Volume 92  ·   Issue 07  ·  2012

In 2008, the International Association for Pain Research (IASP) Neuropathic Pain Professional Group revised the definition of neuropathic pain: "pain directly caused by damage or disease involving somatosensory system" [1]. However, in clinical work, the pathogenesis of neuropathic pain and the application of neuromodulation technology have not been widely recognized and paid attention to. We hope that this article will not only bring enlightenment and new knowledge to clinicians, but also arouse everyone's attention to this technology.

Objective To analyze the profiles of pressure pain threshold (PPT)and pressure pain tolerance (PTO) of healthy undergraduates so as to establish the normal reference ranges of PPT and PTO.Methods The levels of PPT and PTO were measured at lateral brachioradialis of lateral elbow joint with a pressure algometer in 113 healthy undergraduates.Then the influencing factors of tenderness thresholds were analyzed and the normal reference ranges of PPT and PTO established.Results The females exhibited a lower PPT than the males ( P ＜ 0.01 ).And the gender differences of PTO were statistically insignificant　( P ＞ 0.05 ).Meanwhile,there was no significant difference in either PPT or PTO between the right and left　sides (P ＞ 0.05 ).The normal reference ranges ( kg/cm2 ) of PPT and PTO were obtained at the measuring　spot of all subjects.As a result,the ranges of PPT were 1.19 - 4.63 in the males and 0.37 - 3.63 in the　females.And the range of PTO was 1.80 - 8.50 in all subjects.Conclusion This survey establishes the　normal reference ranges of tenderness thresholds at the specific measuring spot for some specific　population.These ranges may serve as a reference for the sensitivity of individual tenderness safely,accurately and simply.

Objective To explore the effects of α2 adrenergic receptor (α2AR) agonists clonidine and dexmedetomidine on the injury model of peripheral nerve chronic constriction in rats.Methods A total of 72 male SD rats weighing 180 -250 g were randomly divided into 4 groups (n =18 each).In sham operation group (S),the right sciatic nerves were exposed but not ligated.But,in other groups,four ligatures were placed around the right sciatic nerve according to the Bennett's method.From the instant after operation,0.4 mg · kg-1 · d-1 clonidine and 50.0 μg · kg-1 · d-1 were injected intraperitoneally into the clonidine group (CL) and dexmedetomidine group (Dex) daily.And the same volume of normal saline was injected into the S and CCI groups (C) respectively.Mechanical and thermal pain thresholds were measured by paw withdrawal latencies at Day 1 pre-operation and Day 3,7 and 14 post-operation.After that,the L4-6 dorsal root ganglions to chronic constriction injured sciatic nerves were harvested.Reverse transcriptionpolymerase chain reaction (RT-PCR) and agarose gel electrophoresis were used to examine the expression of GAP-43 mRNA.Results Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL)of groups C,CL and Dex markedly decreased and the expression of GAP-43 mRNA in dorsal root ganglions significantly increased at Days 3,7 and 14 post-operation versus those at pre-operation and group S ( P ＜0.05).TWL and MWT of groups CL and Dex at Days 7 and 14 post-operation significantly increased while the expression of GAP-43 mRNA in dorsal root ganglions markedly decreased versus those of group C (P ＜0.05).TWL and MWT of group Dex were significantly higher while the expression of GAP-43 mRNA in dorsal root ganglions was lower than those of group CL ( P ＜ 0.05 ).Compared with Day 3,TWL and MWT of groups C,CL and Dex markedly decreased while the expression of GAP-43 mRNA significantly increased in dorsal root ganglions at Day 7 (P ＜ 0.05 ).Compared with Day 7,TWL and MWT of groups CL and Dex markedly increased while the expression of GAP-43 mRNA in dorsal root ganglions significantly decreased at Day 14 (P ＜ 0.05).Conclusion Clonidine and dexmedetomidine both show evident analgesic effects on chronic neuropathic pain in rats probably through a reduction of nerve regeneration.But dexmedetomidine has a better efficacy due to of its high selectivity of α2AR.

