BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics bloc...BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE： To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS： Thirty-five Spragne Dawley （SD） rats, weighing 200 - 250 g, were randomly divided into four groups： control group （n =5）, simple sciatic nerve transection group （n =10）, peripheral nerve block before and after sciatic nerve transection groups （n =10）. All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods： 3 and 7 days （n =5） respectively. Mouse anti-GAP-43 monoclonal antibody （Sigma Co., Ltd.）, supervision TM anti-mouse reagent （HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai）, and HMIAS-100 image analysis system （Qianping Image Engineering Company, Tongji Medical University） were employed in this study. METHODS： This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE： Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS： All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats （t =8.806, 6.771, P 〈 0.01）. Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats （P 〉 0.05）. CONCLUSION： Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.展开更多
BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthe...BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation. OBJECTIVE： To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 （GAP-43） and nerve growth factor （NGF） in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury. DESIGN, TIME AND SETTING： A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou University Medical College from September 2006 to September 2007. MATERIALS： COX-2 inhibitor, Iornoxicam, was purchased from Nycomed Pharmaceutical （Austria）; rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China. METHODS： A total of 50 adult, Wistar rats were randomly assigned to four groups： normal control （n = 5）, model （n = 15）, normal saline control （n = 15）, and Iornoxicam treatment （n =15）. With exception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods： 3, 7 and 14 days （n = 5）, respectively. Rats in the Iornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline. MAIN OUTCOME MEASURES： Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats. RESULTS： The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats （P 〈 0.01）, while the relative gray values in the Iomoxicam treatment group were significantly less than the model and normal saline control groups （P 〈 0.01）. Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and Iornoxicam treatment groups, and were significantly less than the normal control group （P 〈 0.05）. In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the Iornoxicam treatment group compared with the model and normal saline control groups （P 〈 0.05）. CONCLUSION： Intraperitoneal injection of the COX-2 inhibitor Iornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the increased expression of GAP-43 and NGF.展开更多
椎间盘源性腰痛(discogenic low back pain,DLBP)是临床上最常见的腰痛类型,约39%的慢性腰痛是由于椎间盘病变引起的。DLBP有着长期、持续、反复的特点,影响病人生活质量和工作效率,对社会也造成了巨大的负担。既往临床上DLBP的治疗方...椎间盘源性腰痛(discogenic low back pain,DLBP)是临床上最常见的腰痛类型,约39%的慢性腰痛是由于椎间盘病变引起的。DLBP有着长期、持续、反复的特点,影响病人生活质量和工作效率,对社会也造成了巨大的负担。既往临床上DLBP的治疗方法只能简单缓解疼痛症状并不能治疗椎间盘破裂。近年来富血小板血浆(platelet-rich plasma,PRP)在再生医学领域的应用越来越广泛,体外细胞及动物研究表明其有显著的促椎间盘再生作用。本文以自体PRP在DLBP治疗中的应用进展进行综述,以进一步增强对于DLBP致病机制的认识,并结合自体PRP在临床中的广泛应用,以此为临床DLBP的治疗提供参考。展开更多
目的:寻找诊断糖尿病神经病理性疼痛(DPNP)的生物标记物,以便于DPNP患者的诊断和个性化护理干预。方法:回顾性分析2022年1月—2023年5月收治的2型糖尿病(T2DM)患者,根据有无DPNP分为DPNP组(53例)和无DPNP组(76例)。比较两组间血糖相关...目的:寻找诊断糖尿病神经病理性疼痛(DPNP)的生物标记物,以便于DPNP患者的诊断和个性化护理干预。方法:回顾性分析2022年1月—2023年5月收治的2型糖尿病(T2DM)患者,根据有无DPNP分为DPNP组(53例)和无DPNP组(76例)。比较两组间血糖相关实验室指标和各细胞因子等的差异,观察NGF和TNF-α与各实验室指标的相关性。运用受试者工作特征(ROC)曲线比较不同标记物在DPNP诊断中的价值。结果:DPNP组的血清神经生长因子(NGF)水平显著低于无DPNP组,差异有统计学意义(P<0.05)。多因素分析结果显示,NGF水平和肿瘤坏死因子α(TNF-α)水平是诊断DPNP的独立危险因素。相关性分析显示,NGF和TNF-α水平与糖基化血红蛋白(HbAlc)、空腹C肽(FCP)、餐后2 h C肽(2 h CP)和24 h尿微量白蛋白排泄(UME)均密切相关(P<0.05)。ROC分析结果显示,NGF的曲线下面积(AUC)显著高于TNF-α的AUC(P<0.05)。结论:NGF和TNF-α是诊断DPNP的关键细胞因子,对于诊断为DPNP的患者除积极控制血糖外,还需早期给予足部护理、运动护理、健康宣教、心理护理等个体化护理干预措施。展开更多
