Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,c...BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.展开更多
BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bo...BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.展开更多
BACKGROUND Preoperative anxiety is a significant concern for patients,as it affects surgical outcomes,satisfaction,and pain perception.Although both anxiety and pain are common in surgical settings,their relationship ...BACKGROUND Preoperative anxiety is a significant concern for patients,as it affects surgical outcomes,satisfaction,and pain perception.Although both anxiety and pain are common in surgical settings,their relationship with personality traits has not been previously investigated in the Lebanese population.AIM To examine the prevalence of preoperative anxiety,pain perception,and personality traits among Lebanese surgical patients,and to assess the associations between these factors.METHODS A descriptive cross-sectional study was conducted between April 2024 and January 2025 across Lebanese hospitals.A total of 392 adult patients were recruited through convenience sampling.Data were collected using a questionnaire that included sociodemographic,clinical,and surgical variables,the Amsterdam Preoperative Anxiety and Information Scale for anxiety,the Visual Analog Scale and Numerical Pain Rating Scale for preoperative pain,and the Ten-Item Personality Inventory for personality traits.Ethical approval was obtained from the Institutional Review Boards of Makassed General Hospital and Hammoud University Medical Center.RESULTS Overall,25%of participants experienced preoperative anxiety,and 34.5%reported moderate pain.Personality assessment showed that the majority of participants had moderate extraversion(84.1%),moderate emotional stability(65.1%),high conscientiousness(61%),high agreeableness(54.1%),and moderate openness(49.2%).High conscientiousness was significantly associated with higher pain perception(P<0.05),while high emotional stability was associated with lower levels of anxiety(P<0.05).No significant association was found between preoperative anxiety and pain(P>0.05).CONCLUSION This study challenges the assumption that preoperative anxiety and pain are directly correlated and highlights the role of personality traits in shaping patient experience.These findings support the potential value of integrating psychological profiling into preoperative care and lay the groundwork for developing personalized interventions to improve patient-centered surgical outcomes.展开更多
Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the u...Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been consid...Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.展开更多
Pain is a subjective and unpleasant sensation that significantly impacts the daily lives of individuals.Chronic pain represents one of the most challenging public health issues,and ensuring effective pain management i...Pain is a subjective and unpleasant sensation that significantly impacts the daily lives of individuals.Chronic pain represents one of the most challenging public health issues,and ensuring effective pain management is a fundamental right of individuals and a sacred duty of healthcare providers.Cannabis,one of the earliest recognized medicinal plants,contains cannabinoids,which are non-opioid substances that modulate nociceptive responses.Electroacupuncture(EA),characterized by its low-risk and well-tolerated nature,is pivotal in pain management.The endocannabinoid system consists of endocannabinoids,cannabinoid receptors,and enzymes involved in endocannabinoid synthesis,degradation,and transport.Recently,the role of the endocannabinoid system in pain development and EA analgesia has attracted considerable research attention.Studies have highlighted the role of the endocannabinoid system in various types of pain,including inflammatory pain,neuropathic pain,and cancer-related pain,as well as in EA analgesia.This study aims to review the mechanisms of endocannabinoid system involvement in pain modulation and EA analgesia to provide insights to inform clinical approaches to pain management.展开更多
Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,...Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,we used resting-state functional magnetic resonance imaging(rs-fMRI)to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve(CION)and then treating these animals with EA.Methods:Forty male C57BL/6J mice were divided into 4 groups:control,CION model,EA,and sham acupuncture(without needle insertion).EA was performed on the acupoints Baihui(GV20)and Zusanli(ST36)for 20 min,once a day for 10 consecutive days.The mechanical withdrawal threshold was tested3 days after the surgery and every 3 days after the intervention.The depressive behavior was evaluated with the tail suspension test,open-field test,elevated plus maze(EPM),sucrose preference test,and marble burying test.The rs-fMRI was used to detect the cerebral changes of the functional connectivity(FC)in the mice following EA treatment.Results:Compared with the CION group,the mechanical withdrawal threshold increased in the EA group at the end of the intervention(P<0.05);the immobility time in tail suspension test decreased(P<0.05);and the times of the open arm entry and the open arm time in the EPM increased(both P<0.001).There was no difference in the sucrose preference or marble burying tests(both P>0.05).The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values,while these indicators were elevated in brain regions including the amygdala,hippocampus and cerebral cortex in the CION model for comorbid pain and depression.Selecting the amygdala as the seed region,we found that the FC was higher in the CION group than in the control group.Meanwhile,EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen,thalamus,and parts of the cerebral cortex.Conclusion:EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions,thus exerting analgesic and antidepressant effects.Please cite this article as:Yin X,Zeng XL,Lin JJ,Xu WQ,Cui KY,Guo XT,Li W,Xu SF.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression:A restingstate functional magnetic resonance imaging study.展开更多
BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few stu...BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.展开更多
Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the imp...Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasmaβ-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA andβ-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasmaβ-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P<0.00001],24 hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P<0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasmaβ-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.展开更多
Phantom limb pain(PLP)is not only a physical pain experience but also poses a significant challenge to mental health and quality of life.Currently,the mechanism of PLP treatment is still unclear,and there are many met...Phantom limb pain(PLP)is not only a physical pain experience but also poses a significant challenge to mental health and quality of life.Currently,the mechanism of PLP treatment is still unclear,and there are many methods with varying effects.This article starts with the application research of extended reality technology in PLP treatment,through describing the application of its branch technologies(virtual reality,augmented reality,and mixed reality technology),to lay the foundation for subsequent research,in the hope of finding advanced and effective treatment methods,and providing a basis for future product transformation.展开更多
BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pat...BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pathophysiological factor in functional gastrointestinal disorders,may be influenced by body mass index(BMI).AIM To evaluate the impact of BMI on gastric motility parameters in children with functional abdominal pain disorders(FAPDs).METHODS We assessed gastric motility in 176 children with FAPDs(61.4%females,mean age 7.94 years,SD 1.96 years)and 63 healthy controls(57.1%females,mean age 9.17 years,SD 1.90 years)at the Gastroenterology Research Laboratory,University of Kelaniya,Sri Lanka.FAPDs were diagnosed and subtyped using the Rome IV criteria:Functional abdominal pain 97 patients;irritable bowel syndrome 39 patients,functional dyspepsia(FD)25 patients;and abdominal migraine 15 patients.Gastric motility was measured using a validated ultrasound method.Weight and height were measured using sensitive standard scales.RESULTS The BMIs of children with FAPDs and controls were 15.04 and 15.46 kg/m^(2),respectively(P=0.33).Fasting antral area(FAA)and antral area at 1 min(AA1)and 15 min(AA15)were significantly greater in patients with FAPD with a higher BMI(2.71 cm^(2),12.57 cm^(2),and 7.19 cm^(2),respectively)compared with those with a lower BMI(2.12 cm^(2),10.68 cm^(2),and 6.13 cm^(2),respectively)(P<0.01).BMI positively correlated with FAA and AA15(r=0.18 and r=0.19,respectively)(P<0.01)in those with FAPDs.In controls,only AA1 was greater in the higher BMI group(12.51 cm^(2)vs 9.93 cm^(2))and had a positive correlation(r=0.33)(P≤0.01).Subgroup analysis revealed that in patients with FD,BMI negatively correlated with gastric emptying rate(GER)(r=-0.59)and antral motility index(MI)(r=-0.49),while in functional abdominal pain,MI positively correlated(r=0.25)with BMI(P≤0.01).CONCLUSION In children with FAPDs,higher BMI was associated with increased gastric antral distention during fasting and postprandial periods(as indicated by FAA,AA1,and AA15)but not with contractility and transit(MI,GER).However,in the FD subgroup,high BMI correlated with reduced GER and MI.This indicates the possible role of BMI in gastric hypomotility and the pathophysiology of FD.These findings underscore the importance of lifestyle and dietary interventions aimed at optimizing BMI in the management of FAPDs,particularly FD.展开更多
Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain tha...Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain that significantly affects the quality of life of afflicted women.The present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.展开更多
In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD patho...In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.展开更多
Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ...Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poo...In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poor management of postcesarean pain is associated with decreased maternal care for the baby,longer hospitalization,and higher risk of developing postpartum depression.Esketamine is a more potent S-enantiomer of ketamine which has shown promising analgesic and antidepressant properties for managing post-cesarean pain and depression in clinical studies.However,due to its potential adverse effects on the neurological and hemodynamic status of patients,it is recommended that its usage in low doses should be limited to cesarean candidates experiencing unbearable pain.Before any recommendation for routine perioperative use of esketamine,more standardized clinical trials are needed to strengthen our existing knowledge of its effectiveness in reducing postpartum pain and depression.展开更多
In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epice...In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.展开更多
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.
文摘BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.