Objective To explore the effects of cannabinoid 2 receptor (CB2) in the development of bone cancer pain in mice.Methods A total of 84 mice (C3H/HeJ) were randomly divided into 4 groups:tumor group ( Group T,n =30),medication administration group ( Group J,n =12),vehicle group ( Group D,n =12) and sham group ( Group S,n =30).And 2 × 105 osteolytic NCTC2472 cells in α-MEM were injected into medullary cavity of right distal femur to induce bone cancer pain in a murine model while sham mice received an injection of only α-MEM.All mice were tested for pain-related behaviors at preinoculation and at Days 5,7,10 and 14 post-inoculation.The tests included paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency ( PWTL).Group J and Group D were injected intrathecally with 2 μg JWH015 dissolved in 4％ DMSO and only 4％ DMSO respectively in a 5 μ1.volume.Pain behavior tests were performed before and at 1,6,24,48 and 72 h after an intrathecal injection.Lumbar intumescentia of mice in each group were harvested to examine the expression level of CB2by Western blot after pain behavior tests at Days 5,7,10 and 14 post-inoculation and 12 h after an intrathecal injection.Results (1) Pain behavior tests:Mechanical allodynia appeared at Day 7 postinoculation.The value of PWMT was ( 1.27 ± 0.28 ) g ( P ＜ 0.05 ) and it declined gradually to ( 0.53 ± 0.20) g at Day 14.The threshold of mechanical hyperalgesia increased to ( 1.00 ±0.20) g at 6 h after an intrathecal injection of JWH015,peaked at (1.40 ± 0.39) g at 12 h,became alleviated after 48 h and recovered to the pre-dosing levels at 72 h.Thermal hyperalgesia appeared at Day 10 post-inoculation.The value of PWTL was (16.9±0.4) s (P＜0.05) at Day 10 and declined to (11.5 ±0.7) s at Day 14 postinoculation.The threshold of thermal hyperalgesia increased to ( 15.7 ± 1.9 ) g at 6 h after an intrathecal injection of JWH015,peaked at ( 18.6 ± 2.3 ) g at 12 h,became alleviated after 48 h and recovered to the pre-dosing levels at 72 h.(2) Western blot:From Day 5 post-inoculation,the ratio of CB2/β-actin increased gradually.Compared with the ratio of 0.190 ± 0.010 at Day 5 post-inoculation,the ratio of CB2/β-actin increased to 0.660 ± 0.010 at Day 14 post-inoculation ( P ＜ 0.05 ) ; compared with the ratio of 0.903 ±0.006 in group D at 12 h after an intrathecal injection of JWH015,the ratio of CB2/β-actin 0.510 ±0.010significantly decreased (P ＜ 0.05).Conclusion The cannabinoid 2 receptor plays an important role in the formation of bone cancer pain.

Objective To investigate the change in glycogen synthase kinase-3β (GSK-3[β) in spinal cord neurons in rats with incisional pain (IP)- remifentanil-induced hyperalgesia.Methods 32 SD male rats(240- 260 g) were randomly divided into 4 groups (n =8 each):group R,group I,,group R + I and group C.IP was established as Brennan' s description.Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured 24h before anesthesia and 2,6,24,48 h after anesthesia.The rats were sacrificed after the last threshold measurement.The expressions of GSK-3β mRNA in rats' spinal cord neurons were determined by real-time PCR.The expressions of GSK-3β and pGSK-3β in rats' spinal cord neurons were determined by Western blot.Results Remifentanil-induced hyperalgesia developed in group R,I and R + I.The expression of GSK-3β mRNA and the expression of GSK-3β in rats' spinal cord neurons were highest in group R + I.In addition,the ratio of pGSK-3 β/GSK-3 β was smallest in group R + I.Conclusion These data indicate that the increased GSK-3β activity in rats spinal cord neurons is involved in remifentanil-indüced hyperalgesia.

