Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients....Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.展开更多
BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPJ)is one of the most common procedures for the management of hallux rigidus.However,there is no consensus regarding outcomes following minimally invasiv...BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPJ)is one of the most common procedures for the management of hallux rigidus.However,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux rigidus.AIM To evaluate outcomes following MIDC for the management of hallux rigidus.METHODS During November 2023,the PubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux rigidus.RESULTS Six studies were included.In total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 months.The distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTPJ arthroscopy and debridement following MIDC.Retained intra-articular bone debris was observed in 100%of patients in 1 study.The weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of 87.1.The complication rate was 8.4%,the most common of which was persistent joint pain and stiffness.Thirty-two failures(8.7%)were observed.Thirty-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index procedure.CONCLUSION This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was recorded.The marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.展开更多
Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4...Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4 per group):in control group,rats received no treatment;in sham group,rats underwent a sham operation;in SDN group,rats underwent SDN with half of the dorsal penile nerve severed.The mating test was performed,and the intracavernous pressure(ICP)assessed six weeks after the surgical treatment.Results At postoperative six weeks,the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups(P>0.05),while the ejaculation latency(EL)was significantly longer and ejaculation frequency(EF)lower in the SDN group than in the control and sham groups(P<0.05).There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure(MAP)among the three groups(P>0.05).Conclusion SDN does not adversely affect the erectile function and sexual desire of rats,and at the same time it can reduce EL and EF,providing an application basis for SDN in the clinical treatment of premature ejaculation.展开更多
The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results...The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.展开更多
BACKGROUND Isolated capitate fractures are rare carpal fractures.Following high-energy injuries,capitate fractures are usually associated with other carpal fractures or ligament injuries.The management of capitate fra...BACKGROUND Isolated capitate fractures are rare carpal fractures.Following high-energy injuries,capitate fractures are usually associated with other carpal fractures or ligament injuries.The management of capitate fractures depends on the fracture pattern.Here,we report an unusual capitate fracture with a dorsal shearing pattern and concomitant carpometacarpal dislocation,with a 6-year follow-up.To the best of our knowledge,this fracture pattern and surgical management have not been previously reported.CASE SUMMARY A 28-year-old man presented with left-hand volar tenderness and decreased grip strength that persisted for one month after a traffic accident.Radiography showed a distal capitate fracture with carpometacarpal joint incongruence.Computed tomography(CT)revealed a distal capitate fracture with carpometacarpal joint dislocation.The distal fragment was rotated by 90°in the sagittal plane,and an oblique shearing fracture pattern was noted.Open reduction and internal fixation(ORIF)with a locking plate were performed using the dorsal approach.The imaging studies performed 3 mo and 6 years following surgery revealed a healed fracture,and the Disabilities of the Arm,Shoulder,and Hand and visual analog scale scores were significantly improved.CONCLUSION CT can detect capitate fractures with dorsal shearing pattern and concomitant carpometacarpal dislocation.ORIF using a locking plate are possible.展开更多
BACKGROUND We report a case with the displacement of an articular fracture fragment of the base of the second metacarpal from the ulnar to the volar side,treated via the dorsal approach.The dorsal approach can be a go...BACKGROUND We report a case with the displacement of an articular fracture fragment of the base of the second metacarpal from the ulnar to the volar side,treated via the dorsal approach.The dorsal approach can be a good option not only because it allows direct observation of ligament damage and fixation of bone fragments but also because the thin subcutaneous tissue makes the approach easier.CASE SUMMARY A 45-year-old man with a right hand injury visited the hospital.A small bone fragment was identified using plain radiography.Lateral radiography revealed the fragment as lying over the volar aspect of the carpometacarpal(CMC)joint.Computed tomography revealed that approximately one-third of the CMC joint surface of the second metacarpal was damaged.We provisionally diagnosed an intra-articular fracture with significant CMC joint instability and performed open reduction and internal fixation.We made a dorsal longitudinal incision over the CMC joint between the second and third metacarpals.The dorsal ligament of the third CMC joint was torn.We thought it had been dislocated to the volar side and spontaneously reduced to that position.There are only few reports of volar dislocation of CMC joint fractures,particularly of the second and third metacarpals;our report is unique as our patient had an intact interosseous ligament between the second and third metacarpals.CONCLUSION Although past reports have used a palmar approach,the dorsal approach is a good option for these cases.展开更多
