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Journal articles on the topic 'Peripheral sensory neurons'
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Shin, Grace Ji-eun, Maria Elena Pero, Luke A. Hammond, Anita Burgos, Atul Kumar, Samantha E. Galindo, Tanguy Lucas, Francesca Bartolini, and Wesley B. Grueber. "Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy." Proceedings of the National Academy of Sciences 118, no. 15 (April 5, 2021): e2006050118. http://dx.doi.org/10.1073/pnas.2006050118.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractableDrosophilamodel and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment ofDrosophilalarvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin β-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons.
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McHugh, Jeannette M., and William B. McHugh. "Diabetes and Peripheral Sensory Neurons." AACN Clinical Issues: Advanced Practice in Acute and Critical Care 15, no. 1 (January 2004): 136–49. http://dx.doi.org/10.1097/00044067-200401000-00012.
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Marvaldi, Letizia, Nicolas Panayotis, Stefanie Alber, Shachar Y. Dagan, Nataliya Okladnikov, Indrek Koppel, Agostina Di Pizio, et al. "Importin α3 regulates chronic pain pathways in peripheral sensory neurons." Science 369, no. 6505 (August 13, 2020): 842–46. http://dx.doi.org/10.1126/science.aaz5875.
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How is neuropathic pain regulated in peripheral sensory neurons? Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control pain responsiveness in peripheral sensory neurons in mice. Importin α3 knockout or sensory neuron–specific knockdown in mice reduced responsiveness to diverse noxious stimuli and increased tolerance to neuropathic pain. Importin α3–bound c-Fos and importin α3–deficient neurons were impaired in c-Fos nuclear import. Knockdown or dominant-negative inhibition of c-Fos or c-Jun in sensory neurons reduced neuropathic pain. In silico screens identified drugs that mimic importin α3 deficiency. These drugs attenuated neuropathic pain and reduced c-Fos nuclear localization. Thus, perturbing c-Fos nuclear import by importin α3 in peripheral neurons can promote analgesia.
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Oakley, R. A., A. S. Garner, T. H. Large, and E. Frank. "Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death." Development 121, no. 5 (May 1, 1995): 1341–50. http://dx.doi.org/10.1242/dev.121.5.1341.
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To determine if muscle sensory neurons require neurotrophin-3 (NT3) during the period of normal cell death, we used an NT3-specific antiserum to deplete NT3 from peripheral tissues during this period in chick embryos. DiI staining of dorsal roots indicated that limb injections of anti-NT3 reduced the spinal projection of muscle spindle afferents. In contrast, injection of the antiserum into the spinal cord had no demonstrable effect, indicating that the reduced projection following limb injection was due to peripheral blockade of NT3 signaling. Counts of neurons retrogradely labeled from muscle and cutaneous nerves showed that peripheral blockade of NT3 selectively reduced the survival of muscle sensory neurons without affecting the survival of cutaneous sensory neurons or motoneurons. In situ hybridization with trkC probes indicated that, during the period of cell death, most large diameter muscle sensory neurons express trkC transcripts, whereas few cutaneous neurons express this receptor for NT3. We conclude that large diameter muscle afferents, including spindle afferents, require NT3 from peripheral tissues to survive the normal period of sensory neuron death in vivo.
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Tucker, Budd A., and Karen M. Mearow. "Peripheral Sensory Axon Growth: From Receptor Binding to Cellular Signaling." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 35, no. 5 (November 2008): 551–66. http://dx.doi.org/10.1017/s0317167100009331.
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Regeneration following axonal injury of the adult peripheral sensory nervous system is heavily influenced by factors located in a neuron's extracellular environment. These factors include neurotrophins, such as Nerve Growth Factor (NGF) and the extracellular matrix, such as laminin. The presence of these molecules in the peripheral nervous system (PNS) is a major contributing factor for the dichotomy between regenerative capacities of central vs. peripheral neurons. Although PNS neurons are capable of spontaneous regeneration, this response is critically dependent on many different factors including the type, location and severity of the injury. In this article, we will focus on the plasticity of adult dorsal root ganglion (DRG) sensory neurons and how trophic factors and the extracellular environment stimulate the activation of intracellular signaling cascades that promote axonal growth in adult dorsal root ganglion neurons.
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Yadav, Smita, Susan H. Younger, Linghua Zhang, Katherine L. Thompson-Peer, Tun Li, Lily Y. Jan, and Yuh Nung Jan. "Glial ensheathment of the somatodendritic compartment regulates sensory neuron structure and activity." Proceedings of the National Academy of Sciences 116, no. 11 (February 25, 2019): 5126–34. http://dx.doi.org/10.1073/pnas.1814456116.
