Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022...Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.展开更多
Objective: This study aims to explore the effect of peer support in improving self-efficacy of rural patients with type 2 diabetes and the application of drugs to reduce the pain from diabetes. Methods: Patients with ...Objective: This study aims to explore the effect of peer support in improving self-efficacy of rural patients with type 2 diabetes and the application of drugs to reduce the pain from diabetes. Methods: Patients with type 2 diabetes in the rural area were selected and they were divided into the peer group and control group with voluntary. The patients in peer support group applied six kinds of activity patterns, while the control group was carried out with routine activities. Results: Comparison indexes for the two groups are mastering degree of related knowledge to diabetes, control compliance rate of indicators related to diabetes, and management of diabetes self-efficacy. Comparing with the control group, indexes in peer support group were significantly increased (P < 0.01). Meanwhile, in the table of diabetes distress, 17 items have been improved and the occurrence rate of painful diabetic decreased significantly (P < 0.01). Conclusion: Peer support can improve the rural patients’ self-efficacy of type 2 diabetes and decrease patients’ pain from type 2 diabetes mellitus.展开更多
Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN a...Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN and 70 patients with non-neuropathic pain were recruited from five grade III general hospitals in Guangzhou.Pain was assessed using the Leeds Assessment of Neuropathic Symptoms and Signs(LANSS),Douleur Neuropathique 4 questionnaire(DN4),and Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy(BPI-DPN).Reliability was evaluated by internal consistency of the Cronbach's a coefficient and Guttman split-half.Construct validity was analyzed by factor analysis and Spearman correlation coefficients.Sensitivity and specificity were also assessed.Results:The Cronbach's a coefficients of the LANSS,DN4,and BPI-DPN were 0.735,0.750,and 0.898,respectively.The Guttman split-half coefficients of the LANSS,DN4,and BPIDPN were 0.660,0.726,and 0.849,respectively.The cumulative contributions of the LANSS,DN4,and BPI-DPN to the total variance were 61.945%,57.010%,and 66.056%,respectively.The items of the LANSS,DN4,and BPI-DPN presented high factorial loads,ranging from 0.387 to 0.841,0.137 to 0.948,and 0.487 to 0.953,respectively.The LANSS and DN4 exhibited sensitivities of 58.0%and 82.7%,respectively,and specificity of 97.1%.Conclusions:The LANSS or DN4 can be used to detect neuropathic pain in Chinese patients with PDPN.The BPI-DPN can be employed to monitor the effectiveness of pain intervention.展开更多
Painful diabetic peripheral neuropathy is one of the common chronic complications of diabetes."Pain"is the most typical symptom in patients,which seriously affects their quality of life.Traditional Chinese m...Painful diabetic peripheral neuropathy is one of the common chronic complications of diabetes."Pain"is the most typical symptom in patients,which seriously affects their quality of life.Traditional Chinese medicine(TCM)treatment of the disease includes oral administration of Chinese medicine,TCM fumigation and acupuncture,etc.,which can significantly reduce the pain of patients and reduce the frequency of disease.Chinese decoctions regulate the imbalance of yin and yang in the human body through syndrome differentiation,so as to achieve the balance of yin and yang,which will then eliminate the disease.Chinese medicine fumigation make the medicine seep into the body from the skin to exert the medical effects,and nourish and dredge the meridians.There is no pain if the meridians are smooth flowing,there will be pain if the meridians are blocked,fumigation can be used alone or assisted by other treatment methods to enhance the efficacy.The characteristics of acupuncture are rapid painrelief,economic and convenient,and can quickly relieve pain for patients with low tolerance.展开更多
The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular factors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of prot...The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular factors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. Taking effective clinical management of neuropathic pain is based on a pharmacological treatment that has shown their limits and many side effects. The hypothesis of central sensitization inhibited by Clerodendrum formicarum, an African pharmacopoeia plant used to treat headaches, arthritis, epilepsy and chronic pain could act on astrocytes and microglial cells. The objective of this work is to study the effect of Clerodendrum formicarum (100, 150 and 200 mg/kg body weight) on astrocytes and microglial cells in a model of diabetic neuropathic pain induced by alloxan monohydrate (150 mg/kg). We noted a suppression of mechanical allodynia and mechanical hyperalgesia respectively by the Von Frey filaments test and the pressure test on the paw by the Clerodendrum formicarumextracts (ECF) at different doses from 2 h at the first injection of the ECF. After 5 days of treatment, we expressed by Western Blot bands of different proteins and by quantitative RT-PCR, we determined inhibition of the expression of GFAP, CD11b and isoforms 1 and 2 of cyclooxygenase. These results suggest that ECF inhibits the activation of astrocytes, microglial cells and cyclooxygenase signaling pathway.展开更多
