弧束核参与剌激下丘脑室旁核的镇痛作用

This study was undertaken to evaluate the analgesic effect of paraventricular nucleus (PVN) stimulation with tail stimulation-vocalization test. The mechanism of this analgesia was analysed with nuclear lesion and microinjection technique. The main results were as follows: (1) Electrical stimulation of the PVN could significantly enhance the pain threshold and increase the content of AVP in brainstem measured by radioimmunoassay. (2) Solitary tract nucleus (STN) lesion could eliminate the analgesic effect induced by PVN stimulation. (3) Intranuclear microinjection of AVP-antagonist and AVP-antiserum into the STN could block the analgesic effect of PVN stimulation. (4) Intranuclear microinjection of AVP into the STN could mimick the analgesic effect similar to that of PVN stimulation. These results suggest that electrical stimulation of the PVN could produce an analgesic effect. This effect might be mediated by the activation of VP-ergic neurons in PVN and upon releasing VP from the descending fibers, the activities of neurons in the STN are influenced.     

刺激大鼠大脑脚影响脊髓伤害感受性传递的下行途径

在麻醉大鼠用部分切割脊髓的方法分析了刺激大脑脚影响脊髓背角伤害感受性神经元的下委途径。刺激ＣＰ对背角神经元伤害感受性反应（Ｃ－反应）的影响以抑制为,部分（３０．７％）神经元在抑制作用产生之前先被兴历,抑制作用主要是通过背索或背外侧索实现的,然而在多数神经元是两者共同作用的结果,其中ＤＬＦ的作用似乎更为重要。兴历作用则是通过ＤＦ实现的。由于大鼠的皮质脊髓束位于ＤＦ中,以上结果提示大脑皮层不仅可直接通     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fospositive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fos-positive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

Morphology of lumbar-projecting lateral vestibulospinal neurons in the brainstem and cervical spinal cord in the squirrel monkey

The lateral vestibulospinal tract (LVST) is one of the major descending pathways controlling the extensor musculature of the body. To determine whether individual LVST neurons terminating in the lumbosacral spinal segments issue collaterals more rostrally to exert an influence of the cervical ventral horn intracellular recording and biocytin labeling techniques were used in the squirrel monkey. Only neurons monosynaptically related to the 8th nerve and antidromically identified to project below T12 were selected for study. The axon course through the brainstem and cervical spinal cord was examined in 37 LVST neurons. The average distance of recovered axon was 17.3 mm (4.5-31.7 mm). None could be antidromically activated from shocks applied to the rostral medial longitudinal fasciculus near the 3rd nuclei; and no collaterals were observed in the brainstem. Of the 37 neurons, only 1 axon issued a collateral to innervate the ventral horn, primarily in the region of the spinal accessory motoneurons; this single collateral provided a relatively minor input compared to that of LVST neurons terminating in the cervical cord. Thus, secondary, caudal-projecting LVST neurons represent a private, and mostly rapid, communication pathway between dorsal Deiters' nucleus and the motor circuits controlling the lower limbs and tail.     

Organization of the ferret lateral cervical nucleus and cervicothalamic tract

To elucidate the organization of the ferret spinocervicothalamic pathway (SCTP), we examined the lateral cervical nucleus (LCN) and the termination of the cervicothalamic tract (CTY) in this species. In thionin-stained sections, the ferret LCN appeared as an easily delineated column of cells in the dorsolateral funiculus from about mid-C3 to the rostral end of C1, with most cells located in the C1 and C2 segments. In transverse sections, the LCN was elongated along a dorsolateral to ventromedial axis and in the rostral half of C2 and caudal half of C1 continuous with the neck of the dorsal horn. The number of ferret LCN cells was estimated to 2,500-3,700, with an average of 3,340. Substance P-like immunoreactive fibers located preferentially in the ventromedial part of the LCN, whereas serotonin-like immunoreactive fibers were found throughout the nucleus. Anterograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and biotinylated dextran amine demonstrated that the ferret CTT terminates extensively in the peripheral parts of the ventral posterior lateral nucleus. Sparser termination was evident in the ventral posterior inferior nucleus, in the medial nucleus of the posterior complex, and in the medial part of the magnocellular medial geniculate nucleus. Thus, although the LCN is significantly smaller in ferrets than in cats and raccoons, the organization of the LCN and of the cervicothalamic tract is closely similar in the three species. These findings indicate a conserved general organization of the SCTP among carnivores.     