BACKGROUND： Ketamine is a noncompetitive N-methyl-D-aspartate （NMDA） receptor antagonists and plays an important role in the treatment of pain. OBJECTIVE： To analyze the preemptive analgesic effects of different d...BACKGROUND： Ketamine is a noncompetitive N-methyl-D-aspartate （NMDA） receptor antagonists and plays an important role in the treatment of pain. OBJECTIVE： To analyze the preemptive analgesic effects of different doses of ketamine on growth-associated protein-43 （GAP43） expression in dorsal root ganglion in a rat model of chronic sciatic nerve constricted injury, and to study the differences between high-dose and low-dose ketamine DESIGN： Randomized controlled animal study. SETTING： Medical College of Shantou University. MATERIALS： Thirty-five adult male Sprague Dawley rats were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Ketamine hydrochloride injection was provided by Hengrui Pharmaceutical Co., Ltd., Jiangsu. METHODS： This study was performed at the Immunological Laboratory, Medical College of Shantou University from September to December 2006. Model of chronic sciatic nerve constricted injury： after anesthesia, the right sciatic nerve was exposed and ligated l-cm distal to the ischiadic tuberosity with a No. 3-0 cat gut suture. Grouping and intervention： 35 rats were randomly divided into 4 groups： normal control group （n = 5）, chronic constriction injury （CCI） group （n = 10）, low-dose ketamine group （n = 10）, and high-dose ketamine group （n = 10）. Rats in the normal control group did not undergo any surgery or drug intervention. Rats in the CCI group received intraperitoneal injection of saline （1 mL）, and their sciatic nerves were ligated after 10 minutes. Rats in the low-dose ketamine group underwent intraperitoneal injection of ketamine （25 mg/kg） 10 minutes prior to ligation of sciatic nerve; while, rats in the high-dose ketamine group were given intraperitoneal injection of ketamine （50 mg/kg） 10 minutes prior to ligation of sciatic nerve. On the third and the seventh days after surgery, dorsal root ganglion were resected from the sciatic nerve and cut into sections. MAIN OUTCOME MEASURES： GAP-43 expression in dorsal root ganglion was detected by immunohistochemistry and image analysis system, as well as semi-quantitative analysis. RESULTS： Thirty-five Sprague Dawley rats were included in the final analysis. Qualitative analysis： GAP-43 expression in the CCI group was higher than in the normal control group. Quantitative analysis： after three post-operative days, GAP-43 expression in the CCI group was significantly higher than in the normal control group （t = 22.919, 7.319, P 〈 0.05）. GAP-43 expression in the low-dose and high-dose ketamine group was significantly lower than in the CCI group （t = 11.166, 26.474, P 〈 0.05）. After seven postoperative days, GAP-43 expression in the low-dose and high-dose ketamine groups was significantly lower than in the CCI group （t = 2.382, 5.016, P 〈 0.05）. CONCLUSION： Preoperative administration of ketamine inhibited the increased GAP-43 expression in dorsal root ganglion during neuropathic pain.展开更多
Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors...Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V(HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100^(th) position of mature NGF resulting in a change of residue from arginine to tryptophan(R100W). Although those HSAN V patients associated with the NGF^(R100W) mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGF^(R100W) mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGF^(R100W) provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGF^(R100W) no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGF^(R100W) mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGF^(R100W) mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review.展开更多
Objective:To investigate the inhibition effect of siRNA interference on NGF induced by inflammatory factor IL-6,and JUL—1 so as to provide novel targets for clinical treatment of discogenic low back pain.Methods:The ...Objective:To investigate the inhibition effect of siRNA interference on NGF induced by inflammatory factor IL-6,and JUL—1 so as to provide novel targets for clinical treatment of discogenic low back pain.Methods:The intervertebral disc nucleus and annulus fibrosus cells of rats were separated-The cells were co-cultured with different concentrations(10 nmol/L,20nmol/L,50 nmol/L,100 nmol/L)of IL-6 and IL-1β.The NGF-siRNA was leaded into the cocultured cells with its import ability assessed by flow cytometry instrument tests,hefore and after which the NCF mRNA expression was detected by real-time Q-PCR and the NGF content was detected by ELISA.Results:Flow cytometry instrument test results showed that the NGFsiRNA cell conversion rate was 99.8%.Real-time Q-PCR detection results showed that compared with negative control group,the NGF mRNA expression of co-cultured cells treated