Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
Objectives: Chronic pain is a severe complication of mesh-based inguinal hernia repair. Pain upon ejaculation, testicular touch sensitivity and dysuria are apparent. Regarding the large amount of patients undergoing l...Objectives: Chronic pain is a severe complication of mesh-based inguinal hernia repair. Pain upon ejaculation, testicular touch sensitivity and dysuria are apparent. Regarding the large amount of patients undergoing laparoscopic hernia repair, the problem seems quite evident. In this prospective, clinical, randomized, double-blind study we intended to investigate the biocompatibility of three different meshes and their influence on urological affections after operative procedure. Methods: 180 male patients with primary inguinal hernia undergoing TAPP were randomized for using a heavyweight (108 g/m2), double-filament PP mesh (Prolene, 10 9 15 cm, group A, n = 60), a multifilament, heavyweight variant (116 g/m2) of PP mesh (Serapren, 10 9 15 cm, group B, n = 60), or a composite mesh (polyglactin and PP) (Vypro II, 10 9 15 cm, group C, n = 60). We compared in terms of complications (seromas, recurrence rate), urological affections and life quality (SF-36 Health Survey). The follow-up period was 60 months. Results: Convalescence in group A was slower than in groups B and C: mean-term values of the visual scales for pain development were significantly (p th week postoperatively. There were no significant differences between groups B and C. Beyond the 12th post-interventional week the differences diminished. Conclusions: Independent which kind of mesh was implanted still 5% of patients suffered from urological affections 60 month later.展开更多
目的:观察电针对慢性炎性痛大鼠痛感觉及其所诱发情绪的干预效应及对前扣带皮层(Anterior Cingulate Cortex,ACC)和初级体感皮层后肢区域(Primary Somatosensory Cortex,Hindlimb Region,S1HL)磷酸化细胞外调节蛋白激酶(Phosphorylated ...目的:观察电针对慢性炎性痛大鼠痛感觉及其所诱发情绪的干预效应及对前扣带皮层(Anterior Cingulate Cortex,ACC)和初级体感皮层后肢区域(Primary Somatosensory Cortex,Hindlimb Region,S1HL)磷酸化细胞外调节蛋白激酶(Phosphorylated Extracellular Regulated Protein Kinases,p-ERK)表达的影响。方法:建立完全弗氏佐剂(Complete Freund′s Adjuvant,CFA)诱导的慢性炎性痛大鼠模型。痛感觉部分:将38只成年雄性SD大鼠随机分为空白组( n =11)、模型组( n =13)、电针组( n =14),在造模前1 d、模后3 d、6 d、9 d检测大鼠患足机械缩足阈(PWTs)的变化;痛情绪部分:将62只成年雄性SD大鼠,随机分为空白组( n =21)、模型组( n =21)、电针组( n =20)进行条件性位置厌恶实验(Conditioned Place Aversion,CPA)。通过自由跑动(15 min),剔除不符合条件的大鼠,造模前1 d进行条件化前训练(45 min),模后2 h和第2天进行条件化训练(45 min),模后第3天、9天进行检测(15 min)。两部分电针组大鼠均在造模后3 d^9 d进行电针干预,选取双侧“后三里”穴,刺激参数:2/100 Hz疏密波,初始电流强度1 mA,后每10 min增加0.5 mA,共30 min,1次/d,造模后第10天取材,采用免疫荧光法(IF)和免疫印迹法(WB)检测大鼠ACC、S1HL的p-ERK的表达情况。结果:PWTs结果显示,造模后第3天、第6天、第9天,模型组与电针组大鼠PWTs较空白组显著降低( P <0.01),第9天电针组PWTs较模型组显著升高( P <0.01)。CPA检测结果显示,造模后第3天,模型组和电针组CPA score值(大鼠在条件箱停留时间差,Pre-post)较空白组显著升高( P <0.01),造模后第9天,模型组CPA score值较空白组显著升高( P <0.01),电针组CPA score值较模型组显著降低( P <0.01)。与造模后第3比较,造模后第9天模型组CPA score值显著增加( P <0.01),电针组显著降低( P <0.05)。IF检测结果显示,在左侧S1HL,模型组p-ERK免疫阳性细胞的表达较空白组和电针组有上升趋势,在右侧S1HL和双侧ACC,模型组p-ERK免疫阳性细胞的表达较空白组和电针组均显著升高( P <0.01)。WB结果显示,在双侧S1HL,模型组p-ERK1/2蛋白表达与空白组比较,差异无统计学意义。在左侧S1HL,电针组p-ERK1/2蛋白水平与模型组比较明显降低( P <0.05),在右侧S1HL,电针组p-ERK2蛋白水平与模型组比较明显降低( P <0.05),在双侧ACC区,模型组p-ERK1/2蛋白水平较空白组有上升趋势,电针组p-ERK1/2蛋白水平较模型组有下降趋势。结论:电针可提高CFA模型大鼠机械痛阈并缓解CFA大鼠厌恶情绪;该效应可能与其下调右侧S1HL中p-ERK表达水平和下调双侧ACC的p-ERK表达水平有关。展开更多
