BACKGROUND:Central sensitization,a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation,is an important mechanism underlying hyperalge...BACKGROUND:Central sensitization,a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation,is an important mechanism underlying hyperalgesia and neuropathic pain.Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood.OBJECTIVE:To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Institute of Orthopedics,Second Hospital,Lanzhou University,China from September 2007 to August 2008.MATERIALS:Methionine sulfoximine(MSO,0.1 mmol/L),glutamine(0.25 mmol/L),and formalin were used for this study.METHODS:A total of 43 male,Sprague Dawley rats,aged 4 months,were randomly assigned to a sham operation group(n=6)and a model group(n=37).Rats in the model group received intrathecal infusion in the spinal cord.7 days later,37 model rats were randomly divided into PBS,MSO,glutamine,MSO+glutamine and formalin subcutaneous injection alone groups.The PBS,MSO,glutamine,MSO+glutamine groups were respectively intrathecally injected with PBS,MSO,glutamine,MSO+glutamine(50μL each),and then infused with 10μL of saline.Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord.At 15 minutes after intrathecal injection,a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5%formalin(50μL)in the left hindpaw.MAIN OUTCOME MEASURES:Changes in spontaneous nociceptive behavior(licking/biting or flinching)were observed following formalin injection into the rat hindpaw.RESULTS:Compared with the PBS group,duration of licking/biting was significantly shortened,and flinching frequency was significantly diminished in the MSO group(P〈0.05).Compared with the MSO group,duration of licking/biting was significantly prolonged,and flinching frequency was significantly increased in the MSO+glutamine group(P〈0.05).There was no significant difference in inflammatory pain behaviors among the sham operation,PBS,glutamine,MSO+glutamine,and formalin subcutaneous injection alone groups(P〉0.05).CONCLUSION:The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.展开更多
Central sensitization has been associated with chronic pain in whiplash patients.Methods:Consecutive whiplash patients were assessed at 3 months post-whiplash injury with the brachial plexus provocation test(BPPT)as a...Central sensitization has been associated with chronic pain in whiplash patients.Methods:Consecutive whiplash patients were assessed at 3 months post-whiplash injury with the brachial plexus provocation test(BPPT)as a sign of central sensitization.Self-reported recovery was assessed by the response to the question ‘Do you feel you have recovered fully from your accident injuries?'Results:Sixty-nine subjects(32 males,37 females,age 37.5±13.0 years(mean±SD),range 18-71)were included.Of these,34 reported a lack of recovery,and 35 reported recovery at 3 months post-injury.The mean BPPT elbow extension(from 180°)was 41.5±23.0°,and the mean VAS score for the BPPT was 2.2 ± 1.2(out of 10).Those who reported recovery had a mean BPPT elbow extension angle of 25.1±15.8 while those who did not report recovery had a mean BPPT angle of 58.4 ± 15.9(P＜0.05).The visual analogue scale(VAS)score for recovered subjects was 1.8 ± 1.1 and 2.7 ± 1.1(P＜0.05)for non-recovered.There was a moderate correlation between self-reported recovery and BPPT elbow extension angle(-0.44)and a lower correlation between self-reported recovery and VAS score(-0.30).Conclusion:Self-reported recovery correlates well with a lower likelihood of signs of central sensitization.Copyright(c)2012,Shanghai University of Sport.Production and hosting by Elsevier B.V.All rights reserved.展开更多
Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtyp...Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtype-I （TNFR1） and TNFR2 in acute and chronic itch in mice. Compared to wild-type （WT） mice, TNFRl-knockout （TNFR1-KO） and TNFR1/R2 double-KO （DKO）, but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine （CQ）. Application of the TNF-synthesis inhibitor thalidomide and the TNF-at antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia （DRG） and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etaner- cept and in TNFR1/R2 DKO mice. Dry skin induced TNF- expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-c^-fNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be benefi- cial for chronic itch treatment.展开更多
Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects w...Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects women and can result in significant psychological distress due to repeated dismissal of symptoms.Despite low serum alkaline phosphatase(ALP)being a key biochemical clue to HPP,it is frequently overlooked in standard diagnostic evaluations.Consequen-tly,many patients endure years of ineffective treatment,invalidation,and worse-ning psychiatric outcomes.This editorial emphasizes the need for greater clinical vigilance in distinguishing HPP from fibromyalgia,particularly when features such as chronic pain,premature tooth loss,and persistently low ALP are present.Gender biases in pain diagnosis further compound this problem,leading to gr-eater misdiagnosis rates among women and contributing to the erosion of trust in medical care.The psychiatric consequences of diagnostic delays are substantial,with affected individuals experiencing elevated rates of depression,anxiety,and emotional distress.Greater recognition of low ALP as a meaningful diagnostic clue may enhance diagnostic accuracy,improve patient outcomes,and reduce the psychological toll of misdiagnosis.展开更多