Objective To explore the magnetic resonance imaging (MRI) manifestations of pancreatic neuroendocrine carcinoma (PNC).Methods The clinical data of 7 PNC patients as confirmed by pathological examination were analyzed retrospectivelyand the relevant literatures discussed. Results Among them,2 patients were misdiagnosed for benign tumor lesion,one for SPT and another for pancreatic cancer with liver metastasis.And 3 were diagnosed correctly.The lesions showed irregular or lobulated shapes:5 in body and tail of pancreas and 2 in head of pancreas.All lesions were hypointense on T1 WI.They were iso- to slightly hyperintense ( n =5 ) and heterogeneously hyperintense ( n =2 ) on T2WI.Dynamic contrast-enhanced MRI was performed in all.There were slight enhancement (n =2 ) and moderate enhancement ( n =5 ) during arterial phase.During interstitial and delayed phases,there were gradual enhancement (n =2) and less enhancement (n =5) than pancreatic parenchyma.There were metastasis of lymph nodes ( n =1 ),splenic metastasis ( n =2 ),liver metastasis ( n =1 ) and invasion of pancreatic capsule (n =3 ).Conclusion Due to the lack of MRI specificities,a definite diagnosis of pancreatic neuroenducrine carcinoma must be made by pathological examination and immunohistochemisty.

Objective To summarize the clinical experiences of normal saline pressed injection via lumbar puncture in the treatment of acute tonsillar hernia induced apnea.This procedure was routinely carried out after external ventricular drainage and/or lesion removal via open craniotomy.Methods During the period of 1969 to 2005,a total of 43 patients failed to regain respiratory after external ventricular drainage using rapid small hole cranio-puncture apparatus or lesion removal via open craniotomy.They underwent lumbar puncture and normal saline was pressed injected via a lumbar puncture needle.The patient data were retrospectively analyzed.Results Eleven of 43 patients had spontaneous respiration and fully recovered (25.6％ ),16 patients regained respiration but died eventually (37.2％ ) and 16 patients failed to regain respiration ( 37.2％ ).The effective rate was 62.8％.Conclusion For the patients failing to regain respiration after external ventricular drainage or supratentorial lesion removal via open craniotomy,the conservative treatment should not be the first choice.The pressed injection of normal saline via lumbar puncture may rescue some patients.

Objective To explore the treatment strategies for complicated craniocervical junction malformations with diverse clinical and imaging features.Methods The clinical data of 67 cases of complicated craniocervical junction malformation treated between January 2000 to December 2010 were retrospectively analyzed.Based on their clinical maniféstations and imaging findings,different operative procedures were adopted,including odentoidectomy via transoral transpharyngeal approach (n =3 ),occipito-cervical fusion and (or) suboccipital decompression ( n =19 ) and odentoidectomy via transoral transpharyngeal approach followed by occipito-cervical fusion in two-stage operation ( n =25 ).Four cases underwent merely odentoidectomy via transoral transpharyngeal approach and died postoperatively.Sixteen cases had occipito-cervical fusion and (or) transorally surgical release for reduction in one stage.Results Clinical symptoms significantly improved in 19 cases,partially improved in 21 cases and remained unchanged in 12 cases.Nine cases deteriorated postoperatively and 6 cases died.The effective rate was 59.7％.Conclusion The complexity of craniocervical junction malformations may be fully assessed based on different clinical manifestations and thorough imaging studies.Then personalized operative plans are to be designed.

Objective Untreated ruptures of anterior cruciate ligament (ACL) lead to progressive meniscus tear and development of knee osteoarthritis over decades.The present study was designed to explore the early results of ACL reconstruction for the patients with unstable ACL-deficient knee with osteoarthritis.Methods Twelve patients with a mean age of 46 years (range:35 -54) underwent ACL reconstruction for ACL-deficient knee with osteoarthritis.All had chronic anterior instability and one or more episodes of knee instability.There was no previous diagnosis of ACL ruptures and no prior ligament surgery on involved knee.The preoperative duration of symptoms was 1 to 5 years.ACL reconstruction with arthroscopic single-bundle four-strand hamstring tendon autograft was performed for all patients.The laxity of knee was determined with Lachman and pivot tests.The patient subjective evaluation of function was examined with the modified Lysholm scoring scale pre- and post-operatively.Results Obvious articular cartilage degeneration and cartilage space stenosis in medial compartment were found in 9 patients and complex medial meniscus tear in 10.During the follow-up period of 9 -36 months,there was no graft failure or loss of ROM ( range of motion) for any of these knees.The symptoms of instability were relieved in all patients.The post-operative knee stability improved markedly.The modified Lysholm scores improved from a median pre-operative score of 62.0 points to an average of 89.5 at the last follow-up.Conclusion ACL reconstruction with hamstring tendon may significantly relieve symptoms and improve knee functions in the patients of chronic anterior cruciate ligament-deficient knee with osteoarthritis,especially in those with primary symptoms of instability.

