共查询到20条相似文献，搜索用时 46 毫秒
1.
Caterina MJ Leffler A Malmberg AB Martin WJ Trafton J Petersen-Zeitz KR Koltzenburg M Basbaum AI Julius D 《Science (New York, N.Y.)》2000,288(5464):306-313
The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia. 相似文献
2.
K L Casey 《Science (New York, N.Y.)》1971,173(991):77-80
In awake, unrestrained cats, bulboreticular neurons respond after electrical stimulation of cutaneous nerve with increasing discharge as stimulus intensity is raised to levels eliciting escape behavior. These cells discharge most vigorously to noxious natural somatic stimuli and are not driven by other sensory modalities. Electrical stimulation through the recording microelectrode also elicits escape, which further suggests bulboreticular participation in pain sensory mechanisms. 相似文献
3.
Moqrich A Hwang SW Earley TJ Petrus MJ Murray AN Spencer KS Andahazy M Story GM Patapoutian A 《Science (New York, N.Y.)》2005,307(5714):1468-1472
Environmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These "thermoTRPs" are activated at distinct temperature thresholds and are typically expressed in sensory neurons. TRPV3 is activated by heat (>33 degrees C) and, unlike most thermoTRPs, is expressed in mouse keratinocytes. We found that TRPV3 null mice have strong deficits in responses to innocuous and noxious heat but not in other sensory modalities; hence, TRPV3 has a specific role in thermosensation. The natural compound camphor, which modulates sensations of warmth in humans, proved to be a specific activator of TRPV3. Camphor activated cultured primary keratinocytes but not sensory neurons, and this activity was abolished in TRPV3 null mice. Therefore, heat-activated receptors in keratinocytes are important for mammalian thermosensation. 相似文献
4.
Emery EC Young GT Berrocoso EM Chen L McNaughton PA 《Science (New York, N.Y.)》2011,333(6048):1462-1466
The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the HCN ion channels, which generate an inward current, I(h), after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of I(h) and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Na(V)1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors. 相似文献
5.
Ventral posterior thalamic neurons differentially responsive to noxious stimulation of the awake monkey 总被引：1，自引：0，他引：1
Of 76 cutaneously activated neurons recorded from the ventral posterior thalamus of awake, behaving monkeys, nine were weakly excited by innocuous skin stimulation and responded maximally only when noxious mechanical cutaneous stimuli were delivered within small, contralateral receptive fields. These results show that neurons capable of encoding the spatial and temporal features of noxious stimuli are located in the ventral posterior thalamus of the awake primate. 相似文献
6.
Langford DJ Crager SE Shehzad Z Smith SB Sotocinal SG Levenstadt JS Chanda ML Levitin DJ Mogil JS 《Science (New York, N.Y.)》2006,312(5782):1967-1970
Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical noxious stimulus displayed increased pain behaviors with statistically greater co-occurrence, effects dependent on visual observation. When familiar mice were given noxious stimuli of different intensities, their pain behavior was influenced by their neighbor's status bidirectionally. Finally, observation of a cagemate in pain altered pain sensitivity of an entirely different modality, suggesting that nociceptive mechanisms in general are sensitized. 相似文献
7.
How do animals discriminate self-generated from external stimuli during behavior and prevent desensitization of their sensory pathways? A fundamental concept in neuroscience states that neural signals, termed corollary discharges or efference copies, are forwarded from motor to sensory areas. Neurons mediating these signals have proved difficult to identify. We show that a single, multisegmental interneuron is responsible for the pre- and postsynaptic inhibition of auditory neurons in singing crickets (Gryllus bimaculatus). Therefore, this neuron represents a corollary discharge interneuron that provides a neuronal basis for the central control of sensory responses. 相似文献
8.
Nichols ML Allen BJ Rogers SD Ghilardi JR Honore P Luger NM Finke MP Li J Lappi DA Simone DA Mantyh PW 《Science (New York, N.Y.)》1999,286(5444):1558-1561
Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain. 相似文献
9.
Pain responses to noxious thermal stimulation decreased in the acupunctured arm of subjects as compared to the arm not treated with acupuncture; this result suggested that effective analgesia had been induced. However, sensory decision theory analysis of the data revealed no difference in discriminability. This failure to find a sensory (physiological) change strongly suggests that analgesia had not been induced. The sole effect of acupuncture was to cause the subjects to raise their pain criterion in response to the expectation that acture works. 相似文献
10.
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
11.
