The rostroventromedial medulla is not involved in α2-adrenoceptor-mediated antinociception in the rat

The aim of the current study was to investigate the role of the rostroventromedial medulla (RVM) in α₂-adrenoceptor-mediated antinociception. Medetomidine or clonidine, selective α₂-adrenoceptor agonists were microinjected into the RVM in unanesthetized rats with a chronic guide cannula. The antinociceptive effects were evaluated using the tail-flick and hot-plate tests. For comparison, medetomidine was microinjected into the cerebellum or the periaqueductal gray (PAG). To study the role of medullospinal pathways, the tail-flick latencies were also measured in spinalized rats. The reversal of the antinociception induced by intracerebral microinjections of medetomidine was attempted by s.c. atipamezole, a selective α₂-adrenoceptor antagonist. The reversal of the antinociception induced by systemic administration of medetomidine was attempted by microinjections of 5% lidocaine or atipamezole into the RVM. When administered into the RVM, medetomidine produced a dose-dependent (1–30 μg) antinociception in the tail-flick and hot-plate tests, which antinociceptive effect was completely reversed by atipamezole (1 mg/kg, s.c.). Also clonidine produced a dose-dependent (3–30 μg) antinociception following microinjection into the RVM. Microinjections of medetomidine into the cerebellum or the PAG produced an identical dose-response curve in the tail-flick test as that obtained following microinjection into the RVM. In spinalized rats the antinociceptive effect (tail-flick test) induced by medetomidine microinjected into the RVM was not less effective than in intact rats. Lidocaine (5%) or atipamezole (5 μg) microinjected into the RVM did not attenuate the antinociception induced by systemically administered medetomidine (100 μg/kg, s.c.). The adapting skin temperature of the tail was increased in a nonmonotonic fashion following medetomidine. The results indicate that the RVM is not a site which is critical for the α₂-adrenergic antinociception. The antinociception following intracerebral microinjections of medetomidine into the RVM, PAG or the cerebellum in the current study can be explained by a spread of the α₂-adrenoceptor agonist into the spinal level to activate directly spinal α₂-adrenoceptors. Also, the antinociception following systemic administration of medetomidine can be explained by spinal α₂-adrenergic mechanisms. The medetomidine-induced increase of the adapting skin temperature may have attenuated the medetomidine-induced increases in the response latencies to noxious heat.     

中脑导水管周围灰质在大鼠血管源性头痛模型中的作用

目的研究中脑导水管周围灰质(PAG)在血管源性头痛如偏头痛涉及的伤害觉信息的传递中的作用。方法以雄性SD大鼠(体重为220~250g)为实验对象,在手术暴露其上矢状窦(SSS)后电刺激SSS区硬脑膜制作血管性头痛的动物模型;应用免疫组织化学染色技术,观察中脑PAG原癌基因蛋白质c-fos(Fos)和一氧化氮合酶(NOS)表达的变化。结果Fos免疫反应阳性神经元和NOS免疫反应阳性神经元主要位于中脑PAG的腹外侧区,阳性细胞数头侧至尾侧逐渐增多。空白对照组、假手术对照组、刺激组每张切片的Fos阳性神经元数分别为7.2±4.2、13.6±4.3、76.0±12.3;NOS阳性神经元数分别为35.0±3.5、42.3±4.2、162.0±11.6。结论刺激大鼠SSS区硬脑膜可激活PAG,提示PAG不但参与对于伤害性感觉信息传入后的下行调节,还通过上行投射纤维与疼痛中枢丘脑发生联系。PAG可能参与血管源性头痛如偏头痛的痛觉中枢调控。     

灰色系统GM(1,1)模型在医学预测中的应用

介绍了灰色系统GM(1,1)模型的预测方法,并用该模型对学生近视率进行预测分析,拟合与外推预测的平均误差分别占实测值均数的1.43%和1.21%。本文还将灰色系统GM(1,1)模型与常见的直线回归模型和指数曲线模型进行了比较,结果表明GM(1,1)模型的预测效果较上述两种模型好。该模型所需样本量小,不需要典型的概率分布,计算简便,预测效果好,适用范围广,是一种新型预测模型。     

脑内五羟色胺与干扰素镇痛

由侧脑室或在中脑导水管周围灰质内微量注射入白细胞α-干扰素可以引起大鼠痛阈明显上升,但脑内5-HT和5-HIAA均无变化。看来干扰素的镇痛作用和脑内5-HT递质无关,它可能是不经过5-HT的释放也不和吗啡受体结合起作用的另一类型的镇痛物质。     

