AIM:To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H.pylori) positive chronic gastritis before and after eradication.METHODS:Gastric biopsy samples were obtained from corpus and antru...AIM:To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H.pylori) positive chronic gastritis before and after eradication.METHODS:Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H.pylori positive chronic gastritis (n=18) before and after eradication.Tradi-tional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examina-tions were carried out.Immunohistochemistry for cap-saicin receptor (TRVP1),calcitonin gene-related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab VisionCo.,USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd.,UK).RESULTS:Eradication treatment was successful in 16 patients (89%).Seven patients (7/18,39%) re-mained with moderate complaints,meanwhile 11 pa-tients (11/28,61%) had no complaints.At histological evaluation,normal gastric mucosa was detected in 4 patients after eradication treatment (4/18,22%),and moderate chronic gastritis could be seen in 14 (14/18,78%) patients.Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls,89% (16/18,P < 0.001) in patients before and 72% (13/18,P < 0.03) after eradication.CGRP was positive in 40% (8/20) of controls,and in 100% (18/18,P < 0.001) of patients before and in 100% (18/18,P < 0.001) after eradication.The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy con-trols,and in 5.5% (3/18,P > 0.05) of patients before and in 0% of patients (0/18,P > 0.05) after H.pylori eradication.CONCLUSION:Distibution of TRVP1 and CGRP is altered during the development of H.pylori positive chronic gastritis.The immune-staining for TRVP1,CGRP and SP rwemained unchanged before and after H.py-lori eradication treatment.The capsaicin-sensitive affer-entation is an independent from the eradication treat-ment.The 6 wk time period might not be enough time for the restituion of chronic H.pylori positive chronic gastritis.The H.pylori infection might not represent the main pathological factor in the development of chronic展开更多
Endoscopic ultrasound-guided gastroenterostomy(EUS-GE)has emerged as an effective and minimally invasive alternative for treating gastric outlet obstruction.Compared to traditional options,including duodenal stenting ...Endoscopic ultrasound-guided gastroenterostomy(EUS-GE)has emerged as an effective and minimally invasive alternative for treating gastric outlet obstruction.Compared to traditional options,including duodenal stenting and surgical gastrojejunostomy,EUS-GE offers comparable technical and clinical success while providing longer-lasting patency,fewer adverse events,and lower reintervention rates.The technique has expanded beyond malignant obstruction to include benign etiologies and complex conditions such as afferent loop syndrome.EUSGE enables rapid recovery and early resumption of oral intake,which is crucial for oncologic patients.However,the procedure remains technically demanding,and optimal techniques,device selection,and management of complications are still under investigation.This mini-review summarizes current evidence,compares EUS-GE with alternative therapies,discusses patient selection and procedural aspects,and outlines key areas for future research.展开更多
Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental pati...Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.展开更多
Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of...Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system.展开更多
Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acu...Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acupuncture has a benign adjustment effect on gastrointestinal(GI) movement;however, the mechanism of this effect is unclear, especially in terms of neural mechanisms, and there are still many areas that require further exploration. This article reviews the recent data on the neural mechanism of acupuncture on GI movements. We summarize the neural mechanism of acupuncture on GI movement from four aspects: acupuncture signal transmission, the sympathetic and parasympathetic nervous system, the enteric nervous system, and the central nervous system.展开更多
Objective:The age-related change is important part of degenerative disc disease. However,no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of interver...Objective:The age-related change is important part of degenerative disc disease. However,no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods:22-month-old Sprague-Dawley(SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types II and X was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed. Results:There were less collagen type II expression and more collagen type X expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased,compared with that of the young control group(P<0.01) . Conclusion:Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types II and X,numbers and areas of afferent vascular buds,the ratio of the non-calcified to the calcified layers,and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.展开更多
The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and tran...The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli.Acupuncture-like signals were elicited in PANs using three techniques:manual acupuncture(MAc),emulated acupuncture(EAc),and electro-acupuncture(EA)-like peripheral electrical stimulation(PES).The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz,respectively.The frequency of discharges in PANs was correlated with the frequency of PES.The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers.Therefore,EA in a dense-disperse mode(at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc.Frequencies of EA output>250 Hz appear to be obsolete for pain relief.展开更多
