Objective To investigate the sensory-discriminative and affective-motivational pain response of intrathecal injection of m-AIP,a special inhibitor of CaMKII,in a rat model of chronic constriction injury of sciatic nerve(CCI).Methods Eighteen SD rats were divided randomly into 3 groups(n=6):Group S(sham),Group C(control) and Group m-AIP.Group C and m-AIP were operated with the model of neumpathic pain induced by chronic constriction injury of sciatic nerve; Group S were treated as sham operated rats.Seven days after operation,Group S and C received intrathecal injection of 0.9％ NaCI 20 μl,while Group m-AIP received intrathecal injection of m-AIP 0.5 nmol/20 μl.Escape/avoidance behavior refrecting the affective-motivational dimension of pain was measured on 1.5 h after administration.Rats received pain behavior tests including paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) before and 2 h,4 h,8 h after administration.Results Treatment with m-AIP attenuated escape/avoidance behavior and reversed pain behaviors after CCI.At 2h and 4h after administration,Group m-AIP PWTL((1 1.45 ± 2.04)s,(10.26 ± 1.48)s) and PWMT ((21.15 ±4.32)g,(20.45 ±4.09) g) were increased when compared with Group C PWTL((9.63 ± 1.65)s,(9.30 ±0.73)s),PWMT((13.87 ±2.36)g,(14.80 ±3.12)g)(P＜0.05).Before and8 h after administration,Group m-AIP PWTL,PWMT had no significant difference when compared with Group C (P ＞ 0.05).Conclusion CaMKⅡ may play an important role in sensory and affective pain processing in neuropathic rats.Intrathecal injection of m-AIP can effectively improve pain behaviors and attenuate negative affect.

BACKGROUND: The repair of peripheral nerve defects by nerve conduit bridging can provide a suitable microenvironment for nerve regeneration. On one hand, it can provide a unique channel for nerve regeneration, prevent the invasion of peripheral connective tissue and the formation of scars. On the other hand, it can maintain endogenous and exogenous neurotrophic factors, growth factors and other stimulants to promote axon growth. OBJECTIVE: To observe the therapeutic effect of chitosan/polyvinyl alcohol catheter injected with brain-derived neurotrophic factor sustained-release microspheres to bridge peripheral nerve defects. METHODS: Chitosan/polyvinyl alcohol nerve conduit was prepared by repeated freeze-thaw technique. The brain-derived neurotrophic factor microspheres were obtained by polymer-alloys combined with oil-oil emulsion/solvent evaporation method. A 15 mm sciatic nerve defect model was made in the right hindlimb of 60 adult male Sprague-Dawley rats. They were selected and randomly divided into four groups (n=15 per group): group A implanted with autogenous sciatic nerve; group B implanted with chitosan/polyvinyl alcohol nerve catheter, injected with normal saline; group C implanted with chitosan/ polyvinyl alcohol nerve catheter, injected with brain-derived neurotrophic factor solution; group D implanted with chitosan/polyvinyl alcohol nerve catheter, injected with brain-derived neurotrophic factor sustained-release microspheres. General observation, histological inspection, and electrophysiological determination were performed at 4 months after the surgery. This study was approved by the Research Ethics Committee of the Second Hospital of Hebei Medical University. RESULTS AND CONCLUSION: (1) Gross anatomy showed that muscle atrophy in group A and group D was lighter than that in the other two groups. The grafts in four groups were all adhered to the peripheral tissues, and the nerve in the autotransplantation segment was strongly adhered to the peripheral tissues. In group D, the regenerated nerve had connected the distal and proximal nerves, and the regenerated nerve filled the conduit. (2) Electrophysiological examination showed that the latency of group D was shorter than that of groups B and C (P < 0.01), and the evoked potential and conduction velocity of group D were higher than that of groups B and C (P < 0.01). There was no significant difference between group D and group A (P > 0.05). (3) Histological observation showed that there were regenerated nerve fibers in groups B, C, and D. The diameter, number and thickness of myelin sheath of group D were larger than those of group B and group C (P < 0.01). There was no significant difference between group D and group A (P > 0.05). (4) The results showed that the injection of brain-derived neurotrophic factor microspheres into chitosan/PVA catheter had a long-term promoting effect on peripheral nerve regeneration.

Objective:To establish the best way of tumor-bearing nude mice model with epithelial ovarian adenocarcinoma cell lines. Methods:CAOV3 (wall-attached cell) and COC2 (suspended cell) cell lines were transplanted subcutaneously to the nude mice by injection with different cell concentration or tissue block implantation. Results:The rate and time of tumor formation in the two cell lines were not related to cell concentration in the range from 5?10 6/0.2 ml to 6?10 7/0.2 ml. Time of tumor formation was earlier(especially in the manner of tissue block implantation),the successful rate of tumor formation was higher and the speed of tumor growth was relatively retarded in the nude mice bore CAOV3 cell line's tumor than that in COC2 cell line's. But once tumors were formed in nude mice bearing COC2 cell line, the mice died too fast to make experiment because of very quick speed of tumor growth. Conclusion:Wall-attached cell line, tissue block implantation with trocar may be the best way to establish tumor-bearing nude mice model in epithelial ovarian adenocarcinoma cell lines.

