Alterations in pain processing circuitries in episodic migraine

BackgroundThe precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.MethodsFunctional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.ResultsDespite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.ConclusionsThese data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.     

下丘脑错构瘤的MRI诊断

目的探讨MRI对下丘脑错构瘤的诊断价值,提高对下丘脑错构瘤的MRI表现和临床表现的认识。资料与方法回顾性分析8例下丘脑错构瘤的MRI和临床表现资料。其中男5例,女3例,年龄1．8-12岁。全部病例在3岁前均出现临床症状,其中2例在6个月前出现症状,临床表现为性早熟7例,痴笑样癫痫4例。8例均行MRI平扫和增强扫描。结果MRI表现为鞍上下丘脑区结节或肿块,直径为9．12mm,呈类圆形、不规则形,均以宽基底附于第三脑室底部、灰结节和乳头体,T1WI上与脑灰质信号一致,T2WI上呈稍高信号,信号均匀,增强后均未见肿块强化。结论下丘脑错构瘤是导致儿童性早熟的常见原因之一,MRI是目前诊断下丘脑错构瘤的最佳影像学方法。     

人胚胎下丘脑褪黑素受体鉴定及其生物学特性

目的为证实人胚胎下丘脑是否存在褪黑素受体（ＭＲ）,以及ＧＴＰγＳ和电解质对ＭＲ的影响,以阐明褪黑素（Ｍ）生物学特性及对内分泌系统作用的机制。方法应用放射配体结合法检测人胚胎下丘脑〔１２５Ｉ〕Ｍ特异结合。结果１．人胚胎下丘脑〔１２５Ｉ〕Ｍ特异结合的Ｓｃａｔｃｈａｒｄ分析：最大结合容量（Ｂｍａｘ）为（１．１５±０．３２）ｆｍｏｌ／ｍｇ蛋白质;平衡解离常数（Ｋｄ）为（３６±８）ｐｍｏｌ／Ｌ;２．动力学分析表明为可逆性结合;３．特异性分析表明对Ｍ高度特异性;４．１０μｍｏｌ／Ｌ和５０μｍｏｌ／ＬＧＴＰγＳ使〔１２５Ｉ〕Ｍ特异结合降低,且有剂量依赖性。结论实验结果表明人胚胎下丘脑存在〔１２５Ｉ〕Ｍ特异结合位点。ＧＴＰγＳ对〔１２５Ｉ〕Ｍ特异结合有明显抑制作用,提示ＭＲ属于Ｇ蛋白系统     

下丘脑室旁核炎性细胞因子在依普利酮改善心力衰竭中的作用

目的探讨下丘脑室旁核(PVN)炎性细胞因子在依普利酮(EPL)改善心力衰竭中的作用。方法Wistar大鼠分为假手术组(n=6)、模型组(n=10)、吡咯烷二硫基甲酸盐(PDTC)组(n=10)、依普利酮组(n=10)。结扎左冠状动脉前降支诱导急性心肌梗死后心力衰竭,根据分组情况分别给予PDTC[(150 mg/(kg·d)]、依普利酮[30 mg/(kg·d)]和清洁蒸馏水灌胃,假手术组只在相同位置穿线而不结扎。6周后进行血流动力学测定,留取下丘脑、血浆标本,检测PVN内肿瘤坏死因子α(TNF-α)、核因子κB/p65(NF-κB/p65)、促肾上腺皮质激素释放激素(CRH)及血管紧张素Ⅱ(AngⅡ)的表达,并检测血浆TNF-α、去甲肾上腺素(NE)、醛固酮(ALD)水平。结果依普利酮和PDTC干预后大鼠心功能较模型组明显改善。模型组血浆ALD、NE、TNF-α水平显著升高,而依普利酮和PDTC干预后ALD、NE、TNF-α水平降低(P0.05)。模型组PVN内CRH、AngⅡ表达显著增多,依普利酮和PDTC干预后PVN内CRH、AngⅡ表达显著减少(P0.05),NF-κB/p65在依普利酮组和PDTC组的表达较模型组显著降低(P0.05)。依普利酮、PDTC可降低PVN内CRH阳性神经元表达。结论心力衰竭时大鼠PVN内炎性细胞因子表达增多,依普利酮可以改善心力衰竭大鼠心功能,与抑制PVN内炎性细胞因子过表达有关。     

