孤束核内儿茶酚胺能投射神经元接受面口部躯体伤害性和内脏传入信息汇聚的研究
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摘要
孤束核(NTS)是位于延髓背内侧的纵行核团,是内脏传入的主要投射区。NTS内的神经元可经Ⅶ、Ⅸ、Ⅹ对颅神经接受头颈和胸腹腔大部分内脏的初级传入信息。NTS被划分为多个亚核,不同亚核的功能不尽相同。其吻侧1/3与味觉传入相关,中尾段的腹外侧和中间内侧亚核与呼吸相关,中尾段的背内侧、胶质、小细胞、内侧和连合亚核与胃肠道及心血管的调节有关。NTS已被广泛认为是中枢和外周自律活动调节的起点。除内脏初级传入外,NTS也接受由脊髓背角Ⅰ层神经元中继的躯体伤害性信息。还可经三叉神经的分支接受头面部躯体传入信息。临床研究发现高强度面口部穴位的电针对躯体深层组织的刺激可影响内脏活动,而刺激迷走神经则能抑制牙髓神经炎性痛引起的二腹肌反射。提示作为迷走神经的主要中枢投射区,NTS可能在躯体—内脏反射通路中发挥重要的作用。Imbe.H等以完全弗氏佐剂(CFA)刺激大鼠的咬肌后,观察到NTS中大量表达FOS蛋白,而将注射侧的迷走神经切断后,FOS蛋白的表达量显著降低,说明对面口部深层组织的炎性刺激可诱发NTS神经元的活动,而且此种效应与迷走神经传递的内脏信息密切相关。
NTS内含有多种神经活性物质。在其内侧、连合及中间内侧亚核中分
The longitudinal nucleus of the solitary tract (NTS) is mainly located in the dorsomedial part of the medulla oblongata. NTS is a major site of primary termination for many visceral afferents. It receives visceral afferent from most organs in the neck, chest and abdomen through the VIIth, IXth, and Xth cranial nerves. The NTS can be divided into different subnuclei that are associated with different functions. The rostral part of NTS receives the special visceral, gustatory afferents, while the ventrolateral and intermedial subnuclei of the mid-caudal part are associated with the respiratory control. The dorsomedial, parvocellular, medial and commissural subnuclei of the mid-caudal part are associated with the regulation of gastrointestinal and cardiovascular functions. The NTS is regarded as the initial regulatory point of peripheral and central nervous autonomic reflexes. Besides the visceral inputs, the NTS can receive projections from cells in lamina I of spinal cord that relaying peripheral somatic nociceptive information, it also receives somatic orofacial information through the branches of the trigeminal nerve. Clinical studies found that electrical acupuncture stimulating the orofacial acupuncture points could affect visceral activities. Vagal stimulation inhibits tooth pulp
nerve-evoked digastric reflexes. These data suggest that the NTS as a major site of primary termination for visceral afferents may make a significant contribution to somatovisceral signal processing. Imbe.H et al observed that FOS positive neurons existed in bilateral NTS after the complete Freund's adjuvant (CFA) injection into the masseter muscle, but unilateral vagotomy resulted in a selective reduction of inflammation-induced FOS protein expression at the NTS. These findings indicated that the inflammation of the masseter muscle, an injury of orofacial deep tissue, effects widespread change of the neuronal activities in NTS that depends in part on the integrity of the vagus afferents.The NTS is rich in neuroactive substances. The medial, commissural, and intermedial subnuclei contain catecholaminergic (CA) neurons belonging to the noradrenergic group A2 and adrenergic group C2. Tyrosine hydroxylase (TH) is the key and rate-limiting enzyme in the biosynthesis of CA, and is a special marker of the CA neurons. Up to now, it has drawn attention that the CA neurons in the medulla oblongata have an important effect in regulation of the visceral activation. Hypertensive haemorrhage and nociceptive stimulation to gastrointestinal have been shown to induce the expression of FOS protein in CA neurons of NTS. Further more, it has found by using electromicroscope that these neurons can make synapse with afferent inputs of the vagus. Since CA is a type of inhibitory neuroactive substance, the CA neurons of NTS could directly regulate the visceral afferent signals. Besides visceral inputs, these neurons also receive somatic orofacial nociceptive information. These studies indicted that the CA neurons of NTS might be involved in the regulation of somatovisceral reflex. The projection of the CA neurons is very extensive, with the lateral parabrachial nucleus (LPB) as the major projection