Afferent loop obstruction is a purely mechanical complication that infrequently occurs following construction of a gastrojejunostomy. The operations most commonly associated with this complication are gastrectomy with...Afferent loop obstruction is a purely mechanical complication that infrequently occurs following construction of a gastrojejunostomy. The operations most commonly associated with this complication are gastrectomy with Billroth Ⅱ or Roux-en-Y reconstruction, and pancreaticoduodenectomy with conventional loop or Roux-en-Y reconstruction. Etiology of afferent loop obstruction includes:(1) entrapment, compression and kinking by postoperative adhesions;(2) internal herniation, volvulus and intussusception;(3) stenosis due to ulceration at the gastrojejunostomy site and radiation enteritis of the afferent loop;(4) cancer recurrence; and(5) enteroliths, bezoars and foreign bodies. Acute afferent loop obstruction is associated with complete obstruction of the afferent loop and represents a surgical emergency, whereas chronic afferent loop obstruction is associated with partial obstruction. Abdominal multiple detector computed tomography is the diagnostic study of choice. CT appearance of the obstructed afferent loop consists of a C-shaped, fluidfilled tubular mass located in the midline between the abdominal aorta and the superior mesenteric artery with valvulae conniventes projecting into the lumen. The cornerstone of treatment is surgery. Surgery includes:(1) adhesiolysis and reconstruction for benign causes; and(2) by-pass or excision and reconstruction for malignant causes. However, endoscopic enteral stenting, transhepatic percutaneous enteral stenting and direct percutaneous tube enterostomy have the principal role in management of malignant and radiation-induced obstruction. Nevertheless, considerable limitations exist as a former Roux-en-Y reconstruction limits endoscopic access to the afferent loop and percutaneous approaches for enteral stenting and tube enterostomy have only been reported in the literature as isolated cases.展开更多
Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal,immune and endocrine signaling pathways within the intestines,the peripheral and the central nervous system....Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal,immune and endocrine signaling pathways within the intestines,the peripheral and the central nervous system.In this article we review how the sensory nerve information from the healthy and the hypersensitive bowel is encoded and conveyed to the brain.The gut milieu is continuously monitored by intrinsic enteric afferents,and an extrinsic nervous network comprising vagal,pelvic and splanchnic afferents.The extrinsic afferents convey gut stimuli to second order neurons within the superficial spinal cord layers.These neurons cross the white commissure and ascend in the anterolateral quadrant and in the ipsilateral dorsal column of the dorsal horn to higher brain centers,mostly subserving regulatory functions.Within the supraspinal regions and the brainstem,pathways descend to modulate the sensory input.Because of this multiple level control,only a small proportion of gut signals actually reaches the level of consciousness to induce sensation or pain.In inflammatory bowel disease(IBD)and irritable bowel syndrome(IBS)patients,however,long-term neuroplastic changes have occurred in the brain-gut axis which results in chronic abdominal pain.This sensitization may be driven on the one hand by peripheral mechanisms within the intestinal wall which encompasses an interplay between immunocytes,enterochromaffin cells,resident macrophages,neurons and smooth muscles.On the other hand,neuronal synaptic changes along with increased neurotransmitter release in the spinal cord and brain leads to a state of central wind-up.Also life factors such as but not limited to inflammation and stress contribute to hypersensitivity.All together,the degree to which each of these mechanisms contribute to hypersensitivity in IBD and IBS might be diseaseand even patient-dependent.Mapping of sensitization throughout animal and human studies may significantly improve our understanding of sensitization in IBD and IBS.On the long run,this knowledge can be put forward in potential therapeutic targets for abdominal pain in these conditions.展开更多
AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to...AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）. METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.展开更多
Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the dis...Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-a and PPAR-c was assessed in the nodose ganglion(NG) and the nucleus of the solitary tract(NTS). Hypertension induced by drinking high fructose(HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-a and PPAR-c were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-a, the mitochondrial uncoupling protein 2(UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats.These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.展开更多