Neck pain is common and has multiple sources, but correct diagnosis and matched treatment provide the best outcomes. The first description of ultrasound-guided dorsal scapular nerve blockade using a single-shot local ...Neck pain is common and has multiple sources, but correct diagnosis and matched treatment provide the best outcomes. The first description of ultrasound-guided dorsal scapular nerve blockade using a single-shot local anesthetic technique for the diagnosis and treatment of neck pain is reported. A 38-year-old female patient presented with neck pain, and the history and clinical examination strongly suggested myofascial pain affecting the middle scalene muscle. The pain had been unresponsive to pharmacological therapy or physiotherapy. After identifying the dorsal scapular nerve (DSN) in the body of the middle scalene muscle, an ultrasound-guided nerve block was performed using a single injection of local anesthetic to alleviate the patient’s pain. It has been demonstrated that the dorsal scapular nerve can be identified in the neck and effectively blocked using ultrasound guidance. This technique has the potential to assist in the diagnosis and treatment of neck pain originating from the middle scalene muscle.展开更多
This study evaluated the value of high-frequency ultrasonograpy for early detection of dorsal artery of foot in patients with type 2 diabetes mellitus (MD). Eighty subjects including 40 patients with type 2 MD (T2D...This study evaluated the value of high-frequency ultrasonograpy for early detection of dorsal artery of foot in patients with type 2 diabetes mellitus (MD). Eighty subjects including 40 patients with type 2 MD (T2DM group) and 40 healthy volunteers (NC group) were recruited. The intima-media thickness (IMT), the inner diameter and the perfusion of dorsal artery of foot were measured by using high-frequency ultrasonograpy. Meanwhile, the parameters of vascular elasticity, including stiffness parameter (]3), pressure-strain elastic modulus (Ep), arterial compliance (AC), augment index (AI), and pulse wave conducting velocity (PWV]3) were detected by means of echo-tracking technique. The results showed that no significant difference was found in the IMT, systolic diameter (Ds), diastolic diameter (Dd) and peak systolic velocity (PSV) between T2DM and NC groups. Ep and PWVβ were increased, and AC was decreased in T2DM group as compared with those in NC group with the differences being significant (P〈0.05 for all). There was no significant difference in β and AI between T2DM and NC groups. It was concluded that high-frequency ultra- sonography in combination with echo-tracking technique is sensitive and non-invasive, and can be used for early detection of sclerosis of the lower extremity artery in patients with type 2 MD.展开更多
AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separ...AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVCvagus-gastric neural pathway.展开更多
Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffectiv...Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10 μm/10 μm (even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 (groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1 (ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.展开更多
This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiife...This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.展开更多
Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, ce...Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.展开更多
The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regen...The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.展开更多
Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in t...Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid(AP-5),or both once daily for 15 days.Compared with injured drug na?ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity(as assessed by immunohistochemistry) and protein(as determined by western blot assay) in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.展开更多
The mechanism underlying the modulatory effect of substance P(SP) on GABA-activated response in rat dorsal root ganglion(DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clam...The mechanism underlying the modulatory effect of substance P(SP) on GABA-activated response in rat dorsal root ganglion(DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA(1–1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons(89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA(1–1000 μmol/L) evoked a depolarizing response in 236 out of 257(91.8%) DRG neurons examined with intracellular recordings. Application of SP(0.001–1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1(NK1) receptors antagonist spantide but not by L659187 and SR142801(1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C(PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca2+-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.展开更多
Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associa...Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons.To this aim,rats with persistent hyperalgesia were randomly divided into four groups.Rats in the control group received no treatment,and the rat sciatic nerve was only exposed in the sham group.Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide,an inhibitor of NKCC1,based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group.In the experiment measuring thermal withdrawal latency,bumetanide (15 mg/kg) was intravenously administered.In the patch clamp experiment,bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour,or bumetanide (5 μg/μL) was intrathecally injected.The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats.We found that the thermal withdrawal latency of rats was significantly decreased on days 7,14,and 21 after model establishment.After intravenous injection of bumetanide,the reduction in thermal retraction latency caused by model establishment was significantly inhibited.Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7,14,and 21 after model establishment.No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment.The Cl^– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl^– concentration in dorsal root ganglion neurons of chronic constriction injury model rats.We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl^– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment.The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased,and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment.After bumetanide administration,the above indicators were significantly suppressed.These results confirm that CCI can induce abnormal overexpression of NKCC1,thereby increasing the Cl^– concentration in dorsal root ganglion neurons;this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia.In addition,bumetanide can achieve analgesic effects.All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital,College of Medicine,Shihezi University,China on February 22,2017 (approval No.A2017-169-01).展开更多
Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to si...Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury(SNI)-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry(MS/MS). After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.展开更多
Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are compl...Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells (〉95%) using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly(lactic-co-glycolic acid)/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly(lactic-co-glycolic acid)/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
基金under a contract of the“Nicolás Monardes”program(RC-0002-2021)from the Andalusian Health Service,Andalusian Regional Ministry of Health and Consumptionfunds from the Excellent Project from Andalusian Government(Proy Excel_00996)+8 种基金funded by the French Multiple Sclerosis Foundation(ARSEP,1259&1254)the National Multiple Sclerosis Society(NMSS,RG 5088-A-1)the program“Investissements d’Avenir”(ANR-10-IAIHU-06 and ANR-11-INBS-0011–Neur ATRIS)under a“Miguel Servet”contract(CP20-0049)from the Health Institute CarlosⅢ,Ministry of Science and Innovation,Spainreceived grants from Andalusian Government and the European Commission under the Seventh Framework Program of the European Union(agreement Num.291730,contract TAHUB-II-107)ARSEP 1254IBRO Return Home FellowshipAES2022 from Health Institute CarlosⅢ(PI22/01141)the Excellent Project from Andalusian Regional Ministry of University,Research and Innovation(Proy Excel_00996)。
文摘Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.
文摘BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPJ)is one of the most common procedures for the management of hallux rigidus.However,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux rigidus.AIM To evaluate outcomes following MIDC for the management of hallux rigidus.METHODS During November 2023,the PubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux rigidus.RESULTS Six studies were included.In total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 months.The distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTPJ arthroscopy and debridement following MIDC.Retained intra-articular bone debris was observed in 100%of patients in 1 study.The weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of 87.1.The complication rate was 8.4%,the most common of which was persistent joint pain and stiffness.Thirty-two failures(8.7%)were observed.Thirty-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index procedure.CONCLUSION This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was recorded.The marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.
基金study was supported by Wuhan Application Foundation Frontier Project(No.2019020701011428).
文摘Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4 per group):in control group,rats received no treatment;in sham group,rats underwent a sham operation;in SDN group,rats underwent SDN with half of the dorsal penile nerve severed.The mating test was performed,and the intracavernous pressure(ICP)assessed six weeks after the surgical treatment.Results At postoperative six weeks,the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups(P>0.05),while the ejaculation latency(EL)was significantly longer and ejaculation frequency(EF)lower in the SDN group than in the control and sham groups(P<0.05).There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure(MAP)among the three groups(P>0.05).Conclusion SDN does not adversely affect the erectile function and sexual desire of rats,and at the same time it can reduce EL and EF,providing an application basis for SDN in the clinical treatment of premature ejaculation.
基金supported by the National Natural Science Foundation of China,Nos. 31730031 and 32130060the National Major Project of Research and Development,No. 2017YFA0104700the Natural Science Foundation of Jiangsu Province,No. BK20202013 (all to XSG)。
文摘The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.