target. Anatomic studies have recognized that the LPB receives visceral information from NTS and somatic one from the spinal cord and medulla dorsal horn. Therefore, the parabrachial nucleus (PBN) is an important area to integrate the somatic and visceral afferent signals. Up to date, it is unclear whether CA neurons projecting to PBN in NTS could receive nociceptive information from somatic orofacial deep tissue, and whether nociceptive information from somatic orofacial deep tissue and visceral inputs carried by vagus nerve could converge onto the CA neurons projecting to PBN in NTS. If these questiones could be resolved, it will be very helpful to clearify the mechanism of convergence and regulation of somatic and visceral information in central nervous system.The present study use methods of retrograde and transganglionic tracing, formalin stimulating masseter muscle, combined with immunofluorescence histochemistry techniques, to address these questions through a series of experiments on Sprague-Dawley (SD) rat.In the first series of experiments, 2% fluoro-gold (FG) was unilaterally injected into the LPB for retrograde tracing and 2% formalin was administered into the ipsilateral masseter muscle, combined with immunofluorescence for the detection of FOS and TH in the rat. Under fluorescent microscope, it was shown that 3 kinds of single-labeled neurons (FG, TH, FOS), 3 kinds of double-labelad neurons (FG/TH, FOS/TH, FOS/FG) and FG/FOS/TH triple-labeled neurons were mainly located ipsilaterally in the commissural, medial, intermedial and ventral subnucleus of NTS. The percentage of neurons, which receive stimulating information from masseter muscle and project to LPB, accounted for 26.4% of the ipsilateral FG retrograde-labeled neurons. The percentage of TH positive neurons, which receive orofacial stimulating
information and project to LPB, were 23.7% and 8.4% of the ipsilateral total numbers of TH and FG single-labeled neurons, respectively. In addition, 10% tetramethyl rhodamine (TMR) instead of FG was unilaterally injected into the LPB. Under laser scanning confocal microscope (LSCM), the result is consistent with above data. These results indicate that some of catecholaminergic neurons of NTS might receive nociceptive inputs from somatic orofacial deep tissue and transmit this information to the lateral parabrachial nucleus.In the second series, 10% TMR was unilaterally injected into LPB for retrograde labeling, 10% biotinylated dextran amine (BDA) was ipsilaterally injected into the cervical trunk of vagus nerve for transganglionic tracing , and ipsilateral injection of 2% formalin into the masseter muscle , immunofluorescence was made to detect TH and FOS. Under LSCM, it was shown that ? part of TH positive neurons expressed FOS protein, and formed close apposition with immunolabeled terminals from vagus afferents, ? in NTS, part of the projecting neurons to LPB expressed FOS protein, and formed close apposition with vagus primary inputs. These results suggest that somatic nociceptive message from orofacial deep tissue and visceral message carried by vagus nerve might converge onto some CA neurons in NTS; In NTS, some neurons projecting to LPB might receive visceral afferents and nociceptive information from orofacial deep tissue, and part of that are CA neurons.Taken together, the present results indicate that nociceptive information from orofacial deep tissue and visceral message carried by vagus nerve might converge onto CA neurons in NTS. As an inhibitory neurotransmitter, CA might regulate the two types of information, and transmit integrated signals to
NTS内含有多种神经活性物质。在其内侧、连合及中间内侧亚核中分