基金supported by the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
文摘Objectives: Chronic pain is a severe complication of mesh-based inguinal hernia repair. Pain upon ejaculation, testicular touch sensitivity and dysuria are apparent. Regarding the large amount of patients undergoing laparoscopic hernia repair, the problem seems quite evident. In this prospective, clinical, randomized, double-blind study we intended to investigate the biocompatibility of three different meshes and their influence on urological affections after operative procedure. Methods: 180 male patients with primary inguinal hernia undergoing TAPP were randomized for using a heavyweight (108 g/m2), double-filament PP mesh (Prolene, 10 9 15 cm, group A, n = 60), a multifilament, heavyweight variant (116 g/m2) of PP mesh (Serapren, 10 9 15 cm, group B, n = 60), or a composite mesh (polyglactin and PP) (Vypro II, 10 9 15 cm, group C, n = 60). We compared in terms of complications (seromas, recurrence rate), urological affections and life quality (SF-36 Health Survey). The follow-up period was 60 months. Results: Convalescence in group A was slower than in groups B and C: mean-term values of the visual scales for pain development were significantly (p th week postoperatively. There were no significant differences between groups B and C. Beyond the 12th post-interventional week the differences diminished. Conclusions: Independent which kind of mesh was implanted still 5% of patients suffered from urological affections 60 month later.
文摘目的:观察电针对慢性炎性痛大鼠痛感觉及其所诱发情绪的干预效应及对前扣带皮层(Anterior Cingulate Cortex,ACC)和初级体感皮层后肢区域(Primary Somatosensory Cortex,Hindlimb Region,S1HL)磷酸化细胞外调节蛋白激酶(Phosphorylated Extracellular Regulated Protein Kinases,p-ERK)表达的影响。方法:建立完全弗氏佐剂(Complete Freund′s Adjuvant,CFA)诱导的慢性炎性痛大鼠模型。痛感觉部分:将38只成年雄性SD大鼠随机分为空白组( n =11)、模型组( n =13)、电针组( n =14),在造模前1 d、模后3 d、6 d、9 d检测大鼠患足机械缩足阈(PWTs)的变化;痛情绪部分:将62只成年雄性SD大鼠,随机分为空白组( n =21)、模型组( n =21)、电针组( n =20)进行条件性位置厌恶实验(Conditioned Place Aversion,CPA)。通过自由跑动(15 min),剔除不符合条件的大鼠,造模前1 d进行条件化前训练(45 min),模后2 h和第2天进行条件化训练(45 min),模后第3天、9天进行检测(15 min)。两部分电针组大鼠均在造模后3 d^9 d进行电针干预,选取双侧“后三里”穴,刺激参数:2/100 Hz疏密波,初始电流强度1 mA,后每10 min增加0.5 mA,共30 min,1次/d,造模后第10天取材,采用免疫荧光法(IF)和免疫印迹法(WB)检测大鼠ACC、S1HL的p-ERK的表达情况。结果:PWTs结果显示,造模后第3天、第6天、第9天,模型组与电针组大鼠PWTs较空白组显著降低( P <0.01),第9天电针组PWTs较模型组显著升高( P <0.01)。CPA检测结果显示,造模后第3天,模型组和电针组CPA score值(大鼠在条件箱停留时间差,Pre-post)较空白组显著升高( P <0.01),造模后第9天,模型组CPA score值较空白组显著升高( P <0.01),电针组CPA score值较模型组显著降低( P <0.01)。与造模后第3比较,造模后第9天模型组CPA score值显著增加( P <0.01),电针组显著降低( P <0.05)。IF检测结果显示,在左侧S1HL,模型组p-ERK免疫阳性细胞的表达较空白组和电针组有上升趋势,在右侧S1HL和双侧ACC,模型组p-ERK免疫阳性细胞的表达较空白组和电针组均显著升高( P <0.01)。WB结果显示,在双侧S1HL,模型组p-ERK1/2蛋白表达与空白组比较,差异无统计学意义。在左侧S1HL,电针组p-ERK1/2蛋白水平与模型组比较明显降低( P <0.05),在右侧S1HL,电针组p-ERK2蛋白水平与模型组比较明显降低( P <0.05),在双侧ACC区,模型组p-ERK1/2蛋白水平较空白组有上升趋势,电针组p-ERK1/2蛋白水平较模型组有下降趋势。结论:电针可提高CFA模型大鼠机械痛阈并缓解CFA大鼠厌恶情绪;该效应可能与其下调右侧S1HL中p-ERK表达水平和下调双侧ACC的p-ERK表达水平有关。