Objective To explore the clinical manifestations and surgical strategies of scoliosis associated with syringomyelia.Methods A total of 50 cases diagnosed as scoliosis with syringomyelia between January 2003 and November 2010 were recruited.They were divided into 2 groups:Group A,neurosurgery before scoliosis correction,including suboccipital decompression and syrinx shunting; Group B,one-staged posterior correction and instrumentation without previous neurosurgery.The preoperative,postoperative and last follow-ups of Cobb angle of coronal main curve and thoracic kyphosis were measured.Also the preoperative and postoperative apical vertebra translation,apical vertebra rotation and trunk shift were measured by the same person.The surgical efficacies and complications of correction were compared between 2 groups.Results All patients underwent posterior pedicle screw instrumentation and had a meam follow-up period of 32.1 months.Among them,42 patients had clinical symptoms or signs preoperatively and 3 patients improved postoperatively.The mean correction of coronal curve was 65.7％ and a mean loss of correction 6.4％ during the follow-up.The mean correction of apical vertebra translation and apical vertebra rotation were 63.0％ and 60.0％ respectively.However,the trunk shift increased 0.4 cm.There were no statistically significant differences for the correction efficacies and complications between 2groups (P ＞ 0.05).Conclusion Scoliosis associated with syringomyelia may be effectively managed if a surgeon manipulates carefully intraoperatively and perioperative spinal monitoring is practiced.Furthermore syrinx will not increase the incidence of postoperative complications without prophylactic neurosurgery.

Objective To explore the differences of working memory task performance between male patients with heroin dependence in methadone maintenance treatment (MMT) and healthy controls (HC).Methods A total of 42 heroin-dependent patients at Huainan City Psychiatric Hospital from May 2011 to October 2011 were compared with 31 gender- and age-matched HCs on such working memory tests as visualspace,visual-verbal and visual-face.Then the accurate rate and reaction time of the above tasks were between two groups.Results The participants with anxiety or depression were excluded.All MMT subjects were required to have negative urine toxicology screening tests.The accurate rate of verbal working memory of the patients was worse than that of HCs (83％ ±9％ vs 89％ ± 10％ ).And the difference was significant between two groups ( t (71) =- 2.631,P =0.010).The accurate rate of visual-object and visual-spatial working memory showed no significant differences between two groups ( P ＞ 0.05 ).The differences in reaction time on these tasks showed no statistical significance between two groups ( P ＞ 0.05 ).In addition,the dose of methadone and the duration of MMT revealed no significant effects on the performance of working memory and executive functions.Conclusion The disproportion impairment of patients on space,verbal and face working memory is probably due to the differential heroin-mediated injuries of encephalic regions.Methadone has no effect on working memory and executive functions in the patients with a history of heroin use during maintenance treatment intervention.