Propagated sensation along the meridian can occur when acupoints are stimulated by acupuncture or electrical impulses. In this study, participants with notable propagated sensation along the me- ridian were given elec...Propagated sensation along the meridian can occur when acupoints are stimulated by acupuncture or electrical impulses. In this study, participants with notable propagated sensation along the me- ridian were given electro-acupuncture at the Jianyu （LI15） acupoint of the large intestine meridian. When participants stated that the sensation reached the back of their hand, reguJar nervous system action discharge was examined using a physiological recording electrode placed on the superficial branch of the radial nerve. The topographical maps of brain-evoked potential in the primary cortical somatosensory area were also detected. When Guangming （GB37） acupoint in the lower limb and Hegu （LI4） acupoint in the upper limb were stimulated, subjects without propagated sensation along the meridian exhibited a high potential reaction in the corresponding area of the brain cortical somatosensory area. For subjects with a notable propagated sensation along the meridian, the re- action area was larger and extended into the face representative area. These electrophysiological measures directly prove the existence of propagated sensation along the meridian, and the periph- eral stimulated site is consistent with the corresponding primary cortical somatosensory area, which presents a high potential reaction.展开更多
AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mese...AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated dorsal root ganglia （DRG） and nodose ganglia （NG） neurons retrogradely labeled from the small intestine through injection of a fluorescent marker （DiI）. The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry. RESULTS： Ramp distension of the small intestine evok- ed biphasic increases in the afferent nerve activity, re- flecting the activation of low- and high-threshold fibers.HCN blocker CsCl （5 mmol/L） preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.展开更多
Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain an...Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.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
The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast...The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast exposure induces damage to the vestibular end organs in the inner ear.However,the underlying mechanisms remain to be elucidated.In this report,single vestibular afferent activity and the vestibuloocular reflex(VOR)were investigated before and after exposure to blast shock waves(~20 PSI)delivered into the left external ear canals of anesthetized rats.Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure.Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents.Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5e2Hz.Blast exposure,however,resulted in few changes in the VOR responses to sinusoidal head rotation and translation.To the best of our knowledge,this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model.These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.展开更多
Pancreatic cancer is an aggressive malignancy poten-tially curable with surgical intervention. Following pan-creaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immedi-ate...Pancreatic cancer is an aggressive malignancy poten-tially curable with surgical intervention. Following pan-creaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immedi-ate and delayed problems due to surgical complica-tions and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduode-nectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percu-taneous biliary decompression. During surgical explo-ration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical ap-proach for management of this complicated and diffi-cult problem.展开更多
Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of v...Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.展开更多
We report the case of an 84-year-old female who had a partial gastrectomy with Billroth-Ⅱ anastomosis 24 years ago for a benign peptic ulcer who now presented an acute pancreatitis secondary to an afferent loop syndr...We report the case of an 84-year-old female who had a partial gastrectomy with Billroth-Ⅱ anastomosis 24 years ago for a benign peptic ulcer who now presented an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was caused by a gallstone that migrated through a cholecystoenteric fistula. This is the first description in the literature of a biliary stone causing afferent loop syndrome.展开更多
Objective： The present study was designed to determine if reactive oxygen species （ROS） in the paraventricular nucleus （PVN） were involved in modulating cardiac sympathetic afferent reflex （CSAR） in anesthetize...Objective： The present study was designed to determine if reactive oxygen species （ROS） in the paraventricular nucleus （PVN） were involved in modulating cardiac sympathetic afferent reflex （CSAR） in anesthetized rats. Methods： Malondialdehyde （MDA）, the end product of lipid peroxidation, in the PVN, was determined by thiobarbituric acid （TBA） spectrometric method. Renal sympathetic nerve activity （RSNA） and arterial pressure were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the response of the RSNA evoked by epicardial application of bradykinin （BK, 0.4 9g）. Results： The MDA in the PVN was significantly increased after epicardial application of BK compared with control （2.0 ±0.3 vs 0.8 ±0.1 nmol/mg protein, P 〈 0.01）. Microinjection of a superoxide anion scavenger, tiron （20 nmol） into the PVN significantly inhibited the CSAR evoked by BK （12.3±1.9 vs4.2± 1.2%, P 〈0.01） and decreased MDA level （1.9±0.3 vs 0.6 ±0.1 nmol/mg protein, P 〈0.01） compared with control. Conclusion： The ROS in the PVN is involved in modulating the CSAR in rats.展开更多
基金Supported by Grant Baross (REG_DD_KFI_09,CAPSATAB,Hungary)