The longitudinal nucleus of the solitary tract (NTS) is mainly located in the dorsomedial part of the medulla oblongata. NTS is a major site of primary termination for many visceral afferents. It receives visceral afferent from most organs in the neck, chest and abdomen through the VIIth, IXth, and Xth cranial nerves. The NTS can be divided into different subnuclei that are associated with different functions. The rostral part of NTS receives the special visceral, gustatory afferents, while the ventrolateral and intermedial subnuclei of the mid-caudal part are associated with the respiratory control. The dorsomedial, parvocellular, medial and commissural subnuclei of the mid-caudal part are associated with the regulation of gastrointestinal and cardiovascular functions. The NTS is regarded as the initial regulatory point of peripheral and central nervous autonomic reflexes. Besides the visceral inputs, the NTS can receive projections from cells in lamina I of spinal cord that relaying peripheral somatic nociceptive information, it also receives somatic orofacial information through the branches of the trigeminal nerve. Clinical studies found that electrical acupuncture stimulating the orofacial acupuncture points could affect visceral activities. Vagal stimulation inhibits tooth pulp
nerve-evoked digastric reflexes. These data suggest that the NTS as a major site of primary termination for visceral afferents may make a significant contribution to somatovisceral signal processing. Imbe.H et al observed that FOS positive neurons existed in bilateral NTS after the complete Freund's adjuvant (CFA) injection into the masseter muscle, but unilateral vagotomy resulted in a selective reduction of inflammation-induced FOS protein expression at the NTS. These findings indicated that the inflammation of the masseter muscle, an injury of orofacial deep tissue, effects widespread change of the neuronal activities in NTS that depends in part on the integrity of the vagus afferents.The NTS is rich in neuroactive substances. The medial, commissural, and intermedial subnuclei contain catecholaminergic (CA) neurons belonging to the noradrenergic group A2 and adrenergic group C2. Tyrosine hydroxylase (TH) is the key and rate-limiting enzyme in the biosynthesis of CA, and is a special marker of the CA neurons. Up to now, it has drawn attention that the CA neurons in the medulla oblongata have an important effect in regulation of the visceral activation. Hypertensive haemorrhage and nociceptive stimulation to gastrointestinal have been shown to induce the expression of FOS protein in CA neurons of NTS. Further more, it has found by using electromicroscope that these neurons can make synapse with afferent inputs of the vagus. Since CA is a type of inhibitory neuroactive substance, the CA neurons of NTS could directly regulate the visceral afferent signals. Besides visceral inputs, these neurons also receive somatic orofacial nociceptive information. These studies indicted that the CA neurons of NTS might be involved in the regulation of somatovisceral reflex. The projection of the CA neurons is very extensive, with the lateral parabrachial nucleus (LPB) as the major projection
target. Anatomic studies have recognized that the LPB receives visceral information from NTS and somatic one from the spinal cord and medulla dorsal horn. Therefore, the parabrachial nucleus (PBN) is an important area to integrate the somatic and visceral afferent signals. Up to date, it is unclear whether CA neurons projecting to PBN in NTS could receive nociceptive information from somatic orofacial deep tissue, and whether nociceptive information from somatic orofacial deep tissue and visceral inputs carried by vagus nerve could converge onto the CA neurons projecting to PBN in NTS. If these questiones could be resolved, it will be very helpful to clearify the mechanism of convergence and regulation of somatic and visceral information in central nervous system.The present study use methods of retrograde and transganglionic tracing, formalin stimulating masseter muscle, combined with immunofluorescence histochemistry techniques, to address these questions through a series of experiments on Sprague-Dawley (SD) rat.In the first series of experiments, 2% fluoro-gold (FG) was unilaterally