Opiocortin and catecholamine projections to raphe nuclei

Afferent projections to the nucleus raphe magnus (NRM) and dorsal raphe nucleus (DRN) were identified using retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin (HRP-WGA). Neurons were labeled in important nociceptive regions including periaqueductal gray (PAG), arcuate nucleus, lateral hypothalamus and medial thalamic nuclei following both injections. We have immunocytochemically identified opiocortin/WGA neurons in the arcuate nucleus following NRM and DRN injections. Dual stained catecholamine/WGA perikarya were found in zona incerta, locus coeruleus, substantia nigra, nucleus tractus solitarius and adjacent A2, C2 and C3, lateral paragigantocellular reticular nucleus/C1 and lateral reticular nucleus/A1 following DRN injections and in zona incerta, substantia nigra, nucleus tractus solitarius/A2 and lateral reticular nucleus/A1 after NRM injections. These results provide further evidence for opiocortin and catecholamine modulation of analgesia.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

P物质在谷氨酸兴奋外侧下丘脑—穹窿周围区引起的升压反…

Ｐ物质（ＳＰ）能神经元及其轴突末和受体广泛分布于很多心血管中枢。外侧下丘脑含ＳＰ能神经元,外侧下丘脑投射的升压区内又存在ＳＰ能纤维及ＳＰ受体;因此本工作检验ＳＰ在外侧下丘脑升压反应中的作用。实验显示：（１）Ｌ－谷氨酸兴奋外侧下天脑的穹窿周围区（ＬＨ／ＰＦ）或将ＳＰ分别注入各ＬＨ投射区,蓝斑（ＬＣ）、臂旁核（ＮＰＢ）或 导不管周围灰质（ＰＡＧ）均引起升压反应;（２）「Ｄ－Ｐｒｏ＾２,Ｄ－Ｐｈｅ＾７,     

大鼠延髓网状背侧亚核内5-羟色胺能、P物质样和脑啡肽样阳性终末的中枢起源

研究用荧光金（ＦＧ）逆行追踪与免疫荧光组化染色相结合的双标技术对大鼠脑干向延髓网状背侧亚核（ＳＲＤ）的５┐羟色胺（５┐ＨＴ）能、Ｐ物质（ＳＰ）能和亮氨酸┐脑啡肽（Ｌ┐ＥＮＫ）能投射进行了观察。将ＦＧ注入ＳＲＤ后,ＦＧ逆标神经元主要见于中脑导水管周围灰质、脑干中缝核簇（中缝背核、中缝正中核、中缝桥核、中缝大核、中缝隐核和中缝苍白核）、巨细胞网状核α部、延髓网状结构的内侧部和外侧部、延髓外侧网状核、三叉神经脊束核尾侧亚核和孤束核。５┐羟色胺（５┐ＨＴ）样、Ｐ物质（ＳＰ）样和亮氨酸脑啡肽（Ｌ┐ＥＮＫ）样阳性神经元主要见于中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部;此外,ＳＰ样和Ｌ┐ＥＮＫ样阳性神经元还见于臂旁核、背外侧被盖核和孤束核。ＦＧ逆标并呈５┐ＨＴ样、ＳＰ样或Ｌ┐ＥＮＫ样阳性的双标神经元也主要见于中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部,尤其是位于延髓中缝核团内的双标神经元数量较多。本研究的结果说明ＳＲＤ内的５┐ＨＴ样、ＳＰ样和Ｌ┐ＥＮＫ样阳性终末主要来自中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部,向ＳＲＤ发出５┐ＨＴ能、ＳＰ能和Ｌ┐ＥＮＫ能投射的上述核团对ＳＲＤ发挥“弥漫性伤害抑     

The thalamus of the monotremes: cyto- and myeloarchitecture and chemical neuroanatomy