by 10 nmol/L,20 nmol/L,50 nmol/L,100 nmol/L IL-6 and IL-1βwere respectively raised 3.4,3.7,4.7,3.7 times which were all significantly down-regulated after the import of NGF-siRNA.EILSA detection results showed that compared with negative control group,the NGF content of cocultured medium treated by 10 nmol/L,20 nmol/L,50 nmol/L,100 nmol/L I-L6 and IL-1βwere respectively raised 2.9,3.3,4.5,7.4 times which were all significantly decreased after the import of NGF-siRNA.Conclusions:These molecular biological results suggest that inflammatory factor IL-6 and IL-1βcould stimulate NCF on intervertebral disc cells in vitro culture model and its efficiency is concentration dependent,while siRNA interference can inhibit the stimulation effect of IL-6 and IL-1βon intervertebral disc cell,which provides a new targets for the clinical treatment of discogenic low back pain.展开更多
目的:探讨重组人表皮生长因子(rh-EGF)外用溶液治疗放射性口腔黏膜炎(RIOM)的效果。方法:选取2020年1月—2022年3月89例接受放疗并出现RIOM的头颈部肿瘤患者作为研究对象,根据随机数表法分为对照组(n=44)和研究组(n=45)。对照组接受地...目的:探讨重组人表皮生长因子(rh-EGF)外用溶液治疗放射性口腔黏膜炎(RIOM)的效果。方法:选取2020年1月—2022年3月89例接受放疗并出现RIOM的头颈部肿瘤患者作为研究对象,根据随机数表法分为对照组(n=44)和研究组(n=45)。对照组接受地塞米松+庆大霉素+利多卡因稀释液漱口,研究组在对照组治疗基础上加用rh-EGF治疗。采用数字评价量表(numerical rating scale,NRS)和成人癌症生存者生命质量量表(quality of life in adult cancer survivors,QLACS)评估两组口腔疼痛程度与生活质量。比较两组疗效、口腔疼痛及生活质量的差异。结果:研究组近期总有效率为95.56%(43/45),而对照组仅77.27%(34/44),两组比较差异有统计学意义(χ^(2)=7.299,P=0.026)。两组治疗前NRS、QLACS评分比较,差异均无统计学意义(P>0.05);研究组治疗后NRS、QLACS评分均低于对照组,且差异均有统计学意义(P<0.05)。结论:RIOM患者采用重组人表皮生长因子治疗,可以有效缓解疼痛,提高治疗效果,提高生活质量,值得推广应用。展开更多
基金the Natural Science Foundation of Guangdong Province, No.034628
文摘BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE： To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS： Thirty-five Spragne Dawley （SD） rats, weighing 200 - 250 g, were randomly divided into four groups： control group （n =5）, simple sciatic nerve transection group （n =10）, peripheral nerve block before and after sciatic nerve transection groups （n =10）. All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods： 3 and 7 days （n =5） respectively. Mouse anti-GAP-43 monoclonal antibody （Sigma Co., Ltd.）, supervision TM anti-mouse reagent （HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai）, and HMIAS-100 image analysis system （Qianping Image Engineering Company, Tongji Medical University） were employed in this study. METHODS： This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE： Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS： All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats （t =8.806, 6.771, P 〈 0.01）. Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats （P 〉 0.05）. CONCLUSION： Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.
基金Supported by:the Scientific Research Program of Xiamen Science and Technology Bureau,No. 3502Z20077074
文摘BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation. OBJECTIVE： To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 （GAP-43） and nerve growth factor （NGF） in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury. DESIGN, TIME AND SETTING： A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou University Medical College from September 2006 to September 2007. MATERIALS： COX-2 inhibitor, Iornoxicam, was purchased from Nycomed Pharmaceutical （Austria）; rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China. METHODS： A total of 50 adult, Wistar rats were randomly assigned to four groups： normal control （n = 5）, model （n = 15）, normal saline control （n = 15）, and Iornoxicam treatment （n =15）. With exception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods： 3, 7 and 14 days （n = 5）, respectively. Rats in the Iornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline. MAIN OUTCOME MEASURES： Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats. RESULTS： The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats （P 〈 0.01）, while the relative gray values in the Iomoxicam treatment group were significantly less than the model and normal saline control groups （P 〈 0.01）. Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and Iornoxicam treatment groups, and were significantly less than the normal control group （P 〈 0.05）. In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the Iornoxicam treatment group compared with the model and normal saline control groups （P 〈 0.05）. CONCLUSION： Intraperitoneal injection of the COX-2 inhibitor Iornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the increased expression of GAP-43 and NGF.