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Sensory neurons perceive environmental cues and are important of organismal survival. Peripheral sensory neurons interact intimately with glial cells. While the function of axonal ensheathment by glia is well studied, less is known about the functional significance of glial interaction with the somatodendritic compartment of neurons. Herein, we show that three distinct glia cell types differentially wrap around the axonal and somatodendritic surface of the polymodal dendritic arborization (da) neuron of the Drosophila peripheral nervous system for detection of thermal, mechanical, and light stimuli. We find that glial cell-specific loss of the chromatin modifier gene dATRX in the subperineurial glial layer leads to selective elimination of somatodendritic glial ensheathment, thus allowing us to investigate the function of such ensheathment. We find that somatodendritic glial ensheathment regulates the morphology of the dendritic arbor, as well as the activity of the sensory neuron, in response to sensory stimuli. Additionally, glial ensheathment of the neuronal soma influences dendritic regeneration after injury.
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Hanani, Menachem. "How Is Peripheral Injury Signaled to Satellite Glial Cells in Sensory Ganglia?" Cells 11, no. 3 (February 1, 2022): 512. http://dx.doi.org/10.3390/cells11030512.
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Injury or inflammation in the peripheral branches of neurons of sensory ganglia causes changes in neuronal properties, including excessive firing, which may underlie chronic pain. The main types of glial cell in these ganglia are satellite glial cells (SGCs), which completely surround neuronal somata. SGCs undergo activation following peripheral lesions, which can enhance neuronal firing. How neuronal injury induces SGC activation has been an open question. Moreover, the mechanisms by which the injury is signaled from the periphery to the ganglia are obscure and may include electrical conduction, axonal and humoral transport, and transmission at the spinal level. We found that peripheral inflammation induced SGC activation and that the messenger between injured neurons and SGCs was nitric oxide (NO), acting by elevating cyclic guanosine monophosphate (cGMP) in SGCs. These results, together with work from other laboratories, indicate that a plausible (but not exclusive) mechanism for neuron-SGCs interactions can be formulated as follows: Firing due to peripheral injury induces NO formation in neuronal somata, which diffuses to SGCs. This stimulates cGMP synthesis in SGCs, leading to their activation and to other changes, which contribute to neuronal hyperexcitability and pain. Other mediators such as proinflammatory cytokines probably also contribute to neuron-SGC communications.
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McCallum, J. Bruce, Wai-Meng Kwok, Damir Sapunar, Andreas Fuchs, and Quinn H. Hogan. "Painful Peripheral Nerve Injury Decreases Calcium Current in Axotomized Sensory Neurons." Anesthesiology 105, no. 1 (July 1, 2006): 160–68. http://dx.doi.org/10.1097/00000542-200607000-00026.
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Background Reports of Ca(2+) current I(Ca) loss after injury to peripheral sensory neurons do not discriminate between axotomized and spared neurons. The spinal nerve ligation model separates axotomized from spared neurons innervating the same site. The authors hypothesized that I(Ca) loss is a result of neuronal injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4 neurons, as well as neurons from rats undergoing skin incision alone. Methods After behavioral testing, dissociated neurons from L4 and L5 dorsal root ganglia were studied in both current and voltage patch clamp modes. The biophysical consequence of I(Ca) loss on the action potential was confirmed using selective I(Ca) antagonists. Data were grouped into small, medium, and large cells for comparison. Results Reduced I(Ca) was predominantly a consequence of axotomy (L5 after spinal nerve ligation) and was most evident in small and medium neurons. ICa losses were associated with action potential prolongation in small and medium cells, whereas the amplitude and duration of after hyperpolarization was reduced in medium and large neurons. Blockade with Ca(2+) channel antagonists showed that action potential prolongation and after hyperpolarization diminution were alike, attributable to the loss of I(Ca). Conclusion Axotomy is required for I(Ca) loss. I(Ca) loss correlated with changes in the biophysical properties of sensory neuron membranes during action potential generation, which were due to I(Ca) loss leading to decreased outward Ca(2+)-sensitive K currents. Taken together, these results suggest that neuropathic pain may be mediated, in part, by loss of I(Ca) and the cellular processes dependent on Ca(2+).
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Tanaka, Yasumusa, Yoshikazu Yoshida, and Minoru Hirano. "CGRP-immunoreactive cells supplying laryngeal sensory nerve fibres in the cat's nodose ganglion." Journal of Laryngology & Otology 107, no. 10 (October 1993): 916–19. http://dx.doi.org/10.1017/s0022215100124788.