Objective To explore the expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus (SLE).Methods Thirty active SLE patients (including 17 SLE patients with lupus nephritis),20 inactive SLE patients and 20 healthy controls were enrolled.The expressions of Th17 cells and CD4 + CD25 + Foxp3 + Treg cells in peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry.The correlations between the expression of Th17 cells,CD4 + CD25 + Foxp3 + Treg cells and disease activity (SLEDAI),as well as the ratios of Th17 cells and Treg cells (Th17/Treg) in SLE patients and healthy controls were analyzed respectively.Results The expression of Th17 cells in PBMC of SLE patients was higher than that in healthy controls [ ( 1.39 ± 0.60)％ vs (0.80 ± 0.33 )％,P ＜ 0.01 ] while the expression of CD4 + CD25 + Foxp3 + Treg cells decreased in SLE patients [ (3.09 ± 1.54) ％ vs (6.04 ± 1.49) ％,P ＜ 0.01 ].The increased expression of Th17 cells and reduced CD4 + CD25 + Foxp3 + Treg cells in PBMC were positively correlated with SLEDAI and negatively correlated with complements C3 and C4.There were increased expression of Th17 cells and reduced CD4 + CD25 + Foxp3 + Treg cells in PBMC of lupus nephritis versus SLE patients without nephritis.Conclusion There is an abnormal elevation of Th17 cells and decrease of CD4 + CD25 + Foxp3 + Treg cells in PBMC of SLE patients.The imbalance between Thl7 and Treg cells may play a critical role in the pathogenesis of SLE.

Objective To detect the conduction block (CB) between nerve root and Erb's point by triple stimulation technique (TST) in patients with multifocal motor neuropathy (MMN).Methods The subjects were recruited from Peking University Third Hospital during the period of April 2010 to April 2011.Twelve MMN patients,30 healthy subjects,30 patients with cubital tunnel syndrome and 30 patients with amyotrophic lateral sclerosis (ALS) underwent TST along with clinical assessments and nerve conduction studies.TST combined transcranial magnetic stimulation (TMS) of motor cortex with peripheral collision studies.The results were expressed by the TST amplitude ratio.And the conduction block was judged by TST amplitude ratio or the amplitude ratio of compound muscle action potential (CMAP).Results The TST amplitude ratio of healthy volunteers was 93.0％ ±2.7％.And it was 42.3％ ±7.1％ in patients with MMN indicating a proximal CB.There were 47 CBs in distal segments by routine nerve conduction study.Compared with the baseline levels,the patients with definite MMN increased (x2 =6.31,P ＜ 0.05 ).The TST amplitude ratio(30.5％ ± 4.8％ )of those with ALS indicated the lesion of pyramid tract (t =2.43,P ＜ 0.05).And the TST amplitude ratio ( 92.2 ％ ± 2.6％ ) of those with cubital tunnel syndrome was normal( t =0.68,P ＞ 0.05 )while the nerve conduction velocity of cubital tunnel syndrome patients (below elbow-above elbow) was slower( (23.6 ± 3.5) m/s) ( t =2.00,P ＜ 0.05).Conclusion TST may be used to detect proximal CB and facilitate the diagnosis of MMN.

Objective To evaluate the clinical efficacy and safety of intravenous panipenembetamipron in the treatment of hematological malignancies infections.Methods From October 2009 to December 2010,a total of 286 hematological malignancy infection patients were recruited into this openlabel,perspective and multicenter clinical trial to receive an intravenous daily dose panipenem-betamipron of 0.5 g every 6 or 8 hours for 7 - 14 days.All clinical change and adverse reactions were recorded.Results The total effective rate of panipenem-betamipron in the treatment of hematological malignancy infections was 86.6％ (206/238).The effective rates of septicemia,pulmonary infections, urinary tract infections,digestive canal infections,oral infections and other infections were 68.2％ ( 15/22),89.3％ ( 100/112),77.8％ (14/18),100％ (22/22),83.3％ (10/12) and 86.5％ (45/52) respectively.The overall bacterial eradication rate was 85.07％ (57/67) and the rate of adverse reactions 5.9％(17/286). Conclusion Panipenem-betamipron is both safe and effective in the treatment of hematological malignancy infections.

Objective To compare the axonal transport of wild-type (WT) and K141N mutant HSP22 in transfected primary cultured cortical neurons.Methods The plasmid (pCAGGS-HA-wtHSP22 or pCAGGS-HA-K141NHSP22) with WT or K141N mutant HSP22 gene and a GFP-expressing plasmid ( pEGFP-N1 ) were co-transfected respectively into primary cultured cortical neurons.The axonal transport of WT and K141N mutant HSP22 was observed.And the distance traveled by WT and K141N mutant HSP22 was analyzed.Results The WT HSP22 was transported within axons and uniformly present throughout the entire length of axons.K141N mutant HSP22 failed to be transported to the same extent and was present only in cell body and proximal portion of axons.Analysis of distance traveled revealed that WT HSP22 traveled significantly further than the K141N mutant HSP22.Conclusion The axonal transport of K141N mutant HSP22 may play an important role in the pathogenesis of CMT2L.