BACKGROUND Although total hip arthroplasty(THA)is an established intervention for advanced hip disorders,not all patients achieve the anticipated functional improvements.AIM To investigate the impact of various preope...BACKGROUND Although total hip arthroplasty(THA)is an established intervention for advanced hip disorders,not all patients achieve the anticipated functional improvements.AIM To investigate the impact of various preoperative factors on clinical outcomes after THA.METHODS Data of 411 patients who underwent unilateral THA were retrospectively analyzed.The associations between preoperative factors,such as age,body mass index,pain severity,functional impairment,psychological status,neuropathic pain,and central sensitization,and clinical outcomes assessed six months postoperatively using the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)and modified Harris Hip Score were evaluated.RESULTS Our results indicated that age and the WOMAC,Center for Epidemiologic Studies Depression Scale,and Central Sensitization Index(CSI)scores significantly predicted the modified Harris Hip Score outcomes,whereas age and preoperative WOMAC,EuroQol 5 dimensions,Center for Epidemiologic Studies Depression Scale,CSI,and Pain Detect Questionnaire scores were significant predictors of WOMAC outcomes.Age,WOMAC,and CSI were consistently significant factors.There were no significant differences in the operative time or blood loss across the outcome categories.CONCLUSION Our findings highlight the importance of preoperative assessment of central sensitization and psychological parameters.Patient-specific preoperative characteristics may play a greater role than intraoperative factors in determining recovery outcomes after THA.展开更多
Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key...Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis.This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels:(1)Peripheral Sensitization:CCL2/CCR2 modulates TRPV1,Nav1.8,and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain.(2)Spinal Cord Central Sensitization:CCL2/CCR2 contributes to NMDAR-dependent plasticity,glial activation,GABAergic disinhibition,and opioid receptor desensitization.(3)Supraspinal Central Networks:CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions,including the ACC,CeA,NAc,and hippocampus,and it also increases pain sensitization through the descending facilitation system.Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed,highlighting novel avenues for chronic pain management.展开更多
Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain inclu...Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a...Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.展开更多
Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidenc...Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidence. In this study, double-labeling immunofluorescence techniques showed that after rats were intrathecally injected with PBS and plantarly injected with formalin, glial fibrillary acidic protein （GFAP） and glutamine synthesase （GS） expression were increased and GFAP/GS coexpression was changed to include layers III and IV. After intrathecal injection of methionine sulfoximine, a GS specific inhibitor, the formalin-induced change in expression and coexpression of GFAP and GS in spinal cord dorsal horns was inhibited. The morphology, distribution and quantity of astrocytes recovered to normal levels. An intrathecal glutamine injection reversed the inhibitory effect of methionine sulfoximine. Astrocytes showed significant activation and distribution extended to layers V and VI. The present study provides morphological evidence that the astroglial glutamateglutamine cycle is involved in the process of formalin-induced spinal cord central sensitization.展开更多
While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,w...While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,which major classes refer to inflammatory,neuropathic,and idiopathic pain.It is frequent,with up to a third of the population that may suffer at one point from chronic pain.It is often associated with other pathologies,including sleep disorders,anxiety,depression,and is still difficult to treat.It thus represents a significant burden in terms of health and societal impact(Tracey et al.,2019).The mechanisms of chronic pain involve multiple diverse pathways in both the peripheral and central nervous systems(CNS),reflecting its multifaceted biology.Indeed,research over the past decades has established that central sensitization(enhancement in the function of neurons and circuits in central nociceptive pathways),in particular within the dorsal horn,the first central relay of nociceptive inputs plays a key role in the chronicity of pain(Latremoliere and Woolf,2009).展开更多
Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain s...Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kgbw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF_(2α))level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF_(2α)level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF_(2α)levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF_(2α)level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.展开更多
Abdominal pain is the most common symptom of chronic pancreatitis(CP)and is often debilitating for patients and very difficult to treat.To date,there exists no cure for the disease.Treatment strategies focus on sympto...Abdominal pain is the most common symptom of chronic pancreatitis(CP)and is often debilitating for patients and very difficult to treat.To date,there exists no cure for the disease.Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events.Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain.The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders,exocrine pancreatic insufficiency,mineral bone disease,frailty,and malnutrition,are in its early stages.Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain,as well as to improve pain management.Despite the array of tools available,many therapeutic options for the management of CP pain provide incomplete relief.There still remains much to discover about the neural regulation of pancreas-related pain.In this review,we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain.These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management,and identification of potential future therapies.展开更多
Objective To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome(IBS)visceral hyperalgesia model rats and its regulatory effect on P2X3 receptors in the spinal cord,anterior cingutate cortex...Objective To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome(IBS)visceral hyperalgesia model rats and its regulatory effect on P2X3 receptors in the spinal cord,anterior cingutate cortex(ACC)and thalamic ventral posterolateral nucleus(VPL).Methods Thirty 8-day-old newborn rats were randomly divided into a normal group(n=6)and a modeling group(n=24)according to the completely random number table method.Rats in the normal group were bred routinely,and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention(CRD)in stimulation method.Rats successfully modelled were re-divided into a model group,a mild moxibustion group,a P2X3 receptor antagonist group,and a normal saline group according to the completely random number table method with 6 rats in each group.Rats in each group received corresponding interventions from the 37-day old,once a day for 7 consecutive days.Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord,ACC and VPL of rats.Results Under different intensities of CRD stimulation,the abdominal withdrawal reflex(AWR)scores of the model group were significantly increased versus the normal group(all P<0.05);the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group(all P<0.01).The P2X3 protein expressions in rat spinal cord,ACC and VPL tissues of the model group were significantly increased versus the normal group(all P<0.01);the P2X3 protein expressions in rat spinal cord,ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group(all P<0.01).Conclusion Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord,ACC,and VPL tissues of IBS visceral hyperalgesia model rats,which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.展开更多
基金the National Science Foundation of China,No.30800333
文摘BACKGROUND:Central sensitization,a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation,is an important mechanism underlying hyperalgesia and neuropathic pain.Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood.OBJECTIVE:To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Institute of Orthopedics,Second Hospital,Lanzhou University,China from September 2007 to August 2008.MATERIALS:Methionine sulfoximine(MSO,0.1 mmol/L),glutamine(0.25 mmol/L),and formalin were used for this study.METHODS:A total of 43 male,Sprague Dawley rats,aged 4 months,were randomly assigned to a sham operation group(n=6)and a model group(n=37).Rats in the model group received intrathecal infusion in the spinal cord.7 days later,37 model rats were randomly divided into PBS,MSO,glutamine,MSO+glutamine and formalin subcutaneous injection alone groups.The PBS,MSO,glutamine,MSO+glutamine groups were respectively intrathecally injected with PBS,MSO,glutamine,MSO+glutamine(50μL each),and then infused with 10μL of saline.Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord.At 15 minutes after intrathecal injection,a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5%formalin(50μL)in the left hindpaw.MAIN OUTCOME MEASURES:Changes in spontaneous nociceptive behavior(licking/biting or flinching)were observed following formalin injection into the rat hindpaw.RESULTS:Compared with the PBS group,duration of licking/biting was significantly shortened,and flinching frequency was significantly diminished in the MSO group(P〈0.05).Compared with the MSO group,duration of licking/biting was significantly prolonged,and flinching frequency was significantly increased in the MSO+glutamine group(P〈0.05).There was no significant difference in inflammatory pain behaviors among the sham operation,PBS,glutamine,MSO+glutamine,and formalin subcutaneous injection alone groups(P〉0.05).CONCLUSION:The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.
文摘Central sensitization has been associated with chronic pain in whiplash patients.Methods:Consecutive whiplash patients were assessed at 3 months post-whiplash injury with the brachial plexus provocation test(BPPT)as a sign of central sensitization.Self-reported recovery was assessed by the response to the question ‘Do you feel you have recovered fully from your accident injuries?'Results:Sixty-nine subjects(32 males,37 females,age 37.5±13.0 years(mean±SD),range 18-71)were included.Of these,34 reported a lack of recovery,and 35 reported recovery at 3 months post-injury.The mean BPPT elbow extension(from 180°)was 41.5±23.0°,and the mean VAS score for the BPPT was 2.2 ± 1.2(out of 10).Those who reported recovery had a mean BPPT elbow extension angle of 25.1±15.8 while those who did not report recovery had a mean BPPT angle of 58.4 ± 15.9(P＜0.05).The visual analogue scale(VAS)score for recovered subjects was 1.8 ± 1.1 and 2.7 ± 1.1(P＜0.05)for non-recovered.There was a moderate correlation between self-reported recovery and BPPT elbow extension angle(-0.44)and a lower correlation between self-reported recovery and VAS score(-0.30).Conclusion:Self-reported recovery correlates well with a lower likelihood of signs of central sensitization.Copyright(c)2012,Shanghai University of Sport.Production and hosting by Elsevier B.V.All rights reserved.
基金supported by grants from the National Natural Science Foundation of China(31371179 and 81300968)the Natural Science Foundation of Jiangsu Province,China(BK20140372)+2 种基金the Scientific Funding from Jiangsu Province,China(2015-JY-029)the Second Affiliated Hospital of Soochow University Preponderant Clinic Discipline Group Project Funding(XKQ2015007)a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,Jiangsu Province,China
文摘Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtype-I （TNFR1） and TNFR2 in acute and chronic itch in mice. Compared to wild-type （WT） mice, TNFRl-knockout （TNFR1-KO） and TNFR1/R2 double-KO （DKO）, but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine （CQ）. Application of the TNF-synthesis inhibitor thalidomide and the TNF-at antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia （DRG） and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etaner- cept and in TNFR1/R2 DKO mice. Dry skin induced TNF- expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-c^-fNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be benefi- cial for chronic itch treatment.
文摘Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects women and can result in significant psychological distress due to repeated dismissal of symptoms.Despite low serum alkaline phosphatase(ALP)being a key biochemical clue to HPP,it is frequently overlooked in standard diagnostic evaluations.Consequen-tly,many patients endure years of ineffective treatment,invalidation,and worse-ning psychiatric outcomes.This editorial emphasizes the need for greater clinical vigilance in distinguishing HPP from fibromyalgia,particularly when features such as chronic pain,premature tooth loss,and persistently low ALP are present.Gender biases in pain diagnosis further compound this problem,leading to gr-eater misdiagnosis rates among women and contributing to the erosion of trust in medical care.The psychiatric consequences of diagnostic delays are substantial,with affected individuals experiencing elevated rates of depression,anxiety,and emotional distress.Greater recognition of low ALP as a meaningful diagnostic clue may enhance diagnostic accuracy,improve patient outcomes,and reduce the psychological toll of misdiagnosis.
文摘BACKGROUND Although total hip arthroplasty(THA)is an established intervention for advanced hip disorders,not all patients achieve the anticipated functional improvements.AIM To investigate the impact of various preoperative factors on clinical outcomes after THA.METHODS Data of 411 patients who underwent unilateral THA were retrospectively analyzed.The associations between preoperative factors,such as age,body mass index,pain severity,functional impairment,psychological status,neuropathic pain,and central sensitization,and clinical outcomes assessed six months postoperatively using the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)and modified Harris Hip Score were evaluated.RESULTS Our results indicated that age and the WOMAC,Center for Epidemiologic Studies Depression Scale,and Central Sensitization Index(CSI)scores significantly predicted the modified Harris Hip Score outcomes,whereas age and preoperative WOMAC,EuroQol 5 dimensions,Center for Epidemiologic Studies Depression Scale,CSI,and Pain Detect Questionnaire scores were significant predictors of WOMAC outcomes.Age,WOMAC,and CSI were consistently significant factors.There were no significant differences in the operative time or blood loss across the outcome categories.CONCLUSION Our findings highlight the importance of preoperative assessment of central sensitization and psychological parameters.Patient-specific preoperative characteristics may play a greater role than intraoperative factors in determining recovery outcomes after THA.
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203205 and 2021ZD0203104)the National Natural Science Foundation of China(82371225,82171212,82571386,82330036 and 82221001)+2 种基金National Key Research and Development Program of China(2024YFC2510102)the Excellent Youth Science Foundation of Shaanxi Province(2025JC-JCQN-103)Shaanxi Province Sanqin Talent Program.