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AbstractThrough a combination of retrograde staining by wheat germ agglutinin (WGA) and immunohistochemistry, calcitonin gene-related peptide (CGRP)-reactive sensory neurons projecting from the laryngeal mucosa were detected in the feline nodose ganglion. The size of the CGRP-immunoreactive cell which was regarded as a laryngeal sensory neuron, was about 60 ±m in diameter: the shape of the immunoreactive laryngeal sensory neuron was unipolar. CGRP-reacted laryngeal sensory cells were found in the rostral part of the nodose ganglion extending to the middle part. They aggregated in the most rostral part, were sparse in other parts and were approximately 50 per cent of WGA-reactive laryngeal sensory neurons in number. Our results suggest that this neurotransmitter might play an important role in laryngeal peripheral sensory innervation.
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Gheorghe, Roxana-Olimpia, Andreea Violeta Grosu, Melania Bica-Popi, and Violeta Ristoiu. "The Yin/Yang Balance of Communication between Sensory Neurons and Macrophages in Traumatic Peripheral Neuropathic Pain." International Journal of Molecular Sciences 23, no. 20 (October 16, 2022): 12389. http://dx.doi.org/10.3390/ijms232012389.
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Traumatic peripheral neuropathic pain is a complex syndrome caused by a primary lesion or dysfunction of the peripheral nervous system. Secondary to the lesion, resident or infiltrating macrophages proliferate and initiate a cross-talk with the sensory neurons, at the level of peripheral nerves and sensory ganglia. The neuron–macrophage interaction, which starts very early after the lesion, is very important for promoting pain development and for initiating changes that will facilitate the chronicization of pain, but it also has the potential to facilitate the resolution of injury-induced changes and, consequently, promote the reduction of pain. This review is an overview of the unique characteristics of nerve-associated macrophages in the peripheral nerves and sensory ganglia and of the molecules and signaling pathways involved in the neuro-immune cross-talk after a traumatic lesion, with the final aim of better understanding how the balance between pro- and anti-nociceptive dialogue between neurons and macrophages may be modulated for new therapeutic approaches.
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West, Christian Alexander, Andrew McKay Hart, Giorgio Terenghi, and Mikael Wiberg. "Sensory Neurons of the Human Brachial Plexus." Neurosurgery 70, no. 5 (October 27, 2011): 1183–94. http://dx.doi.org/10.1227/neu.0b013e318241ace1.
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Abstract BACKGROUND: Extensive neuron death following peripheral nerve trauma is implicated in poor sensory recovery. Translational research for experimentally proven neuroprotective drugs requires knowledge of the numbers and distribution of sensory neurons in the human upper limb and a novel noninvasive clinical measure of neuron loss. OBJECTIVE: To compare optical fractionation and volumetric magnetic resonance imaging (MRI) of dorsal root ganglia (DRG) in histological quantification and objective clinical assessment of human brachial plexus sensory neurons. METHODS: Bilateral C5-T1 DRG were harvested from 5 human cadavers for stereological volume measurement and sensory neuron counts (optical fractionator). MRI scans were obtained from 14 healthy volunteers for volumetric analysis of C5-T1 DRG. RESULTS: The brachial plexus is innervated by 425 409 (standard deviation 15 596) sensory neurons with a significant difference in neuron counts and DRG volume between segmental levels (P < .001), with C7 ganglion containing the most. DRG volume correlated with neuron counts (r = 0.75, P < .001). Vertebral artery pulsation hindered C5 and 6 imaging, yet high-resolution MRI of C7, C8, and T1 DRG permitted unbiased volume measurement. In accord with histological analysis, MRI confirmed a significant difference between C7, C8, and T1 DRG volume (P < .001), interindividual variability (CV = 15.3%), and sex differences (P = .04). Slight right-left sided disparity in neuron counts (2.5%, P = .04) was possibly related to hand dominance, but no significant volume disparity existed. CONCLUSION: Neuron counts for the human brachial plexus are presented. These correlate with histological DRG volumes and concur with volumetric MRI results in human volunteers. Volumetric MRI of C7-T1 DRG is a legitimate noninvasive proxy measure of sensory neurons for clinical study.
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Bévengut, Michelle, François Clarac, and Daniel Cattaert. "Antidromic Modulation of a Proprioceptor Sensory Discharge in Crayfish." Journal of Neurophysiology 78, no. 2 (August 1, 1997): 1180–83. http://dx.doi.org/10.1152/jn.1997.78.2.1180.