Peier AM Reeve AJ Andersson DA Moqrich A Earley TJ Hergarden AC Story GM Colley S Hogenesch JB McIntyre P Bevan S Patapoutian A 《Science (New York, N.Y.)》2002,296(5575):2046-2049
Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons. 相似文献
12.
Zubieta JK Heitzeg MM Smith YR Bueller JA Xu K Xu Y Koeppe RA Stohler CS Goldman D 《Science (New York, N.Y.)》2003,299(5610):1240-1243
Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val158 homozygotes. The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli. 相似文献
13.
Sensory organs are composed of neurons, which convert environmental stimuli to electrical signals, and glia-like cells, whose functions are not well understood. To decipher glial roles in sensory organs, we ablated the sheath glial cell of the major sensory organ of Caenorhabditis elegans. We found that glia-ablated animals exhibit profound sensory deficits and that glia provide activities that affect neuronal morphology, behavior generation, and neuronal uptake of lipophilic dyes. To understand the molecular bases of these activities, we identified 298 genes whose messenger RNAs are glia-enriched. One gene, fig-1, encodes a labile protein with conserved thrombospondin TSP1 domains. FIG-1 protein functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. Our results suggest that glia are required for multiple aspects of sensory organ function. 相似文献
14.
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
15.
Larval development of the nematode Caenorhabditis elegans is controlled by the activities of four classes of chemosensory neurons. The choice between normal development and development into a specialized larval form called a dauer larva is regulated by competing environmental stimuli: food and a dauer pheromone. When the neuron classes ADF, ASG, ASI, and ASJ are killed, animals develop as dauer larvae regardless of environmental conditions. These neurons might sense food or dauer pheromone, or both, to initiate the specialized differentiation of many cell types that occurs during dauer formation. Entry into and exit from the dauer stage are primarily controlled by different chemosensory neurons. The analysis of mutants defective in dauer formation indicates that the chemosensory neurons are active in the absence of sensory inputs and that dauer pheromone inhibits the ability of these neurons to generate a signal necessary for normal development. 相似文献
16.
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
17.
The capsaicin receptor (TRPV1), a heat-activated ion channel of the pain pathway, is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis after phospholipase C activation. We identify a site within the C-terminal domain of TRPV1 that is required for PIP2-mediated inhibition of channel gating. Mutations that weaken PIP2-TRPV1 interaction reduce thresholds for chemical or thermal stimuli, whereas TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP2-activated potassium channels remain inhibited by PIP2. The PIP2-interaction domain therefore serves as a critical determinant of thermal threshold and dynamic sensitivity range, tuning TRPV1, and thus the sensory neuron, to appropriately detect heat under normal or pathophysiological conditions. 相似文献
18.
Gamma-aminobutyric acid antagonism in visual cortex: different effects on simple, complex, and hypercomplex neurons 总被引：4，自引：0，他引：4
Intravenous bicuculline was used to examine how removing gamma-aminobutyric acid-mediated inhibition affects the visual response properties of single cortical neurons. Simple neurons were depressed and complex neurons showed increase in the vigor and range of responses. Hypercomplex cells were no longer inhibited by elongated stimuli. The results are consistent with present evidence concerning the origin and distribution of inhibitory connections within the cortex. 相似文献
19.
所有背根节和迷走神经结状节出现大量P物质(SP)阳性胞体和纤维,小细胞占92％,大中型细胞占8％,仅有极少数生长抑素(SS)样神经胞体。大量含SP的纤维和终未见于颈上节和腹腔-前肠系膜神经节,但含SS的纤维和终末主要见于腹腔-前肠系膜神经节,颈上节甚少。交感节中无SP和SS阳性胞体。出现于交感神经节中的SP和SS纤维和终末,可能来自背根节初级感觉神经元的外周侧支或肠神经元。按照这个模式,SP和SS可通过不涉及中枢神经系统的外周短反射环路;去调节交感神经的反应。 相似文献
20.
Alarm pheromones (APs) are widely used throughout the plant and animal kingdoms. Species such as fish, insects, and mammals signal danger to conspecifics by releasing volatile alarm molecules. Thus far, neither the chemicals, their bodily source, nor the sensory system involved in their detection have been isolated or identified in mammals. We found that APs are recognized by the Grueneberg ganglion (GG), a recently discovered olfactory subsystem. We showed with electron microscopy that GG neurons bear primary cilia, with cell bodies ensheathed by glial cells. APs evoked calcium responses in GG neurons in vitro and induced freezing behavior in vivo, which completely disappeared when the GG degenerated after axotomy. We conclude that mice detect APs through the activation of olfactory GG neurons. 相似文献