OBJECTIVE:To assess efficacy of Shutangluo fang on painful diabetic peripheral neuropathy(PDPN).METHODS:Adopting stratified randomized and controlled design,82 patients with PDPN were assigned to two groups.Both group...OBJECTIVE:To assess efficacy of Shutangluo fang on painful diabetic peripheral neuropathy(PDPN).METHODS:Adopting stratified randomized and controlled design,82 patients with PDPN were assigned to two groups.Both groups continued conventional therapy.Epalrestat was administered to patients in both groups,and Shutangluo fang was given to patients in the treatment group.The treatment course lasted for 3 months.The changes before and after treatment of symptoms and signs,electrophysiological assessments were observed.RESULTS:The efficacy of the treatment group was better than the control group.The sensory nerve conduction velocity was significantly improved in the treatment group than the control group.CONCLUSIONS:Shutangluo fang is effective on PDPN.展开更多
Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lac...Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that （1） db/db mice （with a leptin receptor-null mutation and characterized by obesity and hyperglycemia） showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; （2） phosphorylated extracellular signal- regulated kinase （pERK）, but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAP- expressing astrocytes, but not in Iba-l-expressing microglia; （3） both single and consecutive （for 5 days） intrathecal injections of U0126 （2 nmol per day）, a selective MEK （an ERK kinase） inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave＇s test; and （4） db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.展开更多
tDiabetic neuropathic pain(DNP)is the most common disabling complication of diabetes.Emerging evi-dence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area;however,the...tDiabetic neuropathic pain(DNP)is the most common disabling complication of diabetes.Emerging evi-dence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area;however,the underlying molecular events remain poorly understood.Here we found that an axon guidance molecule,Netrin-3(Ntn-3),was expressed in the sensory neurons of mouse dorsal root ganglia(DRGs),and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model.Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice.In contrast,the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice.In con-clusion,our studies identified Ntn-3 as an important regula-tor of DNP pathogenesis by gating the aberrant sprouting of sensory axons,indicating that Ntn-3 is a potential druggable target for DNP treatment.展开更多
Objective： To investigate the analgesic effects of electroacupuncture （EA） at 2 and 100 Hz on type 2 diabetic neuropathic pain （DNP） and on the expressions of the P2X3 receptor and calcitonin gene-related peptide...Objective： To investigate the analgesic effects of electroacupuncture （EA） at 2 and 100 Hz on type 2 diabetic neuropathic pain （DNP） and on the expressions of the P2X3 receptor and calcitonin gene-related peptide （CGRP） in the dorsal root ganglion （DRG）. Methods： Rat type 2 DNP was induced by a high calorie and high sugar diet fed for 7 weeks, plus a single intraperitoneal injection of streptozotocin （STZ） after 5 weeks. EA at 2 and 100 Hz was carried out once every day after 7 weeks for 7 consecutive days. Body weight, serum fasting insulin （FINS）, fasting blood glucose （FBG）, insulin sensitivity index （ISI）, and paw withdrawal latency （PWL） were measured. The expressions of L4-L6 DRG P2X3 receptors and CGRP were assessed by immunofluorescence. Results： Type 2 DNP was successfully induced as shown by the increased body weight, FINS, and FBG, as well as the reduced ISI and PWL. Expressions of P2X3 receptors and CGRP in L4-L6 DRGs increased. EA at both 2 and 100 Hz relieved type 2 DNP, but the analgesic effect of EA was stronger at 2 Hz. P2X3 receptor expression decreased in L4-L6 DRGs following EA at 2 Hz and in L5 and L6 DRGs following EA at 100 Hz. EA at both 2 and 100 Hz down-regulated CGRP overexpression in L4-L6 DRGs. Conclusions： These findings indicate that EA at 2 Hz is a good option for the management of type 2 DNP. The EA effect may be related to its down-regulation of the overexpressions of the DRG P2X3 receptors and CGRP in this condition.展开更多