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Bévengut, Michelle, François Clarac, and Daniel Cattaert. Antidromic modulation of a proprioceptor sensory discharge in crayfish. J. Neurophysiol. 78: 1180–1183, 1997. In the proprioceptive neurons of the coxo-basal chortotonal organ, orthodromic spikes convey the sensory information from the cell somata (located peripherally) to the central output terminals. During fictive locomotion, presynaptic depolarizations of these central terminals elicit bursts of antidromic spikes that travel back to the periphery. To determine whether the antidromic spikes modified the orthodromic activity of the sensory neurons, single identified primary afferents of the proprioceptor were recorded intracellularly and stimulated in in vitro preparations of crayfish nervous system. Depolarizing current pulses were delivered in trains whose frequency and duration were controlled to reproduce bursts of antidromic spikes similar to those elicited during fictive locomotion. According to their frequencies, these antidromic bursts reduce or suppress the orthodromic discharges in both position- and movement-sensitive neurons. They induce both a long-lasting silence and a gradual recovery after their occurrences. Neither the collision between the afferent and the efferent messages nor the release of serotonin by the sensory neurons can explain these results. We therefore conclude that antidromic bursts produce a peripheral modulation of the orthodromic activity of the sensory neurons, modifying their sensitivity by mechanisms yet unknown.
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Dulin, M. F., I. Steffensen, C. E. Morris, and E. T. Walters. "Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica." Journal of Experimental Biology 198, no. 10 (October 1, 1995): 2055–66. http://dx.doi.org/10.1242/jeb.198.10.2055.
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Recovery of behavioural and sensory function was examined following unilateral pedal nerve crush in Aplysia californica. Nerve crush that transected all axons connecting the tail to the central nervous system (CNS) eliminated the ipsilateral tail-evoked siphon reflex, whose sensory input travels in the crushed tail nerve (p9). The first reliable signs of recovery of this reflex were observed within 1 week, and most animals displayed tail-evoked siphon responses within 2 weeks. Wide-dynamic-range mechanosensory neurons with somata in the ventrocaudal (VC) cluster of the ipsilateral pleural ganglion exhibited a few receptive fields (RFs) on the tail 3 weeks after unilateral pedal nerve crush, indicating that the RFs had either regenerated or been reconnected to the central somata. These RFs were smaller and sensitized compared with corresponding RFs on the contralateral, uncrushed side. Centrally conducted axon responses of VC sensory neurones to electrical stimulation distal to the nerve crush site did not reappear until at least 10 days after the crush. Because the crush site was much closer to the CNS than to the tail, the failure of axon responses to be restored earlier than the behavioural responses indicates that early stages of reflex recovery are not due to regeneration of VC sensory neurone axons into the tail. Following nerve crush, VC sensory neurones often could be activated by stimulating central connectives or peripheral nerves that do not normally contain the sensory neurone's axons. These results suggest that recovery of behavioral function after nerve injury involves complex mechanisms, including regenerative growth of axotomized VC sensory neurones, sensitization of regenerating RFs and sprouting of VC sensory neurone fibres within the CNS. Furthermore, the rapidity of behavioural recovery indicates that its initial phases are mediated by additional mechanisms, perhaps centripetal regeneration of unidentified sensory neurones having peripheral somata, or transient reconnection of proximal and distal stumps of axotomized VC cells.
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Meier, T., F. Chabaud, and H. Reichert. "Homologous patterns in the embryonic development of the peripheral nervous system in the grasshopper Schistocerca gregaria and the fly Drosophila melanogaster." Development 112, no. 1 (May 1, 1991): 241–53. http://dx.doi.org/10.1242/dev.112.1.241.
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To determine the generality of developmental mechanisms involved in the construction of the insect nervous system, the embryonic development of the peripheral nervous system in the grasshopper Schistocerca gregaria was characterized at the level of identified neurons and nerve branches and then compared to that previously described from the fly Drosophila melanogaster. For this, immunocytochemistry using a neuron-specific antibody was carried out on staged grasshopper embryos. Our results show that initially a simple peripheral nerve scaffolding is established in each segment of the animal. This scaffolding consists of a pair of intersegmental nerves that are formed by identified afferent and efferent pioneer neurons and a pair of segmental nerves that are formed by afferent pioneers situated in limb buds. Subsequently, identified sets of sensory neurons differentiate in a stereotyped spatiotemporal pattern in dorsal, lateral and ventral clusters in each segment and project their axons onto these nerves. Although segment-specific differences exist, serial homologs of the developing nerves and sensory neurons can be identified. A comparison of these results with those obtained from Drosophila shows that virtually the same pattern of peripheral nerves and sensory structures is formed in both species. This indicates that the construction of the peripheral nervous system in extremely divergent modern insects relies on conserved developmental mechanisms that evolved in ancestral insects over 300 million years ago.