III. Comparison of the antinociceptive action of Mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique

In rats stereotaxically implanted with microinjection cannula in either the periaqueductal gray matter (PAG) or the medial/paramedial medullary reticular formation (MRF), microinjection of morphine, sufentanil,d-Ala²-d-Leu⁵-enkephalin (DADL) ord-Ser²- Thr⁶-leucine enkephalin (DSTLE) produced dose-dependent elevations in the response latency on tail-flick and hot plate tests. These effects were reversed by naloxone administered by microinjection into the same intracerebral site. Both mu (morphine and sufentanil) and delta (DADL and DSTLE) opioid receptor ligands produced a maximal elevation in the supraspinally mediated hot plate response when administered into either the PAG or the MRF. Similarly, mu and delta receptor ligands produced maximum elevations in the spinally mediated tail-flick response when microinjected into the PAG. In contrast, delta, but not mu, receptor agonists produced a total blockade of the tail-flick response following administraion into the MRF. Microinjection of mu (morphine) or delta (DADL) agonists into the PAG or the MRF also resulted in a naloxone-reversible inhibition of the visceral chemical evoked writhing response. These observations suggest that mu and delta opioid receptor linked systems within the MRF but not the PAG produce their antinociceptive effects by discriminable mechanisms with a differential action on spinopetal vs supraspinal modulatory systems.     

大白鼠中脑导水管周围灰质腹外侧区的传入投射——HRP逆行追踪方法研究

用HRP(horseradish peroxidase)逆行追踪标记技术,研究大白鼠中脑导水管周围灰质(PAG,periaqueductal gray)尾侧半腹外侧区的传入投射。将HRP注入PAG尾侧半的腹外侧区:①在大脑皮层内岛无颗粒层出现中等数量的标记细胞;②基底前脑内的标记细胞较多,主要分布于终纹床核、斜角带核、无名质、杏仁内侧核和腹侧苍白球,外侧隔核和伏核内也出现少量的标记细胞;③下丘脑中大量的标记细胞出现在视前内侧区、视前外侧区和下丘脑外侧区;④底丘脑和背侧丘脑的标记细胞主要分布在未定带和束分核。     

Recruitment of striatonigral disinhibitory and nigrotectal inhibitory GABAergic pathways during the organization of defensive behavior by mice in a dangerous environment with the venomous snake Bothrops alternatus (Reptilia,Viperidae)

The neuropsychopharmacological basis of fear‐ or panic‐related behavior has been the focus of several studies. Some mesencephalic tectum (MT) structures, such as the superior colliculus (SC) and dorsal periaqueductal gray matter (dPAG), are considered to be responsible for the control of defensive responses evoked during threatening situations. Furthermore, the pars reticulata of the substantia nigra (SNpr) sends inputs to the SC that can work as a sensory channel to MT neurons fundamental for the elaboration of defensive responses. The purpose of the present study was to investigate the role of striato‐nigral GABAergic inputs in the activity of nigro‐tectal outputs during the elaboration of defensive behavior using a GABA_A receptor selective blockade in the MT of mice confronted pre‐treated with Bothrops alternatus. Mice with injections of physiological saline into the SNpr and treated with a GABA_A receptor selective antagonist in the MT displayed an increase in panic‐related behavior, expressed by an increase in the duration of freezing, frequency of nonoriented escape and frequency of total escape responses during the confrontation with the snake. However, intra‐SNpr injections of cobalt chloride followed by MT injections of bicuculline caused a significant decrease in the duration of freezing and total escape responses. In addition, intra‐SNpr injections of lidocaine followed by MT injections of bicuculline caused an increase in panic‐related behavior. The results highlight the involvement of SNpr and MT structures in the organization of defensive behaviors and suggest an inhibitory control of striatonigral‐nigrotectal pathways during the elaboration of fear‐ and panic‐related behavior. Synapse 69:299–313, 2015 . © 2015 Wiley Periodicals, Inc.     

Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain‐injured patients

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum‐optimized voxel‐based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I–IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. Hum Brain Mapp 36:4897–4909, 2015. © 2015 Wiley Periodicals, Inc.     

基于灰色关联分析的芒果叶提取物抗炎作用的谱效关系

目的:探讨芒果叶提取物的高效液相色谱(HPLC)图谱中主要色谱峰与抗炎药效的相关性,为表征芒果叶抗炎作用物质基础提供依据。方法:采用HPLC法建立芒果叶不同极性提取物的指纹图谱。取昆明小鼠随机分别为模型组、地塞米松阳性对照组、芒果叶提取物100 g·kg-1组,模型组给生理盐水,其余各组给予相应药物,灌胃给药,连续5 d,经二甲苯造模后,测定耳肿胀度。数据经统计分析后,采用灰色关联分析谱效关系。结果:芒果叶不同极性溶剂提取物的HPLC指纹图谱有明显差异,从HPLC指纹图谱中共提取14个能够表征药材特征的共有峰。不同极性提取物的抗炎作用存在显著差异。与模型组比较,地塞米松组具有显著抑制小鼠耳肿胀作用(P<0.05);与模型组比较,芒果叶(红象牙和台农一号)的三氯甲烷、乙酸乙酯提取物均无显著抗炎作用,其他溶剂提取物具有显著抗炎作用(P<0.05)。灰色关联分析明确了X1,X3和芒果苷对抗炎作用贡献程度最大。结论:芒果叶提取物抗炎作用的部分物质基础是芒果苷及X1,X3峰。灰色关联是研究中药谱效关系的有效手段。