Neuropathic pain(NP)has become a serious global health issue and a huge clinical challenge without available effective treatment.P2 receptors family is involved in pain transmission and represents a promising target f...Neuropathic pain(NP)has become a serious global health issue and a huge clinical challenge without available effective treatment.P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention.Traditional Chinese medicine(TCM)contains multiple components which are effective in targeting different pathological mechanisms involved in NP.Different from traditional analgesics,which target a single pathway,TCMs take the advantage of multiple components and multiple targets,and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP.Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain.This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.展开更多
Background Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with d...Background Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain （DPNP） in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain. Methods This double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory （BPI） 24-hour average pain severity ratings ≥4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator＇s judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol： 5 Dimensions, Athens Insomnia Scale, and safety measures. Results Of 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively,completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups （P=0.124）. Duloxetinetreated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1,2, and 4 （P=0.004, P=0.009, and P=0.006, respectively） but not at weeks 8 （P=0.125） and 12 （P=0.107）. Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now, and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo. Duloxetine-treated patients reported nausea, somnolence, anorexia, and dysuria significantly more than placebo. Conclusions Although the primary study endpoint was not achieved, the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain. The safety profile for duloxetine is similar to that reported in other global trials.展开更多
Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontane...Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain,elaborates from generation,induction,initiation,to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism,i.e.,connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane.This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias,wounds,denervation supersensitivity,neurogenic pain(hyperalgesia and allodynia),epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years.展开更多
文摘Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.
文摘Objective: This study aims to explore the effect of peer support in improving self-efficacy of rural patients with type 2 diabetes and the application of drugs to reduce the pain from diabetes. Methods: Patients with type 2 diabetes in the rural area were selected and they were divided into the peer group and control group with voluntary. The patients in peer support group applied six kinds of activity patterns, while the control group was carried out with routine activities. Results: Comparison indexes for the two groups are mastering degree of related knowledge to diabetes, control compliance rate of indicators related to diabetes, and management of diabetes self-efficacy. Comparing with the control group, indexes in peer support group were significantly increased (P < 0.01). Meanwhile, in the table of diabetes distress, 17 items have been improved and the occurrence rate of painful diabetic decreased significantly (P < 0.01). Conclusion: Peer support can improve the rural patients’ self-efficacy of type 2 diabetes and decrease patients’ pain from type 2 diabetes mellitus.
文摘Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN and 70 patients with non-neuropathic pain were recruited from five grade III general hospitals in Guangzhou.Pain was assessed using the Leeds Assessment of Neuropathic Symptoms and Signs(LANSS),Douleur Neuropathique 4 questionnaire(DN4),and Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy(BPI-DPN).Reliability was evaluated by internal consistency of the Cronbach's a coefficient and Guttman split-half.Construct validity was analyzed by factor analysis and Spearman correlation coefficients.Sensitivity and specificity were also assessed.Results:The Cronbach's a coefficients of the LANSS,DN4,and BPI-DPN were 0.735,0.750,and 0.898,respectively.The Guttman split-half coefficients of the LANSS,DN4,and BPIDPN were 0.660,0.726,and 0.849,respectively.The cumulative contributions of the LANSS,DN4,and BPI-DPN to the total variance were 61.945%,57.010%,and 66.056%,respectively.The items of the LANSS,DN4,and BPI-DPN presented high factorial loads,ranging from 0.387 to 0.841,0.137 to 0.948,and 0.487 to 0.953,respectively.The LANSS and DN4 exhibited sensitivities of 58.0%and 82.7%,respectively,and specificity of 97.1%.Conclusions:The LANSS or DN4 can be used to detect neuropathic pain in Chinese patients with PDPN.The BPI-DPN can be employed to monitor the effectiveness of pain intervention.
