.Paw withdrawal threshold to von Frey filament stimulation (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured before NP,before intrathecal injection on 5th day after NP,and at 30 and 60 min and 3,6 and 8 h after intrathecal injection on 5th day after NP (T1-7).The rats were sacrificed after the measurement of pain threshold at T7 and their lumbar enlargements were removed to detect the expression of Cav3.2 mRNA and protein using Western blot and RT-PCR.Results Compared with group S,MWT was significantly decreased,TWL was shortened and the expression of Cav3.2 mRNA and protein was up-regulated in NP,D and K1-3 groups (P ＜ 0.05).Compared with NP group,MWT was significantly increased,TWL was prolonged and the expression of Cav3.2 mRNA and protein was down-regulated in a concentration-dependent manner in K1-3 groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group D (P ＞ 0.05).Conclusion CaMK Ⅱ is involved in the development and maintenance of chronic NP by up-regulating the expression of Cav3.2 T-type calcium channels in rat spinal cord.
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ObjectiveTo establish a rat model of nerve damage induced by intrathecal(IT) lidocaine.MethodsFifty-five adult male SD rats weighing 200-220 g were randomly divided into 5 groups (n =11 each):group normal control (group C); group dimethyl sulfoxide (DMSO)-the solvent(group D) and groups IT 5％,10％,15％ lidocaine (groups L5.10.15 ).IT catheter was successfully implanted without complication in groups D,L5,L1o,L15.DMSO,5％,10％ and 15％ lidocaine 20 μl were injected IT in groups D,L5,L10,L15 respectively.Motor dysfunction of hindlimb was assessed and scored (0 =normal,2 =complete block) and paw withdrawal threshold to mechanical stimulation (von Frey filaments) (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured before (baseline) and at 1,2,3,4,5,7 d after IT administration in 8 animals in each group.Three animals in each group were sacrificed at 1 d after IT administration.The lumbar segment (L4-5) was removed for microscopic examination.ResultsThere was no significant difference in motor dysfunction score,MWT and TWL among groups C,D and L5.MWT was significantly increased and TWL prolonged at 1 and 2 d after IT administration in group L10,while in group L15 motor dysfunction score was significantly increased at 1,2 d after IT administration and MWT was significantly increased and TWL prolonged at 1,2,3 d after IT administration.There was significant histologic damage to spinal cord in groups L10 and L15.Conclusion Nerve damage can be induced by IT 10％ lidocaine.
RESUMEN
Objective To investigate the role of T-type calcium channel in lidocaine-induced neuronal cytotoxicity . Methods SH-SYSY cell line was a gift from cell biology laboratory of our medical university. The cells were cultured in DMEM liquid culture medium at 37℃ in incubator filled with 5% CO2 , and randomly divided into 4 groups ( n = 66 each) : control group (group C)and M, L and ML groups were exposed to 5 μmol/L mibefradil (a T-type calcium channel blocker), 10 mmol/L lidocaine and 5 μmoL/L mibefradil + 10 mmol/L lidocaine for 24 h. Cell morphology was examined by electronic microscopy at 24 h of drug exposure. Cell viability (by MTT) and neuronal apoptosis (by flow cytometry) were detected immediately before and at 1, 6, 12 and 24 h of exposure to mibefradil or/and lidocaine.Results In C and M groups, the cells demonstrated dendritic protrusions, enlarged nerve processes and dense lattice. After being exposed to lidocaine for 24 h, the dendritic protrusions disappeared,the cells decreased in size, shrinked and became round; the cell viability was significantly decreased while the neuronal apoptosis increased. The lidocaine-induced changes were significantly attenuated by co-incubation with mibefradil. ConclusionT-type calcium channel is involved in lidocaine-induced neuronal cytotoxicity.