文摘Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis.This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels:(1)Peripheral Sensitization:CCL2/CCR2 modulates TRPV1,Nav1.8,and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain.(2)Spinal Cord Central Sensitization:CCL2/CCR2 contributes to NMDAR-dependent plasticity,glial activation,GABAergic disinhibition,and opioid receptor desensitization.(3)Supraspinal Central Networks:CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions,including the ACC,CeA,NAc,and hippocampus,and it also increases pain sensitization through the descending facilitation system.Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed,highlighting novel avenues for chronic pain management.
文摘Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
文摘Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.
基金the National Natural Science Foundation of China, No. 30800333the Fundamental Research Funds for the Central Universities, No. lzujbky-2010-148
文摘Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidence. In this study, double-labeling immunofluorescence techniques showed that after rats were intrathecally injected with PBS and plantarly injected with formalin, glial fibrillary acidic protein （GFAP） and glutamine synthesase （GS） expression were increased and GFAP/GS coexpression was changed to include layers III and IV. After intrathecal injection of methionine sulfoximine, a GS specific inhibitor, the formalin-induced change in expression and coexpression of GFAP and GS in spinal cord dorsal horns was inhibited. The morphology, distribution and quantity of astrocytes recovered to normal levels. An intrathecal glutamine injection reversed the inhibitory effect of methionine sulfoximine. Astrocytes showed significant activation and distribution extended to layers V and VI. The present study provides morphological evidence that the astroglial glutamateglutamine cycle is involved in the process of formalin-induced spinal cord central sensitization.
基金Institut National de la Santéet de la Recherche Médicale(Inserm)UniversitéClermont Auvergne(France)+2 种基金CHU Clermont-Ferrand(to RD)the French government IDEX-ISITE initiative 16-IDEX-0001(to RD)The Fondation pour la Recherche Médicale(FRM)(to SM).
文摘While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,which major classes refer to inflammatory,neuropathic,and idiopathic pain.It is frequent,with up to a third of the population that may suffer at one point from chronic pain.It is often associated with other pathologies,including sleep disorders,anxiety,depression,and is still difficult to treat.It thus represents a significant burden in terms of health and societal impact(Tracey et al.,2019).The mechanisms of chronic pain involve multiple diverse pathways in both the peripheral and central nervous systems(CNS),reflecting its multifaceted biology.Indeed,research over the past decades has established that central sensitization(enhancement in the function of neurons and circuits in central nociceptive pathways),in particular within the dorsal horn,the first central relay of nociceptive inputs plays a key role in the chronicity of pain(Latremoliere and Woolf,2009).
文摘Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kgbw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF_(2α))level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF_(2α)level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF_(2α)levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF_(2α)level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.
文摘Abdominal pain is the most common symptom of chronic pancreatitis(CP)and is often debilitating for patients and very difficult to treat.To date,there exists no cure for the disease.Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events.Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain.The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders,exocrine pancreatic insufficiency,mineral bone disease,frailty,and malnutrition,are in its early stages.Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain,as well as to improve pain management.Despite the array of tools available,many therapeutic options for the management of CP pain provide incomplete relief.There still remains much to discover about the neural regulation of pancreas-related pain.In this review,we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain.These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management,and identification of potential future therapies.
文摘Objective To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome(IBS)visceral hyperalgesia model rats and its regulatory effect on P2X3 receptors in the spinal cord,anterior cingutate cortex(ACC)and thalamic ventral posterolateral nucleus(VPL).Methods Thirty 8-day-old newborn rats were randomly divided into a normal group(n=6)and a modeling group(n=24)according to the completely random number table method.Rats in the normal group were bred routinely,and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention(CRD)in stimulation method.Rats successfully modelled were re-divided into a model group,a mild moxibustion group,a P2X3 receptor antagonist group,and a normal saline group according to the completely random number table method with 6 rats in each group.Rats in each group received corresponding interventions from the 37-day old,once a day for 7 consecutive days.Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord,ACC and VPL of rats.Results Under different intensities of CRD stimulation,the abdominal withdrawal reflex(AWR)scores of the model group were significantly increased versus the normal group(all P<0.05);the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group(all P<0.01).The P2X3 protein expressions in rat spinal cord,ACC and VPL tissues of the model group were significantly increased versus the normal group(all P<0.01);the P2X3 protein expressions in rat spinal cord,ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group(all P<0.01).Conclusion Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord,ACC,and VPL tissues of IBS visceral hyperalgesia model rats,which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.