文摘椎间盘源性腰痛(discogenic low back pain,DLBP)是临床上最常见的腰痛类型,约39%的慢性腰痛是由于椎间盘病变引起的。DLBP有着长期、持续、反复的特点,影响病人生活质量和工作效率,对社会也造成了巨大的负担。既往临床上DLBP的治疗方法只能简单缓解疼痛症状并不能治疗椎间盘破裂。近年来富血小板血浆(platelet-rich plasma,PRP)在再生医学领域的应用越来越广泛,体外细胞及动物研究表明其有显著的促椎间盘再生作用。本文以自体PRP在DLBP治疗中的应用进展进行综述,以进一步增强对于DLBP致病机制的认识,并结合自体PRP在临床中的广泛应用,以此为临床DLBP的治疗提供参考。
文摘目的:寻找诊断糖尿病神经病理性疼痛(DPNP)的生物标记物,以便于DPNP患者的诊断和个性化护理干预。方法:回顾性分析2022年1月—2023年5月收治的2型糖尿病(T2DM)患者,根据有无DPNP分为DPNP组(53例)和无DPNP组(76例)。比较两组间血糖相关实验室指标和各细胞因子等的差异,观察NGF和TNF-α与各实验室指标的相关性。运用受试者工作特征(ROC)曲线比较不同标记物在DPNP诊断中的价值。结果:DPNP组的血清神经生长因子(NGF)水平显著低于无DPNP组,差异有统计学意义(P<0.05)。多因素分析结果显示,NGF水平和肿瘤坏死因子α(TNF-α)水平是诊断DPNP的独立危险因素。相关性分析显示,NGF和TNF-α水平与糖基化血红蛋白(HbAlc)、空腹C肽(FCP)、餐后2 h C肽(2 h CP)和24 h尿微量白蛋白排泄(UME)均密切相关(P<0.05)。ROC分析结果显示,NGF的曲线下面积(AUC)显著高于TNF-α的AUC(P<0.05)。结论:NGF和TNF-α是诊断DPNP的关键细胞因子,对于诊断为DPNP的患者除积极控制血糖外,还需早期给予足部护理、运动护理、健康宣教、心理护理等个体化护理干预措施。
文摘BACKGROUND： Ketamine is a noncompetitive N-methyl-D-aspartate （NMDA） receptor antagonists and plays an important role in the treatment of pain. OBJECTIVE： To analyze the preemptive analgesic effects of different doses of ketamine on growth-associated protein-43 （GAP43） expression in dorsal root ganglion in a rat model of chronic sciatic nerve constricted injury, and to study the differences between high-dose and low-dose ketamine DESIGN： Randomized controlled animal study. SETTING： Medical College of Shantou University. MATERIALS： Thirty-five adult male Sprague Dawley rats were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Ketamine hydrochloride injection was provided by Hengrui Pharmaceutical Co., Ltd., Jiangsu. METHODS： This study was performed at the Immunological Laboratory, Medical College of Shantou University from September to December 2006. Model of chronic sciatic nerve constricted injury： after anesthesia, the right sciatic nerve was exposed and ligated l-cm distal to the ischiadic tuberosity with a No. 3-0 cat gut suture. Grouping and intervention： 35 rats were randomly divided into 4 groups： normal control group （n = 5）, chronic constriction injury （CCI） group （n = 10）, low-dose ketamine group （n = 10）, and high-dose ketamine group （n = 10）. Rats in the normal control group did not undergo any surgery or drug intervention. Rats in the CCI group received intraperitoneal injection of saline （1 mL）, and their sciatic nerves were ligated after 10 minutes. Rats in the low-dose ketamine group underwent intraperitoneal injection of ketamine （25 mg/kg） 10 minutes prior to ligation of sciatic nerve; while, rats in the high-dose ketamine group were given intraperitoneal injection of ketamine （50 mg/kg） 10 minutes prior to ligation of sciatic nerve. On the third and the seventh days after surgery, dorsal root ganglion were resected from the sciatic nerve and cut into sections. MAIN OUTCOME MEASURES： GAP-43 expression in dorsal root ganglion was detected by immunohistochemistry and image analysis system, as well as semi-quantitative analysis. RESULTS： Thirty-five Sprague Dawley rats were included in the final analysis. Qualitative analysis： GAP-43 expression in the CCI group was higher than in the normal control group. Quantitative analysis： after three post-operative days, GAP-43 expression in the CCI group was significantly higher than in the normal control group （t = 22.919, 7.319, P 〈 0.05）. GAP-43 expression in the low-dose and high-dose ketamine group was significantly lower than in the CCI group （t = 11.166, 26.474, P 〈 0.05）. After seven postoperative days, GAP-43 expression in the low-dose and high-dose ketamine groups was significantly lower than in the CCI group （t = 2.382, 5.016, P 〈 0.05）. CONCLUSION： Preoperative administration of ketamine inhibited the increased GAP-43 expression in dorsal root ganglion during neuropathic pain.