文摘AIM:To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H.pylori) positive chronic gastritis before and after eradication.METHODS:Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H.pylori positive chronic gastritis (n=18) before and after eradication.Tradi-tional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examina-tions were carried out.Immunohistochemistry for cap-saicin receptor (TRVP1),calcitonin gene-related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab VisionCo.,USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd.,UK).RESULTS:Eradication treatment was successful in 16 patients (89%).Seven patients (7/18,39%) re-mained with moderate complaints,meanwhile 11 pa-tients (11/28,61%) had no complaints.At histological evaluation,normal gastric mucosa was detected in 4 patients after eradication treatment (4/18,22%),and moderate chronic gastritis could be seen in 14 (14/18,78%) patients.Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls,89% (16/18,P < 0.001) in patients before and 72% (13/18,P < 0.03) after eradication.CGRP was positive in 40% (8/20) of controls,and in 100% (18/18,P < 0.001) of patients before and in 100% (18/18,P < 0.001) after eradication.The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy con-trols,and in 5.5% (3/18,P > 0.05) of patients before and in 0% of patients (0/18,P > 0.05) after H.pylori eradication.CONCLUSION:Distibution of TRVP1 and CGRP is altered during the development of H.pylori positive chronic gastritis.The immune-staining for TRVP1,CGRP and SP rwemained unchanged before and after H.py-lori eradication treatment.The capsaicin-sensitive affer-entation is an independent from the eradication treat-ment.The 6 wk time period might not be enough time for the restituion of chronic H.pylori positive chronic gastritis.The H.pylori infection might not represent the main pathological factor in the development of chronic
文摘Endoscopic ultrasound-guided gastroenterostomy(EUS-GE)has emerged as an effective and minimally invasive alternative for treating gastric outlet obstruction.Compared to traditional options,including duodenal stenting and surgical gastrojejunostomy,EUS-GE offers comparable technical and clinical success while providing longer-lasting patency,fewer adverse events,and lower reintervention rates.The technique has expanded beyond malignant obstruction to include benign etiologies and complex conditions such as afferent loop syndrome.EUSGE enables rapid recovery and early resumption of oral intake,which is crucial for oncologic patients.However,the procedure remains technically demanding,and optimal techniques,device selection,and management of complications are still under investigation.This mini-review summarizes current evidence,compares EUS-GE with alternative therapies,discusses patient selection and procedural aspects,and outlines key areas for future research.
基金supported by the National Research Foundation(NRF)of Korea(grant number:RS-2022-NR072217 to P.RL,RS-2021-NR059709,RS-2023-00264409,and RS-2024-00441103)funded by the Korean government(MSIT).
文摘Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
文摘Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system.
基金Supported by National Natural Science Foundation of China,No.81574071,No.81673883,and No.81873238Leading Talents of Traditional Chinese Medicine in Jiangsu Province(Second Batch),No.SLJ0225。
文摘Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acupuncture has a benign adjustment effect on gastrointestinal(GI) movement;however, the mechanism of this effect is unclear, especially in terms of neural mechanisms, and there are still many areas that require further exploration. This article reviews the recent data on the neural mechanism of acupuncture on GI movements. We summarize the neural mechanism of acupuncture on GI movement from four aspects: acupuncture signal transmission, the sympathetic and parasympathetic nervous system, the enteric nervous system, and the central nervous system.
基金Project (No. 30400163) supported by the National Natural Science Foundation of China
文摘Objective:The age-related change is important part of degenerative disc disease. However,no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods:22-month-old Sprague-Dawley(SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types II and X was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed. Results:There were less collagen type II expression and more collagen type X expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased,compared with that of the young control group(P<0.01) . Conclusion:Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types II and X,numbers and areas of afferent vascular buds,the ratio of the non-calcified to the calcified layers,and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.
基金supported by the National Key Research and Development Program of the Ministry of Science and Technology,China (2016YFC0105501,2019YFC1712104 and 2016YFF0202802)the National Natural Science Foundation of China (81974169, 81671085 and 61527815)。
文摘The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli.Acupuncture-like signals were elicited in PANs using three techniques:manual acupuncture(MAc),emulated acupuncture(EAc),and electro-acupuncture(EA)-like peripheral electrical stimulation(PES).The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz,respectively.The frequency of discharges in PANs was correlated with the frequency of PES.The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers.Therefore,EA in a dense-disperse mode(at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc.Frequencies of EA output>250 Hz appear to be obsolete for pain relief.
文摘Afferent loop obstruction is a purely mechanical complication that infrequently occurs following construction of a gastrojejunostomy. The operations most commonly associated with this complication are gastrectomy with Billroth Ⅱ or Roux-en-Y reconstruction, and pancreaticoduodenectomy with conventional loop or Roux-en-Y reconstruction. Etiology of afferent loop obstruction includes:(1) entrapment, compression and kinking by postoperative adhesions;(2) internal herniation, volvulus and intussusception;(3) stenosis due to ulceration at the gastrojejunostomy site and radiation enteritis of the afferent loop;(4) cancer recurrence; and(5) enteroliths, bezoars and foreign bodies. Acute afferent loop obstruction is associated with complete obstruction of the afferent loop and represents a surgical emergency, whereas chronic afferent loop obstruction is associated with partial obstruction. Abdominal multiple detector computed tomography is the diagnostic study of choice. CT appearance of the obstructed afferent loop consists of a C-shaped, fluidfilled tubular mass located in the midline between the abdominal aorta and the superior mesenteric artery with valvulae conniventes projecting into the lumen. The cornerstone of treatment is surgery. Surgery includes:(1) adhesiolysis and reconstruction for benign causes; and(2) by-pass or excision and reconstruction for malignant causes. However, endoscopic enteral stenting, transhepatic percutaneous enteral stenting and direct percutaneous tube enterostomy have the principal role in management of malignant and radiation-induced obstruction. Nevertheless, considerable limitations exist as a former Roux-en-Y reconstruction limits endoscopic access to the afferent loop and percutaneous approaches for enteral stenting and tube enterostomy have only been reported in the literature as isolated cases.
文摘Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal,immune and endocrine signaling pathways within the intestines,the peripheral and the central nervous system.In this article we review how the sensory nerve information from the healthy and the hypersensitive bowel is encoded and conveyed to the brain.The gut milieu is continuously monitored by intrinsic enteric afferents,and an extrinsic nervous network comprising vagal,pelvic and splanchnic afferents.The extrinsic afferents convey gut stimuli to second order neurons within the superficial spinal cord layers.These neurons cross the white commissure and ascend in the anterolateral quadrant and in the ipsilateral dorsal column of the dorsal horn to higher brain centers,mostly subserving regulatory functions.Within the supraspinal regions and the brainstem,pathways descend to modulate the sensory input.Because of this multiple level control,only a small proportion of gut signals actually reaches the level of consciousness to induce sensation or pain.In inflammatory bowel disease(IBD)and irritable bowel syndrome(IBS)patients,however,long-term neuroplastic changes have occurred in the brain-gut axis which results in chronic abdominal pain.This sensitization may be driven on the one hand by peripheral mechanisms within the intestinal wall which encompasses an interplay between immunocytes,enterochromaffin cells,resident macrophages,neurons and smooth muscles.On the other hand,neuronal synaptic changes along with increased neurotransmitter release in the spinal cord and brain leads to a state of central wind-up.Also life factors such as but not limited to inflammation and stress contribute to hypersensitivity.All together,the degree to which each of these mechanisms contribute to hypersensitivity in IBD and IBS might be diseaseand even patient-dependent.Mapping of sensitization throughout animal and human studies may significantly improve our understanding of sensitization in IBD and IBS.On the long run,this knowledge can be put forward in potential therapeutic targets for abdominal pain in these conditions.
基金Supported in part by the Kyoto Pharmaceutical University's "21st Century COE" program and the "Open Research" Program from the Ministry of Education, Science and Culture of Japan
文摘AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）. METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.
基金supported by the National Natural Science Foundation of China(81573431 and 81773731)
文摘Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-a and PPAR-c was assessed in the nodose ganglion(NG) and the nucleus of the solitary tract(NTS). Hypertension induced by drinking high fructose(HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-a and PPAR-c were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-a, the mitochondrial uncoupling protein 2(UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats.These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
基金supported by the General Project of the National Natural Science Foundation of China,No.30973720the Natural Science Foundation of Fujian Province in China,No.2011J01192Free Topics of Fujian Provincial Science & Technology Ministry in China,No.2012fjzyyk-6
文摘Propagated sensation along the meridian can occur when acupoints are stimulated by acupuncture or electrical impulses. In this study, participants with notable propagated sensation along the me- ridian were given electro-acupuncture at the Jianyu （LI15） acupoint of the large intestine meridian. When participants stated that the sensation reached the back of their hand, reguJar nervous system action discharge was examined using a physiological recording electrode placed on the superficial branch of the radial nerve. The topographical maps of brain-evoked potential in the primary cortical somatosensory area were also detected. When Guangming （GB37） acupoint in the lower limb and Hegu （LI4） acupoint in the upper limb were stimulated, subjects without propagated sensation along the meridian exhibited a high potential reaction in the corresponding area of the brain cortical somatosensory area. For subjects with a notable propagated sensation along the meridian, the re- action area was larger and extended into the face representative area. These electrophysiological measures directly prove the existence of propagated sensation along the meridian, and the periph- eral stimulated site is consistent with the corresponding primary cortical somatosensory area, which presents a high potential reaction.
基金Supported by Science and Technology Commission of Shanghai Municipality,No. 10ZR1417300Educational Commission of Shanghai Municipality,No. 10ZZ69
文摘AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated dorsal root ganglia （DRG） and nodose ganglia （NG） neurons retrogradely labeled from the small intestine through injection of a fluorescent marker （DiI）. The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry. RESULTS： Ramp distension of the small intestine evok- ed biphasic increases in the afferent nerve activity, re- flecting the activation of low- and high-threshold fibers.HCN blocker CsCl （5 mmol/L） preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.
基金supported by National Institutes of Health Grants R01NS89479,R01NS045594 and ROINS055860
文摘Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
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).
文摘The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast exposure induces damage to the vestibular end organs in the inner ear.However,the underlying mechanisms remain to be elucidated.In this report,single vestibular afferent activity and the vestibuloocular reflex(VOR)were investigated before and after exposure to blast shock waves(~20 PSI)delivered into the left external ear canals of anesthetized rats.Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure.Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents.Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5e2Hz.Blast exposure,however,resulted in few changes in the VOR responses to sinusoidal head rotation and translation.To the best of our knowledge,this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model.These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.
文摘Pancreatic cancer is an aggressive malignancy poten-tially curable with surgical intervention. Following pan-creaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immedi-ate and delayed problems due to surgical complica-tions and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduode-nectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percu-taneous biliary decompression. During surgical explo-ration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical ap-proach for management of this complicated and diffi-cult problem.
基金supported in part by the National Natural Science Foundation of China,No.81100939 and 81773713(to WH),No.81501610(to XC)the Research Project funded by Jiangsu Provincial Government of China,No.BRA2018223(to DGM)+2 种基金the Public Health Center at Jiangnan University of China,No.JUPH201808(to XSW)the Wuxi Commission of Public Health and Family Planning of China,No.MS201717(to XSW)the Project of Academic Development Program by Governments of Jiangsu Province and Nantong City of China(to DGM)
文摘Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.
文摘We report the case of an 84-year-old female who had a partial gastrectomy with Billroth-Ⅱ anastomosis 24 years ago for a benign peptic ulcer who now presented an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was caused by a gallstone that migrated through a cholecystoenteric fistula. This is the first description in the literature of a biliary stone causing afferent loop syndrome.
文摘Objective： The present study was designed to determine if reactive oxygen species （ROS） in the paraventricular nucleus （PVN） were involved in modulating cardiac sympathetic afferent reflex （CSAR） in anesthetized rats. Methods： Malondialdehyde （MDA）, the end product of lipid peroxidation, in the PVN, was determined by thiobarbituric acid （TBA） spectrometric method. Renal sympathetic nerve activity （RSNA） and arterial pressure were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the response of the RSNA evoked by epicardial application of bradykinin （BK, 0.4 9g）. Results： The MDA in the PVN was significantly increased after epicardial application of BK compared with control （2.0 ±0.3 vs 0.8 ±0.1 nmol/mg protein, P 〈 0.01）. Microinjection of a superoxide anion scavenger, tiron （20 nmol） into the PVN significantly inhibited the CSAR evoked by BK （12.3±1.9 vs4.2± 1.2%, P 〈0.01） and decreased MDA level （1.9±0.3 vs 0.6 ±0.1 nmol/mg protein, P 〈0.01） compared with control. Conclusion： The ROS in the PVN is involved in modulating the CSAR in rats.