文摘BACKGROUND Isolated capitate fractures are rare carpal fractures.Following high-energy injuries,capitate fractures are usually associated with other carpal fractures or ligament injuries.The management of capitate fractures depends on the fracture pattern.Here,we report an unusual capitate fracture with a dorsal shearing pattern and concomitant carpometacarpal dislocation,with a 6-year follow-up.To the best of our knowledge,this fracture pattern and surgical management have not been previously reported.CASE SUMMARY A 28-year-old man presented with left-hand volar tenderness and decreased grip strength that persisted for one month after a traffic accident.Radiography showed a distal capitate fracture with carpometacarpal joint incongruence.Computed tomography(CT)revealed a distal capitate fracture with carpometacarpal joint dislocation.The distal fragment was rotated by 90°in the sagittal plane,and an oblique shearing fracture pattern was noted.Open reduction and internal fixation(ORIF)with a locking plate were performed using the dorsal approach.The imaging studies performed 3 mo and 6 years following surgery revealed a healed fracture,and the Disabilities of the Arm,Shoulder,and Hand and visual analog scale scores were significantly improved.CONCLUSION CT can detect capitate fractures with dorsal shearing pattern and concomitant carpometacarpal dislocation.ORIF using a locking plate are possible.
文摘BACKGROUND We report a case with the displacement of an articular fracture fragment of the base of the second metacarpal from the ulnar to the volar side,treated via the dorsal approach.The dorsal approach can be a good option not only because it allows direct observation of ligament damage and fixation of bone fragments but also because the thin subcutaneous tissue makes the approach easier.CASE SUMMARY A 45-year-old man with a right hand injury visited the hospital.A small bone fragment was identified using plain radiography.Lateral radiography revealed the fragment as lying over the volar aspect of the carpometacarpal(CMC)joint.Computed tomography revealed that approximately one-third of the CMC joint surface of the second metacarpal was damaged.We provisionally diagnosed an intra-articular fracture with significant CMC joint instability and performed open reduction and internal fixation.We made a dorsal longitudinal incision over the CMC joint between the second and third metacarpals.The dorsal ligament of the third CMC joint was torn.We thought it had been dislocated to the volar side and spontaneously reduced to that position.There are only few reports of volar dislocation of CMC joint fractures,particularly of the second and third metacarpals;our report is unique as our patient had an intact interosseous ligament between the second and third metacarpals.CONCLUSION Although past reports have used a palmar approach,the dorsal approach is a good option for these cases.
文摘Neck pain is common and has multiple sources, but correct diagnosis and matched treatment provide the best outcomes. The first description of ultrasound-guided dorsal scapular nerve blockade using a single-shot local anesthetic technique for the diagnosis and treatment of neck pain is reported. A 38-year-old female patient presented with neck pain, and the history and clinical examination strongly suggested myofascial pain affecting the middle scalene muscle. The pain had been unresponsive to pharmacological therapy or physiotherapy. After identifying the dorsal scapular nerve (DSN) in the body of the middle scalene muscle, an ultrasound-guided nerve block was performed using a single injection of local anesthetic to alleviate the patient’s pain. It has been demonstrated that the dorsal scapular nerve can be identified in the neck and effectively blocked using ultrasound guidance. This technique has the potential to assist in the diagnosis and treatment of neck pain originating from the middle scalene muscle.
文摘This study evaluated the value of high-frequency ultrasonograpy for early detection of dorsal artery of foot in patients with type 2 diabetes mellitus (MD). Eighty subjects including 40 patients with type 2 MD (T2DM group) and 40 healthy volunteers (NC group) were recruited. The intima-media thickness (IMT), the inner diameter and the perfusion of dorsal artery of foot were measured by using high-frequency ultrasonograpy. Meanwhile, the parameters of vascular elasticity, including stiffness parameter (]3), pressure-strain elastic modulus (Ep), arterial compliance (AC), augment index (AI), and pulse wave conducting velocity (PWV]3) were detected by means of echo-tracking technique. The results showed that no significant difference was found in the IMT, systolic diameter (Ds), diastolic diameter (Dd) and peak systolic velocity (PSV) between T2DM and NC groups. Ep and PWVβ were increased, and AC was decreased in T2DM group as compared with those in NC group with the differences being significant (P〈0.05 for all). There was no significant difference in β and AI between T2DM and NC groups. It was concluded that high-frequency ultra- sonography in combination with echo-tracking technique is sensitive and non-invasive, and can be used for early detection of sclerosis of the lower extremity artery in patients with type 2 MD.