The history of thought concerning the hypothalamus and its functions

Many initial studies related to identification of the boundaries and structural components, nuclei, tracts and interconnections of the hypothalamus, this continues. Early interest also focused on hypothalamic control of somatic activities and autonomie nervous system functions. During the present century chiefly, interest has developed in the hypothalamus and control of water balance, thirst, water retention and loss (diabetes insipidus and polydipsia). Its role in control of metabolism, body weight (obesity), and the regulation of body temperature has attracted the attention of physiologists for many years. Others have studied hypothalamic regulation of sex and reproductive phenomena. The hypothalamus is now attracting much attention because of its production of neuroendocrine secretions and role in control of the endocrine system. Physiologists realized very early that the hypothalamus is involved in emotional expression, in reaction to stress and adaptive adjustments. Its involvement in disease states and resistance thereto and in determining the nature of behavior has now been recognized as a matter of great importance. The origins of all these interests are reviewed.     

Central nervous system actions of atrial natriuretic factor

The recently discovered cardiac peptides, called atrial natriuretic factors (ANF), act peripherally as hormones which control fluid and electrolyte homeostasis. Their renal, adrenal and vascular effects are complemented by central nervous system (CNS) actions to inhibit vasopressin secretion, salt preference, and water intake, and to inhibit the CNS component of the hypothalamo-pituitary-adrenal axis. These central actions of ANF are thought to mirror physiological roles played by endogenous, neuronally derived ANF within the brain. ANF immunoreactivity and binding sites in the anterior pituitary gland and median eminence suggest, as well, neuroendocrine actions of the peptide. We have failed to observe direct pituitary effects of ANF on basal or stimulated pituitary hormone secretion, however, specific hypothalamic actions have been discovered. ANF infusions (IV or cerebroventricular) inhibit luteinizing hormone (LH) secretion via, at least in part, an opioid mechanism since naloxone pretreatment blocks the effect. Additionally ANF inhibits catecholamine stimulation of the release of LH-releasing factor in the median eminence. Direct effects of ANF on tuberoinfundibular dopamine neurons are suggested by the observation that the prolactin-inhibiting action of ANF is prevented by domperidone treatment and is absent following alpha methyl-p-tyrosine inhibition of tyrosine hydroxlyase activity. These recent results imply neuromodulatory actions of ANF within the CNS that are expressed via interaction with brain peptide and catecholamine systems.     

艾灸对溃疡性结肠炎大鼠结肠及下丘脑辣椒素受体1表达的影响

目的探讨麦粒灸对溃疡性结肠炎（ulcerative colitis,UC）大鼠结肠及下丘脑辣椒素受体1（VR1）的影响。方法采用免疫学方法加局部刺激制备实验性UC大鼠模型,随机分为模型组和治疗组,并与正常组作对照,治疗组施以麦粒灸治疗,采用免疫组化染色法观察结肠及下丘脑VR1的表达。结果与正常组比较,模型组大鼠结肠及下丘脑VR1的表达明显增强（P〈0.05）;与模型组比较,治疗组大鼠结肠及下丘脑VR1的表达明显降低（P〈0.05）。结论实验性UC模型大鼠结肠及下丘脑VR1增加,麦粒灸可以降低UC大鼠结肠及下丘脑VR1的表达。     

下丘脑NK2受体在应激介导抑郁症发生中的作用

目的 阐明神经激肽A的受体NK2在慢性不可预见性温和刺激(CUMS)所致的抑郁样行为发生、发展中的可能作用和机制.方法 SD大鼠随机分为对照组、氟西汀组和抑郁模型组3组,行为学检测后,氟西汀组和抑郁模型组均给予孤养+CUMS造成大鼠抑郁症模型,再次行为学检测后,氟西汀组大鼠给予氟西汀腹腔注射21d,抑郁模型组给予同体积生理盐水腹腔注射21d,再次进行行为学检测,麻醉后取大鼠下丘脑,提取组织mRNA和蛋白后,采用荧光定量PCR技术和Western Blot技术检测NK2的表达.结果 应激前3组大鼠的糖水偏好率和强迫游泳的不动时间均无统计学意义.应激后,氟西汀组和抑郁模型组大鼠的糖水摄入明显减少、强迫游泳不动时间明显增长,差异均有统计学意义(P＜0.05).而给予氟西汀后,氟西汀组大鼠的糖水偏好率有所增加,强迫游泳的不动时间有所减少,与对照组比较差异无统计学意义(P＞0.05),但与抑郁组大鼠相比,差异均有统计学意义(P＜0.05).与对照组和氟西汀组比较,抑郁组下丘脑NK2受体的mRNA和蛋白的表达量明显升高,差异有统计学意义(P＜0.05),而氟西汀组与对照组相比差异无统计学意义(P＞0.05).结论 CUMS可引起大鼠行为学改变,造成大鼠抑郁模型;NK2受体的mRNA和蛋白的表达量在应激后大鼠的下丘脑中明显升高,经氟西汀干预后可恢复到正常水平,说明NK2受体与抑郁症的发生、发展过程具有相关性,在抑郁症的发病机制中可能发挥重要作用.     

电针镇痛的累积效应与大鼠下丘脑、海马蛋白激酶A表达变化的观察

目的:观察电针(EA)"足三里"-"阳陵泉"镇痛的累积效应,及大鼠下丘脑和海马细胞蛋白激酶A(PKA)活性的变化。方法:Wistar雌鼠68只,随机分为正常对照组、慢性压迫损伤(CCI)组、CCI+EA 2天(d)组、CCI+EA 2周(w)组、去卵巢(OVX)+CCI组、OVX+CCI+EA 2 d组、OVX+CCI+EA 2 w组。Morris水迷宫法检查OVX+D-半乳糖皮下注射动物的学习记忆能力。结扎坐骨神经造成CCI慢性痛模型,电针双侧"足三里"-"阳陵泉"穴(2/15 Hz,1~2 mA,1次/d)。用辐射热照射大鼠双侧足底引起的缩腿反应潜伏期(PWL)的差值作为痛敏分数(HS)判断动物的痛反应;用免疫组化法检测下丘脑和海马组织PKA的活性。结果:CCI术后,与正常组比较,各组HS都明显升高。在单纯CCI动物上,与CCI组比,CCI术后第18天CCI+EA 2 d、CCI+EA 2 w的HS显著减小(P<0.05);CCI+EA 2 w组的HS显著低于CCI+EA 2 d组(P<0.05)。在记忆损害的动物上,OVX+CCI+EA 2 w和OVX+CCI+EA 2 d组HS明显低于OVX+CCI组(P<0.05);而两EA组间HS差异没有显著性意义(P>0.05)。CCI+EA 2 w组下丘脑室旁核(PVN)、弓状核(ARC)和视上核(SON)区PKA的灰度值均明显低于正常对照组(P<0.05),PVN和ARC区也显著低于CCI+EA 2 d组(P<0.05);OVX+CCI+EA 2 w组PVN和SON区的PKA灰度值亦均明显低于OVX+CCI组(P<0.05)。说明EA 2 w可上调PKA的表达,且具有累积性作用。OVX+CCI+EA 2 w组ARC和SON区PKA的灰度值均显著高于CCI+EA 2 w组(P<0.05),提示EA上调PKA表达的累积效应在记忆功能减退的动物上明显减弱。海马PKA的表达与SON等下丘脑核团PKA的表达趋势类似。结论:电针镇痛有累积作用,其累积效应可能与下丘脑、海马细胞PKA的表达上调有关,并且与动物神经记忆有密切关系。     

大鼠脾虚证与血清甲状腺激素及下丘脑、胸腺细胞核T3受体关系

目的：探讨脾虚证与血清甲状腺激素及下丘脑、胸腺细胞核T3受体的关系。方法：成年SD大鼠32只了随机分为4组（每组8只）：A组（正常组）、B组（脾虚组）、C组（治疗组）、D组（自复组）。采用放射配基分析法,测定各组大鼠血清T3、T4、FT3、FT4、 γ－T3 及下丘脑、胸腺细胞核T3受体的含量。结果：B、D组大鼠血清T3、T4、FT3、FT4含量均较A、C组低,有显差异（P＜0.05或P＜0.01）;各且间血清γ－T3 含量无显性差异;B、D组下丘脑、胸腺细胞T3受体含量较A、C组低,有显差异（P＜0.01）。结论：血清甲状腺激素及下丘脑、胸腺细胞核T3受体的水平降低,可导致甲状腺激素生物效应低下,经由神经内分泌免疫调节环路,削弱免疫功能,这可能是脾虚证的一种重要病机。