文摘Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V(HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100^(th) position of mature NGF resulting in a change of residue from arginine to tryptophan(R100W). Although those HSAN V patients associated with the NGF^(R100W) mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGF^(R100W) mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGF^(R100W) provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGF^(R100W) no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGF^(R100W) mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGF^(R100W) mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review.
基金supported by Shandong Province Natural Science Foundation(28172a2)
文摘Objective:To investigate the inhibition effect of siRNA interference on NGF induced by inflammatory factor IL-6,and JUL—1 so as to provide novel targets for clinical treatment of discogenic low back pain.Methods:The intervertebral disc nucleus and annulus fibrosus cells of rats were separated-The cells were co-cultured with different concentrations(10 nmol/L,20nmol/L,50 nmol/L,100 nmol/L)of IL-6 and IL-1β.The NGF-siRNA was leaded into the cocultured cells with its import ability assessed by flow cytometry instrument tests,hefore and after which the NCF mRNA expression was detected by real-time Q-PCR and the NGF content was detected by ELISA.Results:Flow cytometry instrument test results showed that the NGFsiRNA cell conversion rate was 99.8%.Real-time Q-PCR detection results showed that compared with negative control group,the NGF mRNA expression of co-cultured cells treated by 10 nmol/L,20 nmol/L,50 nmol/L,100 nmol/L IL-6 and IL-1βwere respectively raised 3.4,3.7,4.7,3.7 times which were all significantly down-regulated after the import of NGF-siRNA.EILSA detection results showed that compared with negative control group,the NGF content of cocultured medium treated by 10 nmol/L,20 nmol/L,50 nmol/L,100 nmol/L I-L6 and IL-1βwere respectively raised 2.9,3.3,4.5,7.4 times which were all significantly decreased after the import of NGF-siRNA.Conclusions:These molecular biological results suggest that inflammatory factor IL-6 and IL-1βcould stimulate NCF on intervertebral disc cells in vitro culture model and its efficiency is concentration dependent,while siRNA interference can inhibit the stimulation effect of IL-6 and IL-1βon intervertebral disc cell,which provides a new targets for the clinical treatment of discogenic low back pain.
文摘目的:探讨重组人表皮生长因子(rh-EGF)外用溶液治疗放射性口腔黏膜炎(RIOM)的效果。方法:选取2020年1月—2022年3月89例接受放疗并出现RIOM的头颈部肿瘤患者作为研究对象,根据随机数表法分为对照组(n=44)和研究组(n=45)。对照组接受地塞米松+庆大霉素+利多卡因稀释液漱口,研究组在对照组治疗基础上加用rh-EGF治疗。采用数字评价量表(numerical rating scale,NRS)和成人癌症生存者生命质量量表(quality of life in adult cancer survivors,QLACS)评估两组口腔疼痛程度与生活质量。比较两组疗效、口腔疼痛及生活质量的差异。结果:研究组近期总有效率为95.56%(43/45),而对照组仅77.27%(34/44),两组比较差异有统计学意义(χ^(2)=7.299,P=0.026)。两组治疗前NRS、QLACS评分比较,差异均无统计学意义(P>0.05);研究组治疗后NRS、QLACS评分均低于对照组,且差异均有统计学意义(P<0.05)。结论:RIOM患者采用重组人表皮生长因子治疗,可以有效缓解疼痛,提高治疗效果,提高生活质量,值得推广应用。