Echidna and platypus brains were sectioned and stained by Nissl or myelin stains or immunocytochemically for calcium-binding proteins, gamma aminobutyric acid (GABA) or other antigens. Cyto- and myeloarchitecture revealed thalami that are fundamentally mammalian in organization, with the three principal divisions of the thalamus (epithalamus, dorsal thalamus and ventral thalamus) identifiable as in marsupials and eutherian mammals. The dorsal thalamus exhibits more nuclear parcellation than hitherto described, but lack of an internal medullary lamina, caused by splaying out of afferent fibre tracts that contribute to it in other mammals, makes identification of anterior, medial and intralaminar nuclear groups difficult. Differentiation of the ventral nuclei is evident with the ventral posterior nucleus of the platypus enormously expanded into the interior of the cerebral hemisphere, where it adopts a relationship to the striatum not seen in other mammals. Other nuclei such as the lateral dorsal become identifiable by expression of patterns of calcium-binding proteins identical to those found in other mammals. GABA cells are present in the ventral and dorsal thalamic nuclei, and in the ventral thalamus form a remarkable continuum with GABA cells of the two segments of the globus pallidus and pars reticulata of the substantia nigra.     

福尔马林致痛后大鼠中脑导水管周围灰质甲啡肽及脊髓背角P物质含量的变化

本文用免疫组化方法结合计算机图像处理技术观察大鼠后脚掌皮下注射福尔马林后脊髓背角Ｐ物质免疫阳性反应（ＳＰＬＩ）变化的节段性分布及中脑导水管周围灰质（ＰＡＧ）内甲啡肽样免疫阳性反应（ＭＥＬＩ）的变化。结果显示,注射福尔马林后,脊髓腰段（Ｌ１－２,Ｌ４－５）背角ＳＰＬＩ显著增强（Ｐ＜．０５）,３０ｍｉｎ组与６０ｍｉｎ组相比较无显著变化（Ｐ＞０．０５）;胸脊髓（Ｔ８）无显著变化（Ｐ＞０．０５）;颈脊髓背角ＳＰＬＩ有增强趋势（０．０５＜Ｐ＜０．１）;ＰＡＧ中ＭＥＬＩ减弱,腹外侧部３０ｍｉｎ组比６０ｍｉｎ组变化更大（Ｐ＜０．０５）。ＰＡＧ中ＭＥＬＩ与脊髓背角ＳＰＬＩ变化的时相关系提示福尔马林致痛引起的脊髓背角Ｐ物质的增多可能与ＰＡＧ中甲啡肽及阿片受体活动有关。     

Identification of neural circuits involved in female genital responses in the rat: a dual virus and anterograde tracing study

The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. To delineate forebrain input on PRV-labeled cells, the anterograde tracer biotinylated dextran amine was injected in the medial preoptic area (MPO), ventromedial nucleus of the hypothalamus (VMN), or the midbrain periaqueductal gray (PAG) 10 days before viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. After viral injections (4 days) in the vagina and clitoris, PRV-labeled cells were observed in the paraventricular nucleus (PVN), Barrington's nucleus, the A5 region, and the nucleus paragigantocellularis (nPGi). At 5 days postviral administration, additional PRV-labeled cells were observed within the preoptic region, VMN, PAG, and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV-positive cells primarily within the dorsal PVN of the hypothalamus, ventrolateral VMN (VMNvl), caudal PAG, and nPGi. Anterograde labeling from the VMN terminated among PRV-positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV-positive cells in the PVN, ventral hypothalamus, and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington's nucleus, and ventromedial medulla received innervation from all three sources. These studies, together, identify several central nervous system (CNS) sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl, and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses.     

Deafferentation pain and stimulation of the thalamic sensory relay nucleus: clinical and experimental study

This report summarizes our clinical experience in which the effects of both thalamic sensory relay nucleus (TSRN) and periaqueductal gray (PAG) stimulation were tested in the same series of patients with various forms of pain. The clinical data indicated that neurogenic pain due to deafferentation at the level of the peripheral nerves or the spinal cord was often controlled by TSRN stimulation but not by PAG stimulation. We also review the results of our experimental investigations in cats which were undertaken in an attempt to clarify the neurophysiologic basis of such differential clinical effects of TSRN and PAG stimulation. It appeared that abnormal hyperactivity within the trigeminal medullary dorsal horn following retrogasserian rhizotomy was far more frequently inhibited by TSRN stimulation than by PAG stimulation.     