文摘BACKGROUND Preoperative anxiety is a significant concern for patients,as it affects surgical outcomes,satisfaction,and pain perception.Although both anxiety and pain are common in surgical settings,their relationship with personality traits has not been previously investigated in the Lebanese population.AIM To examine the prevalence of preoperative anxiety,pain perception,and personality traits among Lebanese surgical patients,and to assess the associations between these factors.METHODS A descriptive cross-sectional study was conducted between April 2024 and January 2025 across Lebanese hospitals.A total of 392 adult patients were recruited through convenience sampling.Data were collected using a questionnaire that included sociodemographic,clinical,and surgical variables,the Amsterdam Preoperative Anxiety and Information Scale for anxiety,the Visual Analog Scale and Numerical Pain Rating Scale for preoperative pain,and the Ten-Item Personality Inventory for personality traits.Ethical approval was obtained from the Institutional Review Boards of Makassed General Hospital and Hammoud University Medical Center.RESULTS Overall,25%of participants experienced preoperative anxiety,and 34.5%reported moderate pain.Personality assessment showed that the majority of participants had moderate extraversion(84.1%),moderate emotional stability(65.1%),high conscientiousness(61%),high agreeableness(54.1%),and moderate openness(49.2%).High conscientiousness was significantly associated with higher pain perception(P<0.05),while high emotional stability was associated with lower levels of anxiety(P<0.05).No significant association was found between preoperative anxiety and pain(P>0.05).CONCLUSION This study challenges the assumption that preoperative anxiety and pain are directly correlated and highlights the role of personality traits in shaping patient experience.These findings support the potential value of integrating psychological profiling into preoperative care and lay the groundwork for developing personalized interventions to improve patient-centered surgical outcomes.
文摘Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金National Nature Science Foundation of China 82471000(to K.J.)National Nature Science Foundation of China 82170978(to K.J.)+1 种基金National Nature Science Foundation of China 82325012(to L.N.N.)National Key Research and Development Program 2023YFC2509100(to K.J.)。
文摘Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.
基金supported by the Key Program of the National Natural Science Foundation of China(82130122)the National Natural Science Foundation of China(81973949).
文摘Pain is a subjective and unpleasant sensation that significantly impacts the daily lives of individuals.Chronic pain represents one of the most challenging public health issues,and ensuring effective pain management is a fundamental right of individuals and a sacred duty of healthcare providers.Cannabis,one of the earliest recognized medicinal plants,contains cannabinoids,which are non-opioid substances that modulate nociceptive responses.Electroacupuncture(EA),characterized by its low-risk and well-tolerated nature,is pivotal in pain management.The endocannabinoid system consists of endocannabinoids,cannabinoid receptors,and enzymes involved in endocannabinoid synthesis,degradation,and transport.Recently,the role of the endocannabinoid system in pain development and EA analgesia has attracted considerable research attention.Studies have highlighted the role of the endocannabinoid system in various types of pain,including inflammatory pain,neuropathic pain,and cancer-related pain,as well as in EA analgesia.This study aims to review the mechanisms of endocannabinoid system involvement in pain modulation and EA analgesia to provide insights to inform clinical approaches to pain management.
基金supported by National Natural Science Foundation of China(No.82104986 and 82274643)Shanghai“Rising Stars of Medical Talents”Youth Development Program(No.SHWSRS[2023]_062)from Shanghai Municipal Health Commission。
文摘Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,we used resting-state functional magnetic resonance imaging(rs-fMRI)to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve(CION)and then treating these animals with EA.Methods:Forty male C57BL/6J mice were divided into 4 groups:control,CION model,EA,and sham acupuncture(without needle insertion).EA was performed on the acupoints Baihui(GV20)and Zusanli(ST36)for 20 min,once a day for 10 consecutive days.The mechanical withdrawal threshold was tested3 days after the surgery and every 3 days after the intervention.The depressive behavior was evaluated with the tail suspension test,open-field test,elevated plus maze(EPM),sucrose preference test,and marble burying test.The rs-fMRI was used to detect the cerebral changes of the functional connectivity(FC)in the mice following EA treatment.Results:Compared with the CION group,the mechanical withdrawal threshold increased in the EA group at the end of the intervention(P<0.05);the immobility time in tail suspension test decreased(P<0.05);and the times of the open arm entry and the open arm time in the EPM increased(both P<0.001).There was no difference in the sucrose preference or marble burying tests(both P>0.05).The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values,while these indicators were elevated in brain regions including the amygdala,hippocampus and cerebral cortex in the CION model for comorbid pain and depression.Selecting the amygdala as the seed region,we found that the FC was higher in the CION group than in the control group.Meanwhile,EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen,thalamus,and parts of the cerebral cortex.Conclusion:EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions,thus exerting analgesic and antidepressant effects.Please cite this article as:Yin X,Zeng XL,Lin JJ,Xu WQ,Cui KY,Guo XT,Li W,Xu SF.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression:A restingstate functional magnetic resonance imaging study.
文摘BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.