基金Shaanxi Province 2020 Key Research and Development Program Project(2020SF-276)Xi'an Health Bureau Science and Technology Project(J201902018)。
文摘Painful diabetic peripheral neuropathy is one of the common chronic complications of diabetes."Pain"is the most typical symptom in patients,which seriously affects their quality of life.Traditional Chinese medicine(TCM)treatment of the disease includes oral administration of Chinese medicine,TCM fumigation and acupuncture,etc.,which can significantly reduce the pain of patients and reduce the frequency of disease.Chinese decoctions regulate the imbalance of yin and yang in the human body through syndrome differentiation,so as to achieve the balance of yin and yang,which will then eliminate the disease.Chinese medicine fumigation make the medicine seep into the body from the skin to exert the medical effects,and nourish and dredge the meridians.There is no pain if the meridians are smooth flowing,there will be pain if the meridians are blocked,fumigation can be used alone or assisted by other treatment methods to enhance the efficacy.The characteristics of acupuncture are rapid painrelief,economic and convenient,and can quickly relieve pain for patients with low tolerance.
文摘The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular factors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. Taking effective clinical management of neuropathic pain is based on a pharmacological treatment that has shown their limits and many side effects. The hypothesis of central sensitization inhibited by Clerodendrum formicarum, an African pharmacopoeia plant used to treat headaches, arthritis, epilepsy and chronic pain could act on astrocytes and microglial cells. The objective of this work is to study the effect of Clerodendrum formicarum (100, 150 and 200 mg/kg body weight) on astrocytes and microglial cells in a model of diabetic neuropathic pain induced by alloxan monohydrate (150 mg/kg). We noted a suppression of mechanical allodynia and mechanical hyperalgesia respectively by the Von Frey filaments test and the pressure test on the paw by the Clerodendrum formicarumextracts (ECF) at different doses from 2 h at the first injection of the ECF. After 5 days of treatment, we expressed by Western Blot bands of different proteins and by quantitative RT-PCR, we determined inhibition of the expression of GFAP, CD11b and isoforms 1 and 2 of cyclooxygenase. These results suggest that ECF inhibits the activation of astrocytes, microglial cells and cyclooxygenase signaling pathway.
文摘OBJECTIVE:To assess efficacy of Shutangluo fang on painful diabetic peripheral neuropathy(PDPN).METHODS:Adopting stratified randomized and controlled design,82 patients with PDPN were assigned to two groups.Both groups continued conventional therapy.Epalrestat was administered to patients in both groups,and Shutangluo fang was given to patients in the treatment group.The treatment course lasted for 3 months.The changes before and after treatment of symptoms and signs,electrophysiological assessments were observed.RESULTS:The efficacy of the treatment group was better than the control group.The sensory nerve conduction velocity was significantly improved in the treatment group than the control group.CONCLUSIONS:Shutangluo fang is effective on PDPN.
基金supported by the National Natural Science Foundation of China(3137112331121061+1 种基金30900444and 31070973)
文摘Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that （1） db/db mice （with a leptin receptor-null mutation and characterized by obesity and hyperglycemia） showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; （2） phosphorylated extracellular signal- regulated kinase （pERK）, but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAP- expressing astrocytes, but not in Iba-l-expressing microglia; （3） both single and consecutive （for 5 days） intrathecal injections of U0126 （2 nmol per day）, a selective MEK （an ERK kinase） inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave＇s test; and （4） db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY19H090030)the Science and Technology Innovation 2030-Major Project of Brain Science and Brain-like Research(2021ZD0202501)the Excellent Innovation Program of Hangzhou Municipal University in 2019,and the National Natural Science Foundation of China(82150003,91949104,and 31871022).
