刺激皮肤感受野对大鼠多觉型伤害性感受器诱发放电的影响

在大鼠尾部,重复压力刺激皮肤感受野,当间隔时间小于2min时,多觉型伤害性感受器的单位放电数随间隔时间的缩短而减少。压力与辐射热交叉刺激同一感受野,随后刺激的放电数也显著减少。皮下注射致痛剂引起持续性放电的背景上,分别向感受野施加按压、辐射热或电针刺激,随着放电增多后出现一个放电减少的过程。刺激支配尾部的交感神经则使减少的放电显著增多。结果表明,多觉型伤害性感受器受到刺激兴奋后有个感受性降低的过程。本文讨论了这一过程在按摩、针灸缓解痛机制中的可能作用。     

Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Na_v channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia.     

Few cultured rat primary sensory neurons express a tolbutamide-sensitive K+ current

The response of dorsal root ganglion (DRG) neurons to metabolic inhibition is known to involve calcium-activated K⁺ channels; in most neuronal types ATP-sensitive K⁺ channels (K_ATP) also contribute, but this is not yet established in the DRG. We have investigated the presence of a K_ATP current using whole-cell recordings from rat DRG neurons, classifying the neurons functionally by their "current signature" (Petruska et al, J Neurophysiol 84: 2365–2379, 2000). We clearly identified a K_ATP current in only 1 out of 62 neurons, probably a nociceptor. The current was activated by cyanide (2 mM NaCN) and was sensitive to 100 μM tolbutamide; the relation between reversal potential and external K⁺ concentration indicated it was a K⁺ current. In a further two neurons, cyanide activated a K⁺ current that was only partially blocked by tolbutamide, which may also be an atypical K_ATP current. We conclude that K_ATP channels are expressed in normal DRG, but in very few neurons and only in nociceptors.     

Whole-mount Imaging of Mouse Embryo Sensory Axon Projections

The visualization of full-length neuronal projections in embryos is essential to gain an understanding of how mammalian neuronal networks develop. Here we describe a method to label in situ a subset of dorsal root ganglion (DRG) axon projections to assess their phenotypic characteristics using several genetically manipulated mouse lines. The TrkA-positive neurons are nociceptor neurons, dedicated to the transmission of pain signals. We utilize a TrkA^taulacZ mouse line to label the trajectories of all TrkA-positive peripheral axons in the intact mouse embryo. We further breed the TrkA^taulacZ line onto a Bax null background, which essentially abolishes neuronal apoptosis, in order to assess growth-related questions independently of possible effects of genetic manipulations on neuronal survival. Subsequently, genetically modified mice of interest are bred with the TrkA^taulacZ/Bax null line and are then ready for study using the techniques described herein. This presentation includes detailed information on mouse breeding plans, genotyping at the time of dissection, tissue preparation, staining and clearing to allow for visualization of full-length axonal trajectories in whole-mount preparation.     

Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF

The nerve growth factor (NGF) precursor, proNGF, is implicated in various neuropathological states. ProNGF signals apoptosis by forming a complex with the receptors p75 and sortilin, however, it can also induce neurite growth, proposed to be mediated by the receptor of mature NGF, tyrosine kinase receptor A (TrkA). The way in which these dual effects occur in adult neurons is unclear. We investigated the neurotrophic effects of proNGF on peptidergic sensory neurons isolated from adult mouse dorsal root ganglia and found that proNGF stimulated neurite extension and branching, requiring p75, sortilin and TrkA. Neurite growth rarely occurred in sortilin-expressing neurons but was commonly observed in TrkA-positive, sortilin-negative neurons that associated closely with sortilin-positive glia. ProNGF was unable to induce local trophic effects at growth cones where sortilin-positive glia was absent. We propose that in adult sensory neurons the neurotrophic response to proNGF is mediated by NGF and TrkA, and that peri-somatic glia may participate in sortilin- and p-75 dependent cleavage of proNGF. The potential ability of local glial cells to provide a targeted supply of NGF may provide an important way to promote trophic (rather than apoptotic) outcomes under conditions where regeneration or sprouting is required.     

Coiled mechanoreceptors inAplysia revealed by sensorin immunofluorescence and confocal microscopy

Identified mechanosensory neurons ofAplysia are established model neurons for studies on learning and memory, and for examining responses to axonal injury. Although many characteristics of these sensory neurons have received intensive study, the nature of the peripheral mechanoreceptive endings remains unknown. Identification of a peptide, sensorin, specific inAplysia for mechanosensory neurons, led to the development of an antibody which proved useful in studying the peripheral morphology of these neurons. Immunostaining for sensorin in tail body wall revealed that sensorin is present in peripheral arborizations. Examination of sensorin-positive fibers in the periphery revealed that they terminate as coiled structures in the muscle layer of the body wall. These coiled structures (0.5 m diameter processes, 2–3 m across the coil, 60) m long) run parallel to muscle fibers and have a pitch of about one turn per 4 um. Sensorin immunostaining was particularly intense in varicosities, both along peripheral fibers and along the coiled structure. The localization of sensorin suggests that it may be released peripherally where it could have various paracrine and/or autocrine neuromodulatory actions.     

Functions of the LE sensory neurons inAplysia

Mechanosensory neurons which innervate the siphon and have their cell bodies in the LE cluster of the abdominal ganglion ofAplysia have revealed many cellular and molecular processes that may play general roles in learning and memory. It was initially suggested that these cells are largely responsible for triggering the gill-withdrawal reflex evoked by weak siphon stimulation, and that most of this effect is mediated by their monosynaptic connections to gill motor neurons. This implied a simple link between plasticity at these synapses and modifications of the reflex during learning. We review more recent studies from several laboratories showing that the LE cells are not activated by very weak tactile stimuli that elicit the gill-withdrawal reflex, and that an unidentified population of siphon sensory neurons has lower mechanosensory thresholds and produces shorter latency responses. Furthermore, the direct connections between LE cells and gill motor neurons make a minor contribution when the reflex is elicited in pinned siphon preparations by light stimuli that weakly activate the LE cells. Because weak mechanical stimulation of the unrestrained siphon causes little or no LE cell activation, it is unlikely that, under natural conditions, sensitization or conditioning of reflex responses elicited by light siphon touch depends upon plasticity of LE cell synapses onto either motor or interneurons. The LE cells appear to function as nociceptors because they are tuned to noxious stimuli and, like mammalian nociceptors, show peripheral sensitization following nociceptive activation. This sensitization and the profound activity-dependent potentiation of LE synapses indicate that LE cell contributions to defensive reflexes should be largest during and after intense activation of the LE cells by noxious stimulation (with the LE cell plasticity contributing to long-lasting memory of peripheral injury). The LE sensory neurons offer special opportunities for direct tests of this and other hypotheses about specific mnemonic functions of fundamental mechanisms of neural plasticity.     

Effects of the neurotrophic factor artemin on sensory afferent development and sensitivity

Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family.Its receptor GFRα3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia(DRG and TG).These neurons co-express the heat,capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1.To further investigate the effects of artemin on sensory neurons,we isolated transgenic mice(ARTN-OE mice) that overexpress art...     

Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential

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