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate (4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI).Methods Eighteen male SD rats were divided randomly into 3 groups(n=6):sham group (group S),CCI model group (group C0) and 4-CIN group (group C1).Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; and group S were treated as sham operated rats.Two days after operation,group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10％ DMSO 10 μl,while group C0 received intrathecal injection of 10％ DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d,3 d,7 d,10 d,14 d after operation(T0-5).Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5,the PWMT((11.71 ±2.81) g,(9.76± 1.00) g,(8.22± 1.33) g,(6.50± 1.48) g,(4.67± 1.03) g) and PWTL((11.36±2.18) s,(11.60±2.54) s,(8.54± 1.42) s,(7.59± 1.00) s,(6.88± 0.42) s) in group C0 were significantly lower than those in group S (P＜0.05).However,there were no significant differences between group S and C1 on T2-5(P＞0.05).Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI.

Objective To investigate the effects of repeated intrathecally kinesin superfamily protein 17 (KIF17) antisense oligodeoxynucleotide (ODN) on the expression of mLin10 and NR2B in spinal cord in a mouse model of bone cancer pain.Methods Fifty-six male C3H/HeJ mice,aged 4 ～ 6 weeks,weighting 20 ～ 25 g,were randomly divided into two groups:sham operation group (group S,n=20) and bone cancer pain group (group T,n=36).20μl α-minimal essence medium (α-MEM) which containing 2× 105 NCTC2472 osteosarcoma cells was injected into the intramedullary space of the right femur in group T.In group S,no cancer cell was instead.The number of spontaneous flinches (NSF) and the paw withdrawal mechanical threshold (PWMT) were measured at the day before (base) and the days 4,7,10 and 14 after inoculation.According to the corresponding time points,twenty-four mice were sacrificed for determination the expression of KIF17,mLin10 and NR2B using Western blot.Then,the mice of group T were randomly divided into three groups (n=8,T1,T2,T3,group).In group S and group T1,Saline 5 μl was injected intrathecally.KIF17 sense ODN and antisense ODN,5 μg/5μl were respectively injected in group T2 and T3 for 6 consecutive days.Pain behaviors were assessed at the days 2-6 after the first injection.And determinated the KIF17,mLin10 and NR2B expression,again.Results Compared with group S,the NSF was increased and the PWMT was decreased at the days 7,10 and 14 after inoculation in group T (P＜0.05).Compared with the base ((0.65±0.15),(1.06±0.06),(1.01±0.14)),the expression of KIF17,mLin10 and NR2B (14d:(1.13 ±0.06),(2.17 ± 0.37),(1.85 ± 0.32)) were increased at the days 7,10 and 14 after inoculation in group T(P＜0.05).During the course of the injection,compared with group T1 and T2,the NSF was decreased and the PWMT was increased significantly in the group T3(P＜0.05),the expression of KIF17,mLin10 and NR2B((0.88±0.08),(0.96±0.11),(1.03±0.08)) were reduced in group T3 (P＜0.05).Conclusion Intrathecal KIF 17 antisense ODN in the mice of bone cancer pain improves the pain behaviors,and inhibits the up-regulated of KIF17,mLin10 and NR2B during the course of the injection.

Objective To investigate the effect of recombinant human erythropoietin(rh-EPO) on the nerve regeneration of adult rats sciatic nerves. Methods Tirty-six healthy male Wistar rats were involved and left sciatic nerve repaired model was used.The experimental rats were divided randomly into two groups:the EPO group and the control group,18 rats in each group.rh-EPO 3 000 U/kg was injected daily into the abdominal in EPO group,and normal saline was injected into the abdominal every day after operation in control group.On 4 and 8 weeks after operation,these items were determined,the sciatic function index (SFI),biomechanics examination,histological observation,electrophysiological examination,myelinated fibers density and sectional area measurement.Results On weeks 4 after operation,the SFI of EPO group and control group were-65.26 ± 3.42 and-70.83 ± 4.12,respectively,the maximum tensile resistance were (3.86 ± 0.29)N/mm2 and (3.38 ± 0.21 )N/mm2,the delayed ratio of latency of motor nerve were 2.34 ± 0.23 and 2.78 ± 0.29,and the recovery ratio of wave amplitude were 0.23 ± 0.05 and 0.14 ± 0.03 respectively.On eight weeks after operation,the SFI of EPO group and control group were-51.34 ± 2.98 and-57.23 ± 4.86,respcetively,the maximum tensile resistance were (4.67 ± 0.36) N/mm2 and (4.13 ± 0.32) N/mm2,the delayed ratio of latency of motor nerve were 1.32 ± 0.15 and 1.62 ± 0.21,the recovery ratio of wave amplitude were 0.41 ± 0.09 and 0.26 ± 0.07,the nerve fibers cross ratio were 0.57 ± 0.05 and 0.38 ± 0.03,and the recovery ratio of sectional area of myelinated fibers were 0.81 ± 0.06 and 0.58 ± 0.03,respectively.Those items in EPO group were significantly superior to those in the control group (P ＜ 0.05 ＝.Conclusion rh-EPO can promote the injured nerve regeneration and improve the recovery of their function.

Objective To evaluate the role of neuron-restrictive silencer factor (NRSF) in the spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain (IP) .Methods Fifty-six male Kunming mice were randomly divided into 7 groups (n=8 each):control group (group C) ,IP group (group I) ,IP +remifentanil group (group IR ) , NRSF antisense oligonucleotide group (NAS group ) , IP + NRSF antisense oligonucleotide group (I+NAS group ) ,IP + remifentanil + NRSF mismatch oligonucleotide group (IR+NMS group) , and IP + remifentanil + NRSF antisense oligonucleotide group (IR + NAS group ) . Artificial cerebrospinal fluid 5 μl was injected intrathecally once a day for 3 consecutive days in C ,I and IR groups .NRSF antisense oligonucleotide NAS 10μg was injected intrathecally once a day for 3 consecutive days in NAS ,I+NAS and IR + NAS groups . NRSF mismatch oligonucleotide 10 μg was injected intrathecally once a day for 3 consecutive days in IR+NMS group .A 1-cm longitudinal incision was made through skin ,fascia and muscle of the plantar aspect of the right hindpaw to establish the model of incisional pain in sevoflurane-anesthetized rats .At 30 min after the last injection ,normal saline 0.4 ml was infused subcutaneously in C and NAS groups ,the model was established and normal saline 0.4 ml was subcutaneously infused simultaneously in I and I+NAS groups ,and the model was established and remifentanil 0.04 mg/kg was subcutaneously infused simultaneously in IR ,IR+NMS and IR+NAS groups .At 3 days before operation (T0 ) ,4 h before operation (T1 ) and 4 ,12 ,24 and 48 h after operation (T1-5 ) ,mechanical paw withdrawal threshold to von Frey stimuli (PMWT ) and paw withdrawal latency to thermal nociceptive stimulus (PTWL ) were measured .Results Compared with C group ,the PWMT and PWTL were significantly decreased at T2-5 in I ,IR ,I+NAS ,IR+NMS and IR+NAS groups ( P<0.05) ,and no significant change was found in the PWMT and PWTL at each time point in NAS group ( P>0.05 ) .Compared with I group ,the PWMT and PWTL were significantly decreased at T2-5 in IR and IR+NMS groups ( P<0.05) , and no significant change was found in the PWMT and PWTL at each time point in I +NAS group ( P>0.05) . Compared with IR group ,no significant change was found in the PWMT and PWTL at each time point in IR+NMS group ( P>0.05) ,and the PWMT and PWTL were significantly increased at T2-5 in IR+NAS group ( P<0.05) . Conclusion NRSF in the spinal cord is involved in the development and maintenance of hyperalgesia induced by remifentanil in a mouse model of IP .

Objective To evaluate the effects of different levels of neuromuscular blockade(NMB)on transcranial electric motor-evoked potentials(TCeMEPs)during idiopathic scoliosis.Methods Thirty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 11-23 yr,weighing 31-62 kg,scheduled for elective idiopathic scoliosis under general anesthesia,were enrolled in the study.NMB was monitored with train of four(TOF)-Watch SX.The levels of partial NMB were classified into 5 states according to TOF ratio(TOFR)and TOF counts:1 or 2 TOF counts(TOF1),3 TOF counts and TOFR≤15%(TOF2),TOFR 16%-25%(TOF3),TOFR 26%-50%(TOF4),TOFR 51%-75%(TOF5) and TOFR>75%(no NMB).Each state was maintained for 10 min.Failure and false-positive findings in TCeMEP monitoring,development of unexpected body movement and satisfaction with NMB were recorded.Results Compared with no NMB,the failure and false-positive rates of TCeMEP monitoring were significantly increased,the incidence of unexpected body movement was decreased,and the rate of satisfactory NMB was increased at TOF1,TOF2 and TOF3(P<0.05),no significant change was found in failure or false-positive rates of TCeMEP monitoring at TOF4 and TOF5(P>0.05),and the incidence of unexpected body movement was decreased and the rate of satisfactory NMB was increased at TOF4,the rate of satisfactory NMB was increased at TOF5(P<0.05),and no significant change was found in the incidence of unexpected body movement at TOF5(P>0.05).Compared with those at TOF4,no significant change was found in the failure or false-positive rates of TCeMEP monitoring(P>0.05),the incidence of unexpected body movement was significantly increased,and the rate of satisfactory NMB was decreased at TOF5(P<0.05).Conclusion Maintaining TOFR at 26%-50% the partial NMB during surgery does not affect TCeMEP monitoring during idiopathic scoliosis and meets the intra-operative NMB requirements simultaneously,and it is the optimum NMB for this type of surgery.