Spontaneous unit activity of neurons within the dorsal raphe nucleus of the neonatal rat

Extracellular recordings were made of spontaneously active neurons in the dorsal raphe nucleus (DRN) of neonatal rats. The firing pattern and rate of these neurons were similar to those characterized for 5-HT-containing cells in the DRN of adult rats. Neonatal DRN cells were also inhibiteby small systematic doses of LSD, as previously described for 5-HT-containing DRN neurons in adult rats. These results indicate that DRN neurons in neonatal rats are physiologically active and display many characteristics similar to mature 5-HT-containing DRN neurons.     

Localization and morphometric analysis of masticatory muscle afferent neurons in the nucleus of the mesencephalic root of the trigeminal nerve in the cat

Injections of horseradish peroxidase (HRP) were made into the ipsilateral temporal muscle and contralateral masseter muscle of 10 cats in order to identify and characterize neurons in the nucleus of the mesencephalic root of the trigeminal nerve that innervate muscle receptors in the orofacial periphery. Neurons labelled by HRP injections and unlabelled cells from 5 control cats were measured with a computer-based image analyzer, and their position was mapped on a stereotaxic graph. Cells that innervate the masseter and temporal muscles were identified throughout the rostrocaudal extent of the nucleus. There was no indication of a somatotopic pattern nor of a specific segregation within the nucleus for cells innervating muscle receptors. The nucleus contained small, rounded unipolar neurons located primarily in the dorsal border of the periaqueductal gray (PAG) matter in the rostral part of the nucleus and larger oval unipolar neurons which were scattered throughout the nucleus, but were predominant in the pontine portion of the nucleus. HRP injections labelled both large and small cells, as well as occasional multipolar cells. The last-mentioned tended to be located in the lateral margins of the PAG. The mean geometric values obtained for the control group were: area 552.7 microns2 perimeter 110.3 microns; maximum diameter 36.0 microns. and diameter of an equivalent circle 26.1 microns. The mean values of the labelled neurons were: area 606.6 microns2; perimeter 100.1 microns; maximum diameter 36.0 microns, and diameter of an equivalent circle 27.2 microns.     

Identifying cardiovascular neurocircuitry involved in the exercise pressor reflex in humans using functional neurosurgery

Groups III and IV afferents carry sensory information regarding the muscle exercise pressor reflex, although the central integrating circuits of the reflex in humans are still poorly defined. Emerging evidence reports that the periaqueductal gray (PAG) could be a major site for integrating the "central command" component that initiates the cardiovascular response to exercise, since this area is activated during exercise and direct stimulation of the dorsal PAG causes an increase in arterial blood pressure (ABP) in humans. Here we recorded local field potentials (LFPs) from various "deep" brain nuclei during exercise tasks designed to elicit the muscle pressor reflex. The patients studied had undergone neurosurgery for the treatment of movement or pain disorders, thus had electrodes implanted stereotactically either in the PAG, subthalamic nucleus, globus pallidus interna, thalamus, hypothalamus, or anterior cingulate cortex. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental spectral frequencies. Our PAG patients showed significant increases in LFP power at frequencies from 4 to 8 Hz (P < 0.01), 8 to 12 Hz (P < 0.001), and 12 to 25 Hz (P < 0.001). These periods were associated with maintained elevated ABP during muscle occlusion following exercise. Further increases in exercise intensity resulted in corresponding increases in PAG activity and ABP. No significant changes were seen in the activity of other nuclei during occlusion. These electrophysiological data provide direct evidence for a role of the PAG in the integrating neurocircuitry of the exercise pressor reflex in humans.     

Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D -aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects.     

Ascending and descending efferent pathways of the midbrain reticular formation of the cat (radioautographic study)

By means of the anterograde axoplasmic transport technique for a mixture of labelled aminoacids (3H-leucine and 3H-proline), ascending and descending systems of the reticular formation fibers in the cat mesencephalon have been studied. Projections from the mesencephalon reticular formation (MRF) ascend to the subthalamus, lateral, dorsal and periventricular hypothalamus, to the periventricular nuclei of the midline and to the intralaminar nuclei of the thalamus. The descending pathways project to the grey substance surrounding the aqueduct of cerebrum, locus coeruleus, parabrachial region and reticular formation of the pons and medulla oblongata. The projections to the reticular nucleus of the thalamus, ventral nucleus of the external geniculate body and superior colliculi arise from the dorsal half of the MRF, and projections to the striatum, lateral reticular nucleus of the medulla oblongata--from its ventral half. Most of the structures are reciprocally connected with the MRF.     