基金Supported by The National Nature Science Foundation Council of ChinaNo.81473784+3 种基金the Natural Science Foundation of Anhui ProvinceNo.1408085MH166the Natural Science Foundation of Anhui University of Traditional Chinese MedicineNo.2013qn002
文摘AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVCvagus-gastric neural pathway.
文摘Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10 μm/10 μm (even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 (groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1 (ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.
基金supported by the National Natural Science Foundation of China,No.81160158 and 30860290
文摘This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.
基金supported by the Hargreaves and Ball Trust,the National Institute for Health Research(II-LA-0313-20003)(to AJR)the Rosetrees Trust,the Academy of Medical Sciences,and the Manchester Regenerative Medicine Network(MaRMN)(to AF and AJR)Progetto Eccellenza from the Italian Ministry of Research(to VM)
文摘Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.
基金supported by the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.16KJA310005(to SYL)the Natural Science Foundation of Nantong City of China,No.JC2018058(to TMQ)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.
基金supported by the Youth Shihezi University Applied Basic Research Project of China,No.2015ZRKYQ-LH19
文摘Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid(AP-5),or both once daily for 15 days.Compared with injured drug na?ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity(as assessed by immunohistochemistry) and protein(as determined by western blot assay) in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.
基金supported by grants from the National Natural Science Foundation of China(No.30160026)the Youth Science and Technology Innovation Special Foundation of Xinjiang Production and Construction Corps,China(No.2010JC33)
文摘The mechanism underlying the modulatory effect of substance P(SP) on GABA-activated response in rat dorsal root ganglion(DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA(1–1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons(89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA(1–1000 μmol/L) evoked a depolarizing response in 236 out of 257(91.8%) DRG neurons examined with intracellular recordings. Application of SP(0.001–1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1(NK1) receptors antagonist spantide but not by L659187 and SR142801(1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C(PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca2+-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.
基金supported by the National Natural Science Foundation of China,No.30160026(to JQS)the High Level Talent Research Project of Shihezi University of China,No.RCSX201705(to YW)
文摘Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons.To this aim,rats with persistent hyperalgesia were randomly divided into four groups.Rats in the control group received no treatment,and the rat sciatic nerve was only exposed in the sham group.Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide,an inhibitor of NKCC1,based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group.In the experiment measuring thermal withdrawal latency,bumetanide (15 mg/kg) was intravenously administered.In the patch clamp experiment,bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour,or bumetanide (5 μg/μL) was intrathecally injected.The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats.We found that the thermal withdrawal latency of rats was significantly decreased on days 7,14,and 21 after model establishment.After intravenous injection of bumetanide,the reduction in thermal retraction latency caused by model establishment was significantly inhibited.Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7,14,and 21 after model establishment.No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment.The Cl^– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl^– concentration in dorsal root ganglion neurons of chronic constriction injury model rats.We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl^– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment.The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased,and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment.After bumetanide administration,the above indicators were significantly suppressed.These results confirm that CCI can induce abnormal overexpression of NKCC1,thereby increasing the Cl^– concentration in dorsal root ganglion neurons;this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia.In addition,bumetanide can achieve analgesic effects.All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital,College of Medicine,Shihezi University,China on February 22,2017 (approval No.A2017-169-01).
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2015RIDIAIA01059432)
文摘Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury(SNI)-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry(MS/MS). After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.
基金supported by the National Natural Science Foundation of China,No.30973060
文摘Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells (〉95%) using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly(lactic-co-glycolic acid)/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly(lactic-co-glycolic acid)/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.