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O-Sullivan, InSug, Ranjan Kc, Gurjit Singh, Vaskar Das, Kaige Ma, Xin Li, Fackson Mwale, et al. "Sensory Neuron-Specific Deletion of Tropomyosin Receptor Kinase A (TrkA) in Mice Abolishes Osteoarthritis (OA) Pain via NGF/TrkA Intervention of Peripheral Sensitization." International Journal of Molecular Sciences 23, no. 20 (October 11, 2022): 12076. http://dx.doi.org/10.3390/ijms232012076.
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Tropomyosin receptor kinase A (TrkA/NTRK1) is a high-affinity receptor for nerve growth factor (NGF), a potent pain mediator. NGF/TrkA signaling elevates synovial sensory neuronal distributions in the joints and causes osteoarthritis (OA) pain. We investigated the mechanisms of pain transmission as to whether peripheral sensory neurons are linked to the cellular plasticity in the dorsal root ganglia (DRG) and are critical for OA hyperalgesia. Sensory neuron-specific deletion of TrkA was achieved by tamoxifen injection in 4-week-old TrkAfl/fl;NaV1.8CreERT2 (Ntrk1 fl/fl;Scn10aCreERT2) mice. OA was induced by partial medial meniscectomy (PMM) in 12-week-old mice, and OA-pain-related behavior was analyzed for 12 weeks followed by comprehensive histopathological examinations. OA-associated joint pain was markedly improved without cartilage protection in sensory-neuron-specific conditional TrkA knock-out (cKO) mice. Alleviated hyperalgesia was associated with suppression of the NGF/TrkA pathway and reduced angiogenesis in fibroblast-like synovial cells. Elevated pain transmitters in the DRG of OA-induced mice were significantly diminished in sensory-neuron-specific TrkA cKO and global TrkA cKO mice. Spinal glial activity and brain-derived neurotropic factor (BDNF) were significantly increased in OA-induced mice but were substantially eliminated by sensory-neuron-specific deletion. Our results suggest that augmentation of NGF/TrkA signaling in the joint synovium and the peripheral sensory neurons facilitate pro-nociception and centralized pain sensitization.
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Chada, S., P. Lamoureux, R. E. Buxbaum, and S. R. Heidemann. "Cytomechanics of neurite outgrowth from chick brain neurons." Journal of Cell Science 110, no. 10 (May 15, 1997): 1179–86. http://dx.doi.org/10.1242/jcs.110.10.1179.
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Mechanical tension is a direct and immediate stimulus for neurite initiation and elongation from peripheral neurons. We report here that the relationship between tension and neurite outgrowth is equally initimate for embryonic chick forebrain neurons. Culture of forebrain neurons was unusually simple and reliable, and some of these cells undergo early events of axonal-dendritic polarity. Neurite outgrowth can be initiated de novo by experimental application of tension to the cell margin of forebrain neurons placed into culture 8–12 hours earlier, prior to spontaneous neurite outgrowth. Experimentally induced neurite elongation from these neurons shows the same robust linear relationship between elongation rate and magnitude of applied tension as peripheral neurons, i.e. both show a fluid-like growth response to tension. Although forebrain and sensory neurons manifest a similar distribution of growth sensitivity to tension (growth rate/unit tension), chick forebrain neurons initiated and elongated neurites at substantially lower net tensions than peripheral neurons. This is because, unlike peripheral neurons, there is no minimum threshold tension required for elongation in forebrain neurons; all positive tensions stimulate neurite outgrowth. Consistent with this observation, chick forebrain neurons showed weak retractile behavior in response to slackening compared to sensory neurons. Neurites that were slackened showed only transient elastic behavior and never actively produced tension, as do chick sensory neurons after slackening. We conclude that tension is an important regulator of both peripheral and central neuronal growth, but that elastic behavior is much weaker for forebrain neurons than peripheral neurons from the same developing organism. These data have significance for the understanding of the morphogenetic events of brain development.
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Blanchard, Joel W., Kevin T. Eade, Attila Szűcs, Valentina Lo Sardo, Rachel K. Tsunemoto, Daniel Williams, Pietro Paolo Sanna, and Kristin K. Baldwin. "Selective conversion of fibroblasts into peripheral sensory neurons." Nature Neuroscience 18, no. 1 (November 24, 2014): 25–35. http://dx.doi.org/10.1038/nn.3887.
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Avenali, Luca, Oli Abate Fulas, Julia Sondermann, Pratibha Narayanan, David Gomez-Varela, and Manuela Schmidt. "Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons." Channels 11, no. 1 (July 14, 2016): 11–19. http://dx.doi.org/10.1080/19336950.2016.1207025.
