共查询到20条相似文献，搜索用时 78 毫秒
1.
Abrahamsen B Zhao J Asante CO Cendan CM Marsh S Martinez-Barbera JP Nassar MA Dickenson AH Wood JN 《Science (New York, N.Y.)》2008,321(5889):702-705
Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing. 相似文献
2.
Neuronal plasticity: increasing the gain in pain 总被引：1，自引：0，他引：1
We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity. 相似文献
3.
Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex
Li XY Ko HG Chen T Descalzi G Koga K Wang H Kim SS Shang Y Kwak C Park SW Shim J Lee K Collingridge GL Kaang BK Zhuo M 《Science (New York, N.Y.)》2010,330(6009):1400-1404
Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMζ in the ACC acts to maintain neuropathic pain. PKMζ could thus be a new therapeutic target for treating chronic pain. 相似文献
4.
Boucher TJ Okuse K Bennett DL Munson JB Wood JN McMahon SB 《Science (New York, N.Y.)》2000,290(5489):124-127
Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states. 相似文献
5.
Harvey RJ Depner UB Wässle H Ahmadi S Heindl C Reinold H Smart TG Harvey K Schütz B Abo-Salem OM Zimmer A Poisbeau P Welzl H Wolfer DP Betz H Zeilhofer HU Müller U 《Science (New York, N.Y.)》2004,304(5672):884-887
Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR alpha3 not only lack the inhibition of glycinergic neurotransmission by PGE2 seen in wild-type mice but also show a reduction in pain sensitization induced by spinal PGE2 injection or peripheral inflammation. Thus, GlyR alpha3 may provide a previously unrecognized molecular target in pain therapy. 相似文献
6.
Electrical activity plays a critical role in shaping the structure and function of synaptic connections in the nervous system. In Xenopus nerve-muscle cultures, a brief burst of action potentials in the presynaptic neuron induced a persistent potentiation of neuromuscular synapses that exhibit immature synaptic functions. Induction of potentiation required an elevation of postsynaptic Ca2+ and expression of potentiation appeared to involve an increased probability of transmitter secretion from the presynaptic nerve terminal. Thus, activity-dependent persistent synaptic enhancement may reflect properties characteristic of immature synaptic connections, and bursting activity in developing spinal neurons may promote functional maturation of the neuromuscular synapse. 相似文献
7.
Nociceptive neuronal circuits are formed during embryonic and postnatal times when painful stimuli are normally absent or limited. Today, medical procedures for neonates with health risks can involve tissue injury and pain for which the long-term effects are unknown. To investigate the impact of neonatal tissue injury and pain on development of nociceptive neuronal circuitry, we used an animal model of persistent hind paw peripheral inflammation. We found that, as adults, these animals exhibited spinal neuronal circuits with increased input and segmental changes in nociceptive primary afferent axons and altered responses to sensory stimulation. 相似文献
8.
α6/α3β4烟碱型乙酰胆碱受体（α6β4* nAChRs,*代表其他亚基）主要分布于大脑海马区、外周神经节和人源肾上腺嗜铬细胞等,与神经性疼痛和炎症反应、情绪等生理疾病密切相关。本研究拟对大鼠α6/α3β4 nAChR在非洲爪蟾（Xenopus laevis）卵母细胞膜上进行重组表达,并利用双电极电压钳电生理学技术检测该重组受体的功能。在不同浓度的激动剂乙酰胆碱的刺激下,比较了α6/α3和β4亚基的不同配比形成的受体通道开放而产生的电流大小,并用其拮抗剂α?芋螺毒素TxID验证了该受体的敏感性。结果表明,亚基不同配比的α6/α3β4 nAChR均可在非洲爪蟾卵母细胞膜上成功表达,并具有较好的配体门控敏感性。 相似文献
9.
用HRP法对七只山羊的腓神经的来源及节段性分布规律进行追踪观察,结果如下: 1.腓神经感觉神经元胞体主要集中于L_6和S_1脊神经节内,其次位于S_2脊神经节内。其胞体多呈椭圆形和圆形,可分大、中、小三型,而以中型为主。 2.腓神经运动神经元胞体主要集中于L_6和S_1脊髓腹角,其次位于L_S脊髓腹角。胞体多呈星状或三角形。多数为较大的多极神经元,少数为小型多极神经元。 相似文献
10.
鸡腔上囊传出神经元的分布——用CB—HRP法研究 总被引：6，自引：0，他引：6
将CB—HRP注入鸡腔上囊壁内,支配腔上囊的神经元被标记。支配腔上囊的长轴突型交感节前神经元在胸7—腰荐3(简称T_7—LS_3)髓节的Terni氏柱内,主要位于LS_1—LS_2髓节。在LS_8—LS_(11)髓节中央管背侧和背外侧区有大量标记细胞,主要集中于LS_8髓节,这些标记细胞是支配腔上囊的副交感节前神经元,其轴突大部分行经同侧盆神经到达腔上囊,少数行经对侧的盆神经到达腔上囊。腔上囊的交感节后神经元位于T_6—L_(13)交感干神经节和肾上腺神经节,交感干的标记细胞集中位于LS_9—LS_(11)和LS_2—LS_3。副交感节后神经元位于盆神经和泄殖腔神经节内。在肠神经内有大量的标记细胞。 相似文献
11.
Ethanol neurotoxicity: effects on neurite formation and neurotrophic factor production in vitro 总被引：3，自引：0，他引：3
The effects of ethanol on chick embryo sensory and spinal cord neurons growing on one of several biological substrates (poly-D-lysine, laminin, or neuron-produced neurite-promoting materials) were examined. Ethanol inhibited process formation by the neurons in a dose-dependent manner and inhibited the production of neurotrophic factors. Neuronal attachment to the substrates, survival of attached neurons, and receptor interactions of sensory neurons with nerve growth factor were not influenced by ethanol. It appears that ethanol alters certain metabolic characteristics of developing neurons. 相似文献
12.
鸡腔上囊传入神经元的分布——HRP法研究 总被引：1，自引：0，他引：1
用CB—HRP法研究鸡腔上囊的感觉神经分布,结果表明:初级传入神经元位于T_6—LS_(13)脊神经节内,主要在LS_9—LS_(11)和LS_1—LS_2;初级传入神经元的中枢突在LS_8—LS_(12)髓节沿背角外侧缘延伸,止于中央管背测阳背外测区;部分初级传入神经元位于迷走神经结状节内。 相似文献
13.
J Y Kuwada 《Science (New York, N.Y.)》1986,233(4765):740-746
The mechanism that guides neuronal growth cones to their targets in vertebrate embryos has been difficult to study primarily because of the complexity and large number of neurons found in many vertebrate nervous systems. The spinal cord of a simple vertebrate, the fish embryo, is used to analyze pathfinding mechanisms. The early embryonic spinal cord consists of a relatively small number of identifiable neurons. From the beginning of axonal outgrowth the growth cones of these identified neurons extend along stereotyped and precise pathways in the spinal cord. Laser ablation experiments (i) support the hypothesis that early growth cones that pioneer specific spinal tracts appear to recognize cues on subsets of longitudinally arrayed neuroepithelial cells and (ii) demonstrate that later growth cones that selectively fasciculate in these spinal tracts appear to recognize cues on specific subsets of axons. 相似文献
14.
Synaptic connections in vitro: modulation of number and efficacy by electrical activity 总被引：1，自引：0，他引：1
The functional architecture of synaptic circuits is determined to a crucial degree by the patterns of electrical activity that occur during development. Studies with an in vitro preparation of mammalian sensory neurons projecting to ventral spinal cord neurons slow that electrical activity induces competitive processes that regulate synaptic efficacy so as to favor activated pathways over inactive convergent pathways. At the same time, electrical activity initiates noncompetitive processes that increase the number of axonal connections between these sensory and spinal cord neurons. 相似文献
15.
本实验采用HRP正中神经断端涂抹法,对五只山羊正中神经感觉纤维的节段性来源,进行了研究。结果表明:正中神经的感觉神经元主要集中于C_7、C_8和Th_1的脊神经节中,其次位于C_6、Th_2的脊神经节中。胞体形态具有多型性,并区分为大、中、小三型。其中以小型细胞为主。 相似文献
16.
Nerve growth factor attenuates neurotoxic effects of taxol on spinal cord-ganglion explants from fetal mice 总被引：3，自引：0，他引：3
Most neurons in organotypic cultures of dorsal root ganglia from 13-day-old fetal mice require high concentrations of nerve growth factor for survival during the first week after explanation. These nerve growth factor-enhanced sensory neurons mature and innervate the dorsal regions of attached spinal cord tissue even after the removal of exogenous growth factor after 4 days. In cultures exposed for 4 days to nerve growth factor and taxol (a plant alkaloid that promotes the assembly of microtubules) and returned to medium without growth factor, greater than 95 percent of the ganglionic neurons degenerated and the spinal cord tissues were reduced almost to monolayers. In contrast, when the recovery medium was supplemented with nerve growth factor, the ganglionic neurons and dorsal (but not ventral) cord tissue survived remarkably well. Dorsal cord neurons do not normally require an input from dorsal root ganglia for long-term maintenance in vitro, but during and after taxol exposure they become dependent for survival and recovery on the presence of neurite projections from nerve growth-factor-enhanced dorsal root ganglia. 相似文献
17.
Choline acetyltransferase activity is increased in combined cultures of spinal cord and muscle cells from mice 总被引：10，自引：0，他引：10
E L Giller B K Schrier A Shainberg H R Fisk P G Nelson 《Science (New York, N.Y.)》1973,182(112):588-589
The activity of choline acetyltransferase was more than tenfold greater in combined cultures of spinal cord and muscle cells than in cultures of spinal cord cells alone. This increase was associated with the formation of functional neuromuscular junctions in culture. Counts of silver-stained cells and determinations of other enzyme activities indicated that the increased choline acetyltransferase activity was not due to nonspecific neuronal survival but reflected greater activity in the surviving neurons. Hence, muscle had a marked, highly specific trophic effect on the cholinergic neurons that innervated it. 相似文献
18.
应用微电泳逆行追踪技术，分别向北京鸭，麻鸭，鹅、鸡、鸽和鹌鹑脊髓的颈、胸、腰段的一侧灰质中导入辣根过氧化物酶系统地研究了其孤束核至脊髓传导通路和细胞构筑。结果如下：在颈髓不同节段单侧灰质导入Ｈ ＲＰ后，６种家禽延髓的双侧孤束核内都出现了大量的标准细胞； 相似文献
19.
Some neurons of the rat central nervous system contain aromatic-L-amino-acid decarboxylase but not monoamines 总被引：7，自引：0，他引：7
C B Jaeger G Teitelman T H Joh V R Albert D H Park D J Reis 《Science (New York, N.Y.)》1983,219(4589):1233-1235
Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry. The majority of these neurons localized to area X of Rexed contact ependyma. Thus, spinal AADC neurons have the enzymatic capacity to catalyze directly the conversion of the amino acids tyrosine, tryptophan, or phenylalanine to their respective amines tyramine, tryptamine, or phenylethylamine. These amines normally present in the central nervous system may be of potential clinical significance as endogenous psychotomimetics. 相似文献