OBJECTIVE: To investigate the incidence rate and the risk factors for postoperative cognitive dysfunction (POCD) in patients underwent coronary artery bypass grafting surgery. METHODS: A total of 147 patients underwent elective coronary artery bypass grafting (CABG) surgery between January to July 2013 were included in this study. POCD was diagnosed using a neuropsychological test battery. All enrolled patients were interviewed on the day before surgery, the seventh day and 3 months after surgery, respectively, by the same researcher, and were divided into two groups based on the results: the POCD group and the non-POCD group. The information, including age, sex, body mass index, educational status, comorbidities, history of smoking and drinking, ASA grade, left ventricular ejection fraction, operation method, duration of operations, regional cerebral oxygen saturation, the lowest haemoglobin concentrations and the haemoglobin concentration decline rate during the operation, tracheal catheter retention time, postoperative pain on visual analogue scales (VAS) and systemic inflammatory response syndrome score (SIRS score), were recorded based on a schedule of survey. Multivariate logistic regression was used to analyze the risk factors for POCD. RESULTS: A total of 101 patients finished this study. On 7 days and 3 months after surgery, 38 and 21 cases showed POCD, with an incidence rate at 37.6% and 20.8%, respectively. Interestingly, there was no significant difference in incidence of POCD between CABG and OPCABG group on both 7 days and 3 months after surgery (P>0.05). The logistic stepwise regression analysis indicated that the risk factors for POCD included advanced age (OR=1.177, 95%CI 1.071-1.292, P=0.001), the haemoglobin concentration decline rate (OR=1.334, 95%CI 1.152-1.545, P<0.05) and SIRS score (OR=2.815, 95%CI 1.014-7.818, P=0.047). CONCLUSION The incidence rate of POCD was 37.6% and 20.8% on 7 days and 3 months after surgery respectively. Advanced age, the haemoglobin concentration decline rate and SIRS score are independent risk factors for POCD in patients underwent coronary artery bypass grafting surgery.
Age Factors ; Cognition Disorders ; epidemiology ; Coronary Artery Bypass ; adverse effects ; Hemoglobins ; Humans ; Incidence ; Logistic Models ; Neuropsychological Tests ; Pain Measurement ; Postoperative Complications ; epidemiology ; Risk Factors ; Systemic Inflammatory Response Syndrome

OBJECTIVE: To determine the changes of Mu-opioid receptor (Mor) and neuron-restrictive silencer factor (NRSF) in periaquductal gray (PAG) in mouse models of remifentanil-induced postoperative hyperalgesia. METHODS: Thirty-two Kun-Ming mice were randomly divided into 4 groups (8 mice in each group): Group C (mice underwent a sham procedure and saline was infused subcutaneously over a period of 30 min), Group I (mice underwent a surgical incision and the same volume of saline), Group R (mice underwent a sham procedure and remifentanil was infused subcutaneously at the moment of surgical incision over a period of 30 min), and group IR (mice underwent a surgical incision and remifentanil). Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) tests were performed 24 h before the operation and 2, 6, 24, and 48 h after the operation. The specimens were collected after behavioral testings at 48 h. The expressions of Mor and NRSF in mice's PAG neurons were determined by Western blot. RESULTS: Mechanical allodynia and thermal hyperalgesia developed in Group I, R and IR (P<0.01). Intraoperative infusion of remifentanil enhanced mechanical allodynia and thermal hyperalgesia in mice with planta incision (P<0.01). In Group R and Group IR, the expression of Mor was significantly lower (P<0.01) and NRSF was significantly higher (P<0.01) when compared with Group C and Group I. CONCLUSION Intraoperative infusion of remifentanil induces postoperative hyperalgesia in mouse models, accompanied with decreased expressions of Mor and increased of NRSF level in PAG neurons, which may be involved in remifentanil induced hyperalgesia.
Animals ; Disease Models, Animal ; Hyperalgesia ; chemically induced ; Mice ; Pain, Postoperative ; Periaqueductal Gray ; drug effects ; metabolism ; Piperidines ; administration & dosage ; Receptors, Opioid, mu ; metabolism ; Remifentanil ; Repressor Proteins ; metabolism