Objective To directly inject recombinant pcDNA3.1-VEGF165 plasmid into degeneration interverbral disc and explore its effects on vascular buds of vertebral cartilage endplate and intervertebral disc in rabbits.Methods Rabbits were randomly assigned into the experimental and control groups (n =10 each).For the experimental group,the animals were anesthetized and the front vertebral body exposed.With the longitudinal ossature of front vertebral body of lumbar vertebrae as a mark,a needle was inserted at the central point of the front fourth and fifth lumbar intervertebral disc and 20 μl pcDNA3.1-VEGF165 injected.For the control group,20 μl pcDNA3.1 was injected.At Weeks 4 and 8 post-injection,the changes of vertebral cartilage endplate were monitored by radiograph,histology and scanning electron microscopy.Results The vertebral cartilage endplate calcification and degeneration in the experimental group were less pronounced than that in the control group at Week 8 post-operation.The average number and diameter of vascular buds obviously increased in the experimental group at Weeks 4 and 8 post-operation.The number and diameter of vascular buds in the region of inner annulus increased compared with those in the area near nucleus pulposus.Conclusion The pcDNA3.1-VEGF165 plasmid may promote the vascular buds of vertebral cartilage endplate by increasing their average number and diameter and arresting the intervertebral disc degeneration.

Objective To explore the feasibility of disrupting tumor microcirculation by the cavitation of microbubbles enhanced ultrasound (US) and analyze its pathological mechanism.Methods Twenty-four SD male rats with subcutaneously transplanted Walker-256 tumor were divided into 3 groups,i.e.ultrasound plus microbubbles group (US + MB),US group and sham group.Pulsed US was delivered to tumor for 3 minutes during an intravenous infusion of microbubbles at 0.2 ml/kg in the US + MB group.The control groups received only the US exposure or the MB injection.Tumor perfusion was visualized with contrast enhanced ultrasound before and 0 ain after treatment.Finally the pathological examination was performed.Results The contrast perfusion of Walker-256 tumors vanished immediately after treatment in the US+ MB group and the gray scale value (GSV) decreased from 121 ±12 (pre-treatment) to 81 ±9 (posttreatment,P ＜0.01 ).There was no significant difference of GSV before and after treatment in two control groups (P ＞0.05).The GSV values were 112 ± 14 and 111 ± 12 pre-treatment and 113 ± 14 and 103 ± 13post-treatment in the sham and US groups.The pathological examination showed remarkable hemorrhage,endothelial injuries,increased intercellular edema and in situ thrombosis.Conclusion Microbubbleenhanced ultrasound can significantly disrupt tumor vasculature and block its circulation.And it may become a novel physical anti-angiogenetic therapy for tumor.

Epilepsy in which seizures are difficult to control with medication is called refractory epilepsy, and about 50% of them are assisted in localization by finding characteristic discharges in some areas of origin of seizures, Such as electrical attenuation mode, low amplitude fast activity, etc. [1].

Regarding the prevention of hepatitis B recurrence after hepatitis B virus-related liver diseases (HBRLD) liver transplantation, it is recognized that the best scheme at home and abroad is nucleoside analogue combined with high-titer hepatitis B immunoglobulin (HBIG) [1-2]. However, there are many disadvantages in long-term use of HBIG [3-4]. Therefore, many liver transplantation centers at home and abroad are conducting research on hepatitis B vaccination after HBRLD liver transplantation, hoping to induce the body to produce sufficiently high titer of endogenous protective antibody (anti-HBs) to replace HBIG. However, due to the different inclusion criteria of vaccination objects, judgment criteria for success of vaccination, vaccine types and vaccination schemes adopted by each research center, the success rate of vaccination is also very different. This paper summarizes the related issues of hepatitis B vaccination after HBRLD liver transplantation, in order to provide reference and help for future work.