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Ghysen, Alain, Christine Dambly-Chaudi�re, Efrain Aceves, Lily Yeh Jan, and Yuh Nung Jan. "Sensory neurons and peripheral pathways in Drosophila embryos." Roux's Archives of Developmental Biology 195, no. 5 (July 1986): 281–89. http://dx.doi.org/10.1007/bf00376060.
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King, Chih H., Eric Lancaster, Daniela Salomon, Elior Peles, and Steven S. Scherer. "Kv7.2 regulates the function of peripheral sensory neurons." Journal of Comparative Neurology 522, no. 14 (April 12, 2014): 3262–80. http://dx.doi.org/10.1002/cne.23595.
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Wu, Zizhen, Gabor Toro, Guoying Xu, Danny Dang, Charmaine Prater, and Qing Yang. "Paclitaxel Inhibits KCNQ Channels in Primary Sensory Neurons to Initiate the Development of Painful Peripheral Neuropathy." Cells 11, no. 24 (December 15, 2022): 4067. http://dx.doi.org/10.3390/cells11244067.
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Cancer patients undergoing paclitaxel infusion usually experience peripheral nerve degeneration and serious neuropathic pain termed paclitaxel-induced peripheral neuropathy (PIPN). However, alterations in the dose or treatment schedule for paclitaxel do not eliminate PIPN, and no therapies are available for PIPN, despite numerous studies to uncover the mechanisms underlying the development/maintenance of this condition. Therefore, we aimed to uncover a novel mechanism underlying the pathogenesis of PIPN. Clinical studies suggest that acute over excitation of primary sensory neurons is linked to the pathogenesis of PIPN. We found that paclitaxel-induced acute hyperexcitability of primary sensory neurons results from the paclitaxel-induced inhibition of KCNQ potassium channels (mainly KCNQ2), found abundantly in sensory neurons and axons. We found that repeated application of XE-991, a specific KCNQ channel blocker, induced PIPN-like alterations in rats, including mechanical hypersensitivity and degeneration of peripheral nerves, as detected by both morphological and behavioral assays. In contrast, genetic deletion of KCNQ2 from peripheral sensory neurons in mice significantly attenuated the development of paclitaxel-induced peripheral sensory fiber degeneration and chronic pain. These findings may lead to a better understanding of the causes of PIPN and provide an impetus for developing new classes of KCNQ activators for its therapeutic treatment.
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Grigg, Peter. "Peripheral Neural Mechanisms in Proprioception." Journal of Sport Rehabilitation 3, no. 1 (February 1994): 2–17. http://dx.doi.org/10.1123/jsr.3.1.2.
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Proprioception is the sense of position and movement of the limbs. The sense arises through activity in sensory neurons located in skin, muscles, and joint tissues. Proprioception appears to be a compound sense, relying on simultaneous activity in a number of types of afferent neurons. Position sense is largely mediated by activity in muscle afferent neurons. Afferent neurons originating in soft tissues of the joints contribute a sense of joint position only when the joint is rotated into a limit of its range of motion. Joint neurons have an important role in protecting the integrity of joints if they are unstable. Afferent neurons in skin appear to contribute little to position sense but may contribute to the sense of movement.
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Alles, Sascha R. A., Filipe Nascimento, Rafael Luján, Ana P. Luiz, Queensta Millet, M. Ali Bangash, Sonia Santana-Varela, et al. "Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability." Science Advances 6, no. 8 (February 2020): eaax4568. http://dx.doi.org/10.1126/sciadv.aax4568.
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Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.
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Cox, James J., C. Geoffrey Woods, and Ingo Kurth. "Peripheral sensory neuropathies – pain loss vs. pain gain." Medizinische Genetik 32, no. 3 (September 1, 2020): 233–41. http://dx.doi.org/10.1515/medgen-2020-2039.
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Abstract Peripheral sensory neurons are afferent neurons that innervate the skin, joints, bones, muscles, and mucosal tissues. By converting different stimuli into action potentials, they transmit signals for the sensing of temperature, touch, pressure, or pain. This review discusses the known Mendelian disorders which affect pain sensing in humans. For painlessness, these disorders can be classified as developmental, neurodegenerative, or functional, where pain-sensing neurons (nociceptors) are present but cannot be activated or produce action potentials. Affected patients suffer from numbness with recurrent injuries, burns, and poorly healing wounds. For Mendelian disorders of excess pain, aberrant overactivity of nociceptors is a hallmark and leads to paroxysmal or continuous pain states. Again, the effect can be functional or, as in small fiber neuropathies, can be accompanied by degeneration of small unmyelinated nerve fibers in the skin. About 20 different genes are known to cause Mendelian pain disorders and the molecules involved are of general interest for human pain research and as analgesic targets. Comprehensive genetic testing is the key to early diagnosis and adaptation of clinical management.