injected into the LPB for retrograde tracing and 2% formalin was administered into the ipsilateral masseter muscle, combined with immunofluorescence for the detection of FOS and TH in the rat. Under fluorescent microscope, it was shown that 3 kinds of single-labeled neurons (FG, TH, FOS), 3 kinds of double-labelad neurons (FG/TH, FOS/TH, FOS/FG) and FG/FOS/TH triple-labeled neurons were mainly located ipsilaterally in the commissural, medial, intermedial and ventral subnucleus of NTS. The percentage of neurons, which receive stimulating information from masseter muscle and project to LPB, accounted for 26.4% of the ipsilateral FG retrograde-labeled neurons. The percentage of TH positive neurons, which receive orofacial stimulating
information and project to LPB, were 23.7% and 8.4% of the ipsilateral total numbers of TH and FG single-labeled neurons, respectively. In addition, 10% tetramethyl rhodamine (TMR) instead of FG was unilaterally injected into the LPB. Under laser scanning confocal microscope (LSCM), the result is consistent with above data. These results indicate that some of catecholaminergic neurons of NTS might receive nociceptive inputs from somatic orofacial deep tissue and transmit this information to the lateral parabrachial nucleus.In the second series, 10% TMR was unilaterally injected into LPB for retrograde labeling, 10% biotinylated dextran amine (BDA) was ipsilaterally injected into the cervical trunk of vagus nerve for transganglionic tracing , and ipsilateral injection of 2% formalin into the masseter muscle , immunofluorescence was made to detect TH and FOS. Under LSCM, it was shown that ? part of TH positive neurons expressed FOS protein, and formed close apposition with immunolabeled terminals from vagus afferents, ? in NTS, part of the projecting neurons to LPB expressed FOS protein, and formed close apposition with vagus primary inputs. These results suggest that somatic nociceptive message from orofacial deep tissue and visceral message carried by vagus nerve might converge onto some CA neurons in NTS; In NTS, some neurons projecting to LPB might receive visceral afferents and nociceptive information from orofacial deep tissue, and part of that are CA neurons.Taken together, the present results indicate that nociceptive information from orofacial deep tissue and visceral message carried by vagus nerve might converge onto CA neurons in NTS. As an inhibitory neurotransmitter, CA might regulate the two types of information, and transmit integrated signals to
引文
[1] Kalia M, Mesulam M-M. Brain stem projection of sensory and motor components of the vagus complex in the cat. Ⅰ. The cervical vagus and nodose ganglion. J Comp Neurol, 1980; 193:453-465
[2] Kalia M, Mesulam M-M. Brain stem projection of sensory and motor components of the vagus complex in the cat. Ⅱ. laryngeal, tracheobronchial, pulmonary, cardiac and gastrointestinal branches. J Comp Neurol, 1980; 193: 467-508
[3] Zigmond RE, Schwarzschild MA, Rittenhouse AR. Acute regulation of tyrosinef hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Annu Rev Neurosci, 1989; 12: 415-461
[4] Moore RY, Bloom FE. Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci, 1979; 2: 113-168
[5] Takeshige C, Sato T, Mera T et al. Descending pain inhibitory system involved in acupuncture analgesia. Brain Res Bull, 1992; 29:617-634
[6] 党小荣,张文斌.大鼠孤束核内传递内脏伤害性信息的儿茶酚胺能神经元向臂旁核的投射.神经解剖学杂志,2001:17:235-238
[7] Norgren R. Projections from the nucleus of the solitary tract in the rat. Neuroscience, 1978; 3: 207-218
[8] Cechetto DF, Calaresu FR. Central pathways relaying cardiovascular afferent information to amygdala. Am J Physiol, 1985; 248: 38-45
[9] Rodella L, Rezzani R, Gioia M et al. Expression of Fos immunoreactivity in the rat supraspinal regions following noxious visceral stimulation. Brain Res Bull, 1998; 47: 357-366
[10] Han F, Zhang YF, Li YQ. Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation: an immunohistochemical study. World J Gastroenterol, 2003; 9:1045-1050