文摘tDiabetic neuropathic pain(DNP)is the most common disabling complication of diabetes.Emerging evi-dence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area;however,the underlying molecular events remain poorly understood.Here we found that an axon guidance molecule,Netrin-3(Ntn-3),was expressed in the sensory neurons of mouse dorsal root ganglia(DRGs),and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model.Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice.In contrast,the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice.In con-clusion,our studies identified Ntn-3 as an important regula-tor of DNP pathogenesis by gating the aberrant sprouting of sensory axons,indicating that Ntn-3 is a potential druggable target for DNP treatment.
基金Project supported by the National Natural Science Foundation of China(No.81303039)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20133322120001)+2 种基金the Zhejiang Postdoctoral Science Foundation(No.BSH1302083)the Zhejiang Province Top Key Discipline of Chinese Medicine-Acupuncture&Tuina(No.[2012]80)the Key Science and Technology Innovation Team of Zhejiang Province(No.2013TD15),China
文摘Objective： To investigate the analgesic effects of electroacupuncture （EA） at 2 and 100 Hz on type 2 diabetic neuropathic pain （DNP） and on the expressions of the P2X3 receptor and calcitonin gene-related peptide （CGRP） in the dorsal root ganglion （DRG）. Methods： Rat type 2 DNP was induced by a high calorie and high sugar diet fed for 7 weeks, plus a single intraperitoneal injection of streptozotocin （STZ） after 5 weeks. EA at 2 and 100 Hz was carried out once every day after 7 weeks for 7 consecutive days. Body weight, serum fasting insulin （FINS）, fasting blood glucose （FBG）, insulin sensitivity index （ISI）, and paw withdrawal latency （PWL） were measured. The expressions of L4-L6 DRG P2X3 receptors and CGRP were assessed by immunofluorescence. Results： Type 2 DNP was successfully induced as shown by the increased body weight, FINS, and FBG, as well as the reduced ISI and PWL. Expressions of P2X3 receptors and CGRP in L4-L6 DRGs increased. EA at both 2 and 100 Hz relieved type 2 DNP, but the analgesic effect of EA was stronger at 2 Hz. P2X3 receptor expression decreased in L4-L6 DRGs following EA at 2 Hz and in L5 and L6 DRGs following EA at 100 Hz. EA at both 2 and 100 Hz down-regulated CGRP overexpression in L4-L6 DRGs. Conclusions： These findings indicate that EA at 2 Hz is a good option for the management of type 2 DNP. The EA effect may be related to its down-regulation of the overexpressions of the DRG P2X3 receptors and CGRP in this condition.
基金supported by the National Natural Science Foundation of China(Nos.81570735,8181101216,31560276,81970749,and 81870574)
文摘Neuropathic pain(NP)has become a serious global health issue and a huge clinical challenge without available effective treatment.P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention.Traditional Chinese medicine(TCM)contains multiple components which are effective in targeting different pathological mechanisms involved in NP.Different from traditional analgesics,which target a single pathway,TCMs take the advantage of multiple components and multiple targets,and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP.Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain.This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.
文摘Background Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain （DPNP） in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain. Methods This double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory （BPI） 24-hour average pain severity ratings ≥4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator＇s judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol： 5 Dimensions, Athens Insomnia Scale, and safety measures. Results Of 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively,completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups （P=0.124）. Duloxetinetreated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1,2, and 4 （P=0.004, P=0.009, and P=0.006, respectively） but not at weeks 8 （P=0.125） and 12 （P=0.107）. Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now, and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo. Duloxetine-treated patients reported nausea, somnolence, anorexia, and dysuria significantly more than placebo. Conclusions Although the primary study endpoint was not achieved, the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain. The safety profile for duloxetine is similar to that reported in other global trials.
基金supported by a grant of the Korean Health Technology R&D Project,Ministry for Health,Welfare & Family Affairs,Republic of Korea(Grant No.A 092125)
文摘Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain,elaborates from generation,induction,initiation,to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism,i.e.,connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane.This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias,wounds,denervation supersensitivity,neurogenic pain(hyperalgesia and allodynia),epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years.