Reward circuitry activation by noxious thermal stimuli.

Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.     

Projections of the central cerebellar nuclei to the intralaminar thalamic nuclei in cats

Projections of the central cerebellar nuclei to the intralaminar thalamic nuclei were studied in cats with the use of light and electron microscopy. Almost all intralaminar nuclei were shown to obtain cerebello-thalamic projections. The entire complex of the central cerebellar nuclei serves as a source of such projections; yet, involvement of different nuclei is dissimilar. Destruction of the central and, especially, caudal regions of the fastigial nucleus evoked in the intralaminar thalamic nuclei degenerative changes in the nerve fibers (from swelling and development of varicosities up to total fragmentation). Pathological phenomena could be noticed in the most caudal regions of the above thalamic nuclear group, including the medial dorsal nucleus. Projections of the cerebellar interpositus nucleus were directed toward nearly the same regions of the intralaminar nuclei; degeneration was more intensive (covered thecentrum medianum) when posterior regions of the interpositus nucleus were destroyed. Destruction of the lateral cerebellar nucleus evoked a similar pattern of pathological changes, but degeneration was also observed in some structures of the ventral and anterior nuclear groups of the thalamus. Electron microscopic examination showed that degeneration of dark and light types developed in the fiber preterminals and terminals. It can be concluded that the central cerebellar nuclei project not only to the ventral complex of the thalamic nuclei, but also to the anterior, medial, and intralaminar nuclear groups (rostral and caudal portions).     

Mammal-like organization of the avian midbrain central gray and a reappraisal of the intercollicular nucleus

In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG.     

Interaction of opiate peptide and noradrenalin systems: Light microscopic studies

In this light microscopic immunocyto-chemical study β-Endorphin (β-END), leu-enkephalin and dopamine-βhydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for β-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between β-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.     

刺激大鼠中脑导水管周围灰质诱发的脊髓背根电位...

When periaqueductal gray (PAG) was stimulated with concentric electrodes, a steady negative potential called PAG-DRP was recorded from L5 dorsal root. PAG-DRP with properties of spatial and temporal summation propagates decrementally along the dorsal root and is inhibited by picrotoxin. Lesions of NRM had no effect on the PAG-DRP evoked by stimulation of dorsal PAG, but showed obvious reduction up to about 40% on the PAG-DRP evoked by stimulation of ventral PAG. It is suggested that the descending inhibition of PAG includes some presynaptic inhibition and that the ventral PAG-DRP is relayed partly via NRM while the dorsal PAG-DRP is not associated with NRM.     

Lamination of spinal cells projecting to the zona incerta of rats

In this study, the lamination patterns of spinal cells projecting to the zona incerta (ZI), intralaminar nuclei and ventral posterior nucleus of the thalamus have been explored. Injections of cholera toxin subunit B or latex beads were made into the ZI, intralaminar and ventral posterior nuclei of Sprague Dawley rats. The brain and spinal cord were then aldehyde fixed and processed using standard methods. Our results show two major findings. First, after injections into the ZI, there is a distinct pattern of lamination of labelled cells in the spinal cord, a pattern that changes across the different levels. At cervical levels, labelled cells are located within the medial region of the deep dorsal horn, while at lumbar and sacral levels, they are found in the intermediate grey matter. These results are similar to those seen after injections into the intralaminar or ventral posterior nuclei, except that in the latter cases, more labelled cells are located in the superficial laminae of the dorsal horn, particularly from the ventral posterior nucleus. Second, the ZI is not associated uniformly with all spinal levels; labelling is heaviest at cervical and lightest at thoracic levels. From each thalamic injection site, labelling is noted on both sides of the spinal cord, with a clear contralateral predominance. In conclusion, the results indicate that the ZI receives a distinct set of spinal projections principally from the cervical level. The particular pattern of lamination of spinal cells projecting to the ZI suggests that the type of information relayed is from deep somatic and/or visceral structures, and probably nociceptive in nature.