Organization of the ferret lateral cervical nucleus and cervicothalamic tract

To elucidate the organization of the ferret spinocervicothalamic pathway (SCTP), we examined the lateral cervical nucleus (LCN) and the termination of the cervicothalamic tract (CTT) in this species. In thionin-stained sections, the ferret LCN appeared as an easily delineated column of cells in the dorsolateral funiculus from about mid-C3 to the rostral end of C1, with most cells located in the C1 and C2 segments. In transverse sections, the LCN was elongated along a dorsolateral to ventromedial axis and in the rostral half of C2 and caudal half of C1 continuous with the neck of the dorsal horn. The number of ferret LCN cells was estimated to 2,500-3,700, with an average of 3,340. Substance P-like immunoreactive fibers located preferentially in the ventromedial part of the LCN, whereas serotonin-like immunoreactive fibers were found throughout the nucleus. Anterograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and biotinylated dextran amine demonstrated that the ferret CTT terminates extensively in the peripheral parts of the ventral posterior lateral nucleus. Sparser termination was evident in the ventral posterior inferior nucleus, in the medial nucleus of the posterior complex, and in the medial part of the magnocellular medial geniculate nucleus. Thus, although the LCN is significantly smaller in ferrets than in cats and raccoons, the organization of the LCN and of the cervicothalamic tract is closely similar in the three species. These findings indicate a conserved general organization of the SCTP among carnivores.     

Central representation of dental structures in the kitten, including projections to the mesencephalic trigeminal nucleus

Horseradish peroxidase (HRP) was injected into either a single maxillary or a single mandibular primary (deciduous) cuspid tooth of 8- to 10-week-old kittens. The large apex of the primary cuspid allowed for some leakage of the HRP from the pulpal chamber to the periodontal ligament (PDL). Thus, the injection procedure resulted in the application of HRP to the PDL as well as to the pulpal tissues. The transganglionic transport of HRP resulted in discrete terminal fields within the spinal trigeminal nucleus (STN) and the main sensory nucleus (MSN). These projections were clearly somatotopically organized within the STN, but less so within MSN. Within pars oralis (PO) and pars interpolaris (PI), mandibular cuspid dental structures (MdCDS) were represented in a dorsal position relative to the maxillary cuspid dental structures (MxCDS), whereas within pars caudalis (PC) and the adjacent reticular formation the somatotopic representation was not dorsoventral, but rather mediolateral, with the MdCDS represented more medially than the MxCDS. Areas of overlap between MxCDS and MdCDS were found within MSN and to a lesser degree within the superficial laminae of PC. In addition, the fiber pathway leading to labeled somata in the mesencephalic trigeminal (Mes V) nucleus was clearly identified. The majority of the fibers traced to the Mes V nucleus exited the spinal trigeminal tract at the level of the transition from PO to the MSN and traversed the nuclear region in a position dorsal to and separate from the trigeminal motor tract. As in STN, fibers within the caudal Mes V tract appeared to be somatotopically organized, with the fibers from the MdCDS generally more dorsal than the ones from the MxCDS. Labeled fibers, some with terminal arbors, were also identified in close association with the trigeminal motor tract. The findings show a complex pattern of central representation in the immature feline central nervous system for deciduous dental structures.     

Identification of penile inputs to the rat gracile nucleus

Neurons in the medullary reticular formation (MRF) of the rat receive a vast array of urogenital inputs. Using select acute and chronic spinal cord lesions to identify the location of the ascending neural circuitries providing either direct or indirect inputs to MRF from the penis, our previous studies demonstrated that the dorsal columns and dorsal half of the lateral funiculus convey low- and high-threshold inputs, respectively. In the present study, the gracile nucleus was targeted as one of the likely sources of low-threshold information from the penis to MRF. Both electrophysiological recordings and neuroanatomical tracing [injection of cholera toxin B subunit (CTB) into a dorsal nerve of the penis] were used. After discrimination of a single neuron responding to penile stimulation, testing for somatovisceral convergence was done (mechanical stimulation of the distal colon and the skin over the entire hindquarters). In 12 rats, a limited number of neurons (43 in total) responded to penile stimulation. Many of these neurons also responded to scrotal stimulation (53.5%, dorsal and/or ventral scrotum) and/or prepuce stimulation (46.5%). Histological reconstruction of the electrode tracks showed that the majority of neurons responding to penile stimulation were located ventrally within the medial one-third of the gracile nucleus surrounding obex. This location corresponded to sparse innervation by CTB-immunoreactive primary afferent terminals. These results indicate that neurons in the gracile nucleus are likely part of the pathway that provides low-threshold penile inputs to MRF, a region known to play an important role in mating processes.     

Speaking out of turn: a role for silent synapses in pain

Severe tissue or nerve injury can result in a chronic and inappropriate sensation of pain, mediated in part by the sensitization of spinal dorsal horn neurons to input from primary afferent fibers. Synaptic transmission at primary afferent synapses is mainly glutamatergic. Although a functioning excitatory synapse contains both alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsynaptic membrane, recent evidence suggests that dorsal horn neurons contain some "silent" synapses, which exhibit purely NMDA receptor-mediated evoked postsynaptic currents and do not conduct signals at resting membrane potential. Serotonin, which is released onto dorsal horn neurons by descending fibers from the rostroventral medulla, potentiates sensory transmission by activating silent synapses on those neurons, i.e., by recruiting functional AMPA receptors to the postsynaptic membrane. This phenomenon may contribute to the hyperexcitability of dorsal horn neurons seen in chronic pain conditions.     

Responses of spinohypothalamic tract neurons in the thoracic spinal cord of rats to somatic stimuli and to graded distention of the bile duct

Anatomical studies indicate that a relatively large percentage of spinohypothalamic tract (SHT) neurons are located within thoracic spinal segments. The aim of this study was to characterize the responses of SHT neurons in these segments of rats to innocuous and noxious stimulation of the skin and of a visceral structure, the bile duct. In addition, we attempted to determine the trajectories of the axons of the examined neurons within the diencephalon and brainstem. Fifty-three SHT neurons were recorded within segments T8-T13 in urethane anesthetized rats. Each cell was antidromically activated using current pulses < or = 30 microA delivered from the tip of an electrode located within the contralateral hypothalamus. The recording points were located in the superficial dorsal horn (9) and deep dorsal horn (44). All examined SHT neurons had receptive fields on the posterior thorax and anterior and ventral abdomen of the ipsilateral side. Ninety percent of the 41 SHT neurons responded exclusively (13) or preferentially (24) to noxious cutaneous stimuli. Thirteen of 27 (48%) examined units were activated by forceful distention of the bile duct. Response thresholds ranged from 30 to 40 mmHg. Responses incremented as pressures were increased to 50-80 mmHg. The axons of 22 of 28 (79%) examined SHT neurons appeared to cross the midline within the hypothalamus and terminate in the ipsilateral hypothalamus, thalamus or midbrain. The results indicate that SHT neurons in thoracic spinal cord of rats are capable of conveying somatic and visceral nociceptive information from the bile duct directly to targets at various levels of the brain bilaterally.     

Fos Protein Expression in Sacral Spinal Cord in Relation to Early Phase of Cauda Equina Syndrome in Dogs

1. The aim of the present study is to map the incipient phase of Fos expression in the sacral spinal cord neuronal pools of multiple cauda equina constrictions canine model.2. Fos-positive neurons were found bilaterally in the lateral portion of superficial dorsal horn layers (Laminae I–III) and along the lateral edge of the dorsal horn accompanied by the lateral collateral pathway, fibers of Lissauer's tract, terminating at the sacral parasympathetic nucleus. Similarly, high Fos expression was detected in the ventral portion of the dorsal sacral commissure and in the dorsomedial portion of the anterior horns at S₁–S₃ segment level. Finally, a clearly expressed Fos-positivity was disclosed bilaterally in the neuropil of the nucleus Y in the anterior horn.3. Data from the present study show that continuous stimulation of the central fibers of sacral dorsal root ganglia neurons, i.e., fibers of sacral primary afferents, unlike those using various stimulations of the peripheral fibres offers an unusual pattern of Fos-like immunoreactivity.     

会阴部皮肤和盆腔内脏的伤害感受性信息在猫骶髓后连合核神经元的汇聚

在戊巴比妥钠麻醉的猫上,用玻璃微电极细胞外记录的方法,观察了躯体和内脏的伤害性刺激对骶髓后连合核神经元活动的影响。结果表明,所有接受盆神经内Ａδ纤维传入的神经元皆为特异性伤害感受或广动力范围神经元－它们可被包括会阴部皮肤的躯体感受野的机械性及强电刺激诱发。上述结果提示,Ａδ纤维可能在盆腔内脏的伤害感受性传递中起重要作用。     

刺激中缝背核对大鼠脊髓背角神经元伤害性反应的影响及其传出途径的分析

大量资料表明,中缝背核(DR)在痛觉调节中具有重要作用。本实验用电生理学方法研究DR在痛觉调制中的下行性抑制作用,主要观察刺激DR对清醒制动大鼠脊髓背角神经元伤害性放电的影响。其主要结果是:①刺激DR或电针可以抑制脊髓背角神经元的伤害性反应,吗啡可加强这种抑制效应;②损毁中缝大核(NRM)、纳洛酮、麦角酰二乙胺(LSD)、赛庚啶及对氯苯丙氨酸(PCPA)均能部分阻断DR对脊髓背角神经元伤害性反应的抑制,实验结果表明:刺激DR抑制脊髓背角神经元的伤害性反应,部分是通过NRM间接控制背角神经元的伤害性传入;还有一部分是不通过NRM,可能是DR直接对脊髓背角伤害性信息的调制。在这种下行性抑制通路中有5-HT和阿片样物质的参与。     

Electrophysiological Study of Supraspinal Input and Spinal Output of Cat's Subnucleus Reticularis Dorsalis (SRD) Neurons

This work addressed the study of subnucleus reticularis dorsalis (SRD) neurons in relation to their supraspinal input and the spinal terminating sites of their descending axons. SRD extracellular unitary recordings from anesthetized cats aimed to specifically test, 1) the rostrocaudal segmental level reached by axons of spinally projecting (SPr) neurons collateralizing or not to or through the ipsilateral nucleus reticularis gigantocellularis (NRGc), 2) whether SPr fibers bifurcate to the thalamus, and 3) the effects exerted on SRD cells by electrically stimulating the locus coeruleus, the periaqueductal grey, the nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191 SPr fibers tested to cervical 2 (Ce2), thoracic 5 (Th5) and lumbar5 (Lu5) stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity of SPr fibers slowed in the more proximal segments and increased with terminating distance along the cord. None of the 110 axons tested sent collaterals to the thalamus; instead thalamic stimulation induced long-latency polysynaptic responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of the tested neurons (18/227). Antidromic and orthodromic spikes were elicited from the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic responses were observed following stimulation of the periaqueductal gray or mesencephalic locomotor region. The results suggest that information from pain-and-motor-related supraspinal structures converge on SRD cells that through SPr axons having conduction velocities tuned to their length may affect rostral and caudal spinal cord neurons at fixed delays, both directly and in parallel through different descending systems. The SRD will thus play a dual functional role by simultaneously regulating dorsal horn ascending noxious information and pain-related motor responses.     

Differential localization of neuronal nitric oxide synthase immunoreactivity and NADPH-diaphorase activity in the cat spinal cord

The distributions of neuronal nitric oxide synthase immunoreactivity (NOS-IR) and NADPH-diaphorase (NADPH-d) activity were compared in the cat spinal cord. NOS-IR in neurons around the central canal, in superficial laminae (I and II) of the dorsal horn, in the dorsal commissure, and in fibers in the superficial dorsal horn was observed at all levels of the spinal cord. In these regions, NOS-IR paralleled NADPH-d activity. The sympathetic autonomic nucleus in the rostral lumbar and thoracic segments exhibited prominent NOS-IR and NADPH-d activity, whereas the parasympathetic nucleus in the sacral segments did not exhibit NOS-IR or NADPH-d activity. Within the region of the sympathetic autonomic nucleus, fewer NOS-IR cells were identified compared with NADPH-d cells. The most prominent NADPH-d activity in the sacral segments occurred in fibers within and extending from Lissauer's tract in laminae I and V along the lateral edge of the dorsal horn to the region of the sacral parasympathetic nucleus. These afferent projections did not exhibit NOS-IR; however, NOS-IR and NADPH-d activity were demonstrated in dorsal root ganglion cells (L7-S2). The results of this study demonstrate that NADPH-d activity is not always a specific histochemical marker for NO-containing neural structures.     

Central Representation of Dental Structures in the Kitten,Including Projections to the Mesencephalic Trigeminal Nucleus

Horseradish peroxidase (HRP) was injected into either a single maxillary or a single mandibular primary (deciduous) cuspid tooth of 8- to 10-week-old kittens. The large apex of the primary cuspid allowed for some leakage of the HRP from the pulpal chamber to the periodontal ligament (PDL). Thus, the injection procedure resulted in the application of HRP to the PDL as well as to the pulpal tissues. The transganglionic transport of HRP resulted in discrete terminal fields within the spinal trigeminal nucleus (STN) and the main sensory nucleus (MSN). These projections were clearly somatotopically organized within the STN, but less so within MSN. Within pars oralis (PO) and pars interpolaris (PI), mandibular cuspid dental structures (MdCDS) were represented in a dorsal position relative to the maxillary cuspid dental structures (MxCDS), whereas within pars caudalis (PC) and the adjacent reticular formation the somatotopic representation was not dorsoventral, but rather mediolateral, with the MdCDS represented more medially than the MxCDS. Areas of overlap between MxCDS and MdCDS were found within MSN and to a lesser degree within the superficial laminae of PC. In addition, the fiber pathway leading to labeled somata in the mesencephalic trigeminal (Mes V) nucleus was clearly identified. The majority of the fibers traced to the Mes V nucleus exited the spinal trigeminal tract at the level of the transition from PO to the MSN and traversed the nuclear region in a position dorsal to and separate from the trigeminal motor tract. As in STN, fibers within the caudal Mes V tract appeared to be somatotopically organized, with the fibers from the MdCDS generally more dorsal than the ones from the MxCDS. Labeled fibers, some with terminal arbors, were also identified in close association with the trigeminal motor tract. The findings show a complex pattern of central representation in the immature feline central nervous system for deciduous dental structures.     

大鼠中脑、内脏和躯体传入在旁巨细胞外侧核神经元的聚合

用细胞外记录的方法观察大鼠巨细胞旁外侧核（ＰＧＬ）对刺激中脑导水管周围背侧部（ｄＰＡＧ）及腹外侧部（ｖＰＡＧ）、腓深神经（ＤＰＮ）、正中神经（ＭＮ）和内脏大神经（ＧＳＰＬ）的反应。这些神经元不仅对某一处刺激部位起反应,而且倾向于对其它任一刺激部位也起反应。８９％（７３／８２）的神经元接受两处或两处以上来源的汇聚投射。６０％（２１／３５）的神经元由于具有压力敏感性,并且其下行投射到脊髓的轴突具有慢的     

脊髓背角痛觉传递和调制的一些化学解剖学观察

本实验研究了脊髓背角内Ｃ纤维末梢的分布和突触学特征及其一些神经递质化学构筑;定量观察了急性痛引起背角的递质变化;显示了初级传入Ｃ纤维,抑制性中间神经元和背角伤害性感受神经元三者之间的突触关系,并探讨它们在痛觉信息传递和调制中的作用。     

Cortical influences on neurons of the lateral reticular nucleus responding to noxious stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.