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Black, Bryan J., Rahul Atmaramani, Rajeshwari Kumaraju, Sarah Plagens, Mario Romero-Ortega, Gregory Dussor, Theodore J. Price, Zachary T. Campbell, and Joseph J. Pancrazio. "Adult mouse sensory neurons on microelectrode arrays exhibit increased spontaneous and stimulus-evoked activity in the presence of interleukin-6." Journal of Neurophysiology 120, no. 3 (September 1, 2018): 1374–85. http://dx.doi.org/10.1152/jn.00158.2018.
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Following inflammation or injury, sensory neurons located in the dorsal root ganglia (DRG) may exhibit increased spontaneous and/or stimulus-evoked activity, contributing to chronic pain. Current treatment options for peripherally mediated chronic pain are highly limited, driving the development of cell- or tissue-based phenotypic (function-based) screening assays for peripheral analgesic and mechanistic lead discovery. Extant assays are often limited by throughput, content, use of tumorigenic cell lines, or tissue sources from immature developmental stages (i.e., embryonic or postnatal). Here, we describe a protocol for culturing adult mouse DRG neurons on substrate-integrated multiwell microelectrode arrays (MEAs). This approach enables multiplexed measurements of spontaneous as well as stimulus-evoked extracellular action potentials from large populations of cells. The DRG cultures exhibit stable spontaneous activity from 9 to 21 days in vitro. Activity is readily evoked by known chemical and physical agonists of sensory neuron activity such as capsaicin, bradykinin, PGE2, heat, and electrical field stimulation. Most importantly, we demonstrate that both spontaneous and stimulus-evoked activity may be potentiated by incubation with the inflammatory cytokine interleukin-6 (IL-6). Acute responsiveness to IL-6 is inhibited by treatment with a MAPK-interacting kinase 1/2 inhibitor, cercosporamide. In total, these findings suggest that adult mouse DRG neurons on multiwell MEAs are applicable to ongoing efforts to discover peripheral analgesic and their mechanisms of action. NEW & NOTEWORTHY This work describes methodologies for culturing spontaneously active adult mouse dorsal root ganglia (DRG) sensory neurons on microelectrode arrays. We characterize spontaneous and stimulus-evoked adult DRG activity over durations consistent with pharmacological interventions. Furthermore, persistent hyperexcitability could be induced by incubation with inflammatory cytokine IL-6 and attenuated with cercosporamide, an inhibitor of the IL-6 sensitization pathway. This constitutes a more physiologically relevant, moderate-throughput in vitro model for peripheral analgesic screening as well as mechanistic lead discovery.
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Malacrida, Alessio, Cristina Meregalli, Virginia Rodriguez-Menendez, and Gabriella Nicolini. "Chemotherapy-Induced Peripheral Neuropathy and Changes in Cytoskeleton." International Journal of Molecular Sciences 20, no. 9 (May 9, 2019): 2287. http://dx.doi.org/10.3390/ijms20092287.
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Despite the different antineoplastic mechanisms of action, peripheral neurotoxicity induced by all chemotherapy drugs (anti-tubulin agents, platinum compounds, proteasome inhibitors, thalidomide) is associated with neuron morphological changes ascribable to cytoskeleton modifications. The “dying back” degeneration of distal terminals (sensory nerves) of dorsal root ganglia sensory neurons, observed in animal models, in in vitro cultures and biopsies of patients is the most evident hallmark of the perturbation of the cytoskeleton. On the other hand, in highly polarized cells like neurons, the cytoskeleton carries out its role not only in axons but also has a fundamental role in dendrite plasticity and in the organization of soma. In the literature, there are many studies focused on the antineoplastic-induced alteration of microtubule organization (and consequently, fast axonal transport defects) while very few studies have investigated the effect of the different classes of drugs on microfilaments, intermediate filaments and associated proteins. Therefore, in this review, we will focus on: (1) Highlighting the fundamental role of the crosstalk among the three filamentous subsystems and (2) investigating pivotal cytoskeleton-associated proteins.
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Panek, Izabela, Shannon Meisner, and Päivi H. Torkkeli. "Distribution and Function of GABAB Receptors in Spider Peripheral Mechanosensilla." Journal of Neurophysiology 90, no. 4 (October 2003): 2571–80. http://dx.doi.org/10.1152/jn.00321.2003.