基金Supported by Beijing Natural Science Foundation(7232130)Fundamental Research Funds for the Central Universities(2024-JYB-JBZD-024)CZ015-High Level Traditional Chinese Medicine Hospital SM Project(DZMG-LJRC0006)。
文摘Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasmaβ-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA andβ-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasmaβ-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P<0.00001],24 hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P<0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasmaβ-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.
文摘Phantom limb pain(PLP)is not only a physical pain experience but also poses a significant challenge to mental health and quality of life.Currently,the mechanism of PLP treatment is still unclear,and there are many methods with varying effects.This article starts with the application research of extended reality technology in PLP treatment,through describing the application of its branch technologies(virtual reality,augmented reality,and mixed reality technology),to lay the foundation for subsequent research,in the hope of finding advanced and effective treatment methods,and providing a basis for future product transformation.
基金Supported by The University of Kelaniya,Sri Lanka,Research Council Grant No.G23.
文摘BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pathophysiological factor in functional gastrointestinal disorders,may be influenced by body mass index(BMI).AIM To evaluate the impact of BMI on gastric motility parameters in children with functional abdominal pain disorders(FAPDs).METHODS We assessed gastric motility in 176 children with FAPDs(61.4%females,mean age 7.94 years,SD 1.96 years)and 63 healthy controls(57.1%females,mean age 9.17 years,SD 1.90 years)at the Gastroenterology Research Laboratory,University of Kelaniya,Sri Lanka.FAPDs were diagnosed and subtyped using the Rome IV criteria:Functional abdominal pain 97 patients;irritable bowel syndrome 39 patients,functional dyspepsia(FD)25 patients;and abdominal migraine 15 patients.Gastric motility was measured using a validated ultrasound method.Weight and height were measured using sensitive standard scales.RESULTS The BMIs of children with FAPDs and controls were 15.04 and 15.46 kg/m^(2),respectively(P=0.33).Fasting antral area(FAA)and antral area at 1 min(AA1)and 15 min(AA15)were significantly greater in patients with FAPD with a higher BMI(2.71 cm^(2),12.57 cm^(2),and 7.19 cm^(2),respectively)compared with those with a lower BMI(2.12 cm^(2),10.68 cm^(2),and 6.13 cm^(2),respectively)(P<0.01).BMI positively correlated with FAA and AA15(r=0.18 and r=0.19,respectively)(P<0.01)in those with FAPDs.In controls,only AA1 was greater in the higher BMI group(12.51 cm^(2)vs 9.93 cm^(2))and had a positive correlation(r=0.33)(P≤0.01).Subgroup analysis revealed that in patients with FD,BMI negatively correlated with gastric emptying rate(GER)(r=-0.59)and antral motility index(MI)(r=-0.49),while in functional abdominal pain,MI positively correlated(r=0.25)with BMI(P≤0.01).CONCLUSION In children with FAPDs,higher BMI was associated with increased gastric antral distention during fasting and postprandial periods(as indicated by FAA,AA1,and AA15)but not with contractility and transit(MI,GER).However,in the FD subgroup,high BMI correlated with reduced GER and MI.This indicates the possible role of BMI in gastric hypomotility and the pathophysiology of FD.These findings underscore the importance of lifestyle and dietary interventions aimed at optimizing BMI in the management of FAPDs,particularly FD.
文摘Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain that significantly affects the quality of life of afflicted women.The present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.
文摘In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.
基金supported by the National Natural Science Foundation of China,Nos.82001178(to LW),81901129(to LH),82001175(to FX)Shanghai Sailing Program,No.20YF1439200(to LW)+1 种基金the Natural Science Foundation of Shanghai,China,No.23ZR1450800(to LH)and the Fundamental Research Funds for the Central Universities,No.YG2023LC15(to ZX)。
文摘Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
文摘In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poor management of postcesarean pain is associated with decreased maternal care for the baby,longer hospitalization,and higher risk of developing postpartum depression.Esketamine is a more potent S-enantiomer of ketamine which has shown promising analgesic and antidepressant properties for managing post-cesarean pain and depression in clinical studies.However,due to its potential adverse effects on the neurological and hemodynamic status of patients,it is recommended that its usage in low doses should be limited to cesarean candidates experiencing unbearable pain.Before any recommendation for routine perioperative use of esketamine,more standardized clinical trials are needed to strengthen our existing knowledge of its effectiveness in reducing postpartum pain and depression.
基金supported by COBRE(P30GM149367)the Puerto Rico Science&Technology Trust(2022-00125)+1 种基金MBRS-RISE Program(R25 GM061838)SC1GM144032 program(all to JDM)。
文摘In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.