[11] Zhou Q, Imbe H, Dubner R et al. Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats: Implications for persistent orofacial pain. J CompNeurol, 1999: 412:276-291
[12] Imbe H, Dubner R, Ren K. Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone : contribution of somatosensory-vagal-adrenal integration. Brain Res, 1999: 845:165-175
[13] 张文斌,李继硕,李惠民.三叉神经初级传入纤维与孤束核的联系—HRP跨神经节追踪研究.神经解剖学杂志,1990;6:97-106
[14] Cunningham ET Jr, Sawchenko PE. Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol, 1988: 274:60-76
[15] Petrov T, Krukoff TL, Jhamandas JH. Branching projections of catecholaminergic brainstem neurons to the paraventricular hypothalamic nucleus and the central nucleus of the amygdala in the rat. Brain Res, 1993; 609:81-92
[16] Smith OA, De Vito JL. Central neural integration for the control of autonomic responses associated with emotion. Annu Rev Neurosci, 1984; 7: 43-65
[17] Nishimori T, Sear M, Suemune S et al. The distribution of muscle primary afferents from the masseter nerve to the trigeminal sensory nuclei. Brain Res, 1986; 372:375-381
[18] Hu JW, Sessle BJ, Raboisson P et al. Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brain-stem neurons. Pain, 1992: 48:53-60
[19] Barraco IRA. Nucleus of the solitary tract. Boca Raton: CRC Press, 1994
[2] Kalia M, Mesulam M-M. Brain stem projection of sensory and motor components of the vagus complex in the cat. Ⅱ. laryngeal, tracheobronchial, pulmonary, cardiac and gastrointestinal branches. J Comp Neurol, 1980; 193: 467-508
[3] Zigmond RE, Schwarzschild MA, Rittenhouse AR. Acute regulation of tyrosinef hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Annu Rev Neurosci, 1989; 12: 415-461
[4] Moore RY, Bloom FE. Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci, 1979; 2: 113-168
[5] Takeshige C, Sato T, Mera T et al. Descending pain inhibitory system involved in acupuncture analgesia. Brain Res Bull, 1992; 29:617-634
[6] 党小荣,张文斌.大鼠孤束核内传递内脏伤害性信息的儿茶酚胺能神经元向臂旁核的投射.神经解剖学杂志,2001:17:235-238
[7] Norgren R. Projections from the nucleus of the solitary tract in the rat. Neuroscience, 1978; 3: 207-218
[8] Cechetto DF, Calaresu FR. Central pathways relaying cardiovascular afferent information to amygdala. Am J Physiol, 1985; 248: 38-45
[9] Rodella L, Rezzani R, Gioia M et al. Expression of Fos immunoreactivity in the rat supraspinal regions following noxious visceral stimulation. Brain Res Bull, 1998; 47: 357-366
[10] Han F, Zhang YF, Li YQ. Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation: an immunohistochemical study. World J Gastroenterol, 2003; 9:1045-1050
[11] Zhou Q, Imbe H, Dubner R et al. Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats: Implications for persistent orofacial pain. J CompNeurol, 1999: 412:276-291
[12] Imbe H, Dubner R, Ren K. Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone : contribution of somatosensory-vagal-adrenal integration. Brain Res, 1999: 845:165-175
[13] 张文斌,李继硕,李惠民.三叉神经初级传入纤维与孤束核的联系—HRP跨神经节追踪研究.神经解剖学杂志,1990;6:97-106
[14] Cunningham ET Jr, Sawchenko PE. Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol, 1988: 274:60-76
[15] Petrov T, Krukoff TL, Jhamandas JH. Branching projections of catecholaminergic brainstem neurons to the paraventricular hypothalamic nucleus and the central nucleus of the amygdala in the rat. Brain Res, 1993; 609:81-92
[16] Smith OA, De Vito JL. Central neural integration for the control of autonomic responses associated with emotion. Annu Rev Neurosci, 1984; 7: 43-65
[17] Nishimori T, Sear M, Suemune S et al. The distribution of muscle primary afferents from the masseter nerve to the trigeminal sensory nuclei. Brain Res, 1986; 372:375-381
[18] Hu JW, Sessle BJ, Raboisson P et al. Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brain-stem neurons. Pain, 1992: 48:53-60
[19] Barraco IRA. Nucleus of the solitary tract. Boca Raton: CRC Press, 1994