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The mechanosensilla in spider exoskeleton are innervated by bipolar neurons with their cell bodies close to the cuticle and dendrites attached to it. Numerous efferent fibers synapse with peripheral parts of the mechanosensory neurons, with glial cells surrounding the neurons, and with each other. Most of these efferent fibers are immunoreactive to γ-aminobutyric acid (GABA), and the sensory neurons respond to agonists of ionotropic GABA receptors with a rapid and complete inhibition. In contrast, little is known about metabotropic GABAB receptors that may mediate long-term effects. We investigated the distribution of GABAB receptors on spider leg mechanosensilla using specific antibodies against 2 proteins needed to form functional receptors and an antibody that labels the synaptic vesicles on presynaptic sites. Both anti-GABAB receptor antibodies labeled the distal parts of the sensory cell bodies and dendrites but anti-GABABR1 immunoreactivity was also found in the axons and proximal parts of the cell bodies and some glial cells. The fine efferent fibers that branch on top of the sensory neurons did not show GABAB receptor immunoreactivity but were densely labeled with anti-synapsin and indicated synaptic vesicles on presynaptic locations to the GABAB receptors. Intracellular recordings from sensory neurons innervating the slit sensilla of the spider legs revealed that application of GABAB receptor agonists attenuated voltage-activated Ca2+ current and enhanced voltage-activated outward K+ current, providing 2 possible mechanisms for controlling the neurons' excitability. These findings support the hypothesis that GABAB receptors are present in the spider mechanosensilla where their activation may modulate information transmission.
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Pecze, László, Péter Pelsőczi, Miklós Kecskés, Zoltán Winter, András Papp, Krisztián Kaszás, Tamás Letoha, Csaba Vizler, and Zoltán Oláh. "Resiniferatoxin Mediated Ablation of TRPV1+ Neurons Removes TRPA1 as Well." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 36, no. 2 (March 2009): 234–41. http://dx.doi.org/10.1017/s0317167100006600.
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Objectives:Resiniferatoxin, the most potent agonist of inflammatory pain/vanilloid receptor/cation channel (TRPV1) can be used for neuron subtype specific ablation of pain generating cells at the level of the peripheral nervous system by Ca2+-excytotoxicity. Molecular neurosurgery is an emerging technology either to alleviate severe pain in cancer or treat/prevent different local neuropathies. Our aim was determining sensory modalities that may be lost after resiniferatoxin treatment.Methods:Newborn or adult mice were treated with resiniferatoxin, then changes in chemical and heat sensitivity were correlated with alterations of the cell composition of sensory ganglions.Results:Only mice treated at adult age became less sensitive to heat stimuli, while both treatment groups lost sensitivity to specific vanilloid agonists of TRPV1 and, interestingly, to allyl-isothiocyanate, a selective agonist of TRPA1. Our in vivo and post mortem analytical results confirmed that TRPV1 and TRPA1 function together and resiniferatoxin-mediated neurosurgery removes both sensor moleculesDiscussion:In adult mice resiniferatoxin causes: i) desensitization to heat and ii) sensitization to cold. Cold hyperalgesia, an imbalance in thermosensation, might be conferred by a prominent cold receptor that is expressed in surviving resiniferatoxin-resistant sensory neurons and compensates for pain signals lost with TRPA1 and TRPV1 double positive cells in the peripheral nervous system.
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Nie, Hui, Haijun Zhang, and Han-Rong Weng. "Bidirectional Neuron–Glia Interactions Triggered by Deficiency of Glutamate Uptake at Spinal Sensory Synapses." Journal of Neurophysiology 104, no. 2 (August 2010): 713–25. http://dx.doi.org/10.1152/jn.00282.2010.
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Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-d-aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron–glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons—they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways.
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Stemkowski, Patrick L., and Peter A. Smith. "Long-term IL-1β exposure causes subpopulation-dependent alterations in rat dorsal root ganglion neuron excitability." Journal of Neurophysiology 107, no. 6 (March 15, 2012): 1586–97. http://dx.doi.org/10.1152/jn.00587.2011.
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The effect of interleukin-1β (IL-1β) on the electrical properties of sensory neurons was assessed at levels and exposure times comparable to those found in animal models of neuropathic pain. Experiments involved whole cell current-clamp recordings from rat dorsal root ganglion (DRG) neurons in defined-medium, neuron-enriched cultures. Five- to six-day exposure to 100 pM IL-1β produced subpopulation-dependent effects on DRG neurons. These included an increase in the excitability of medium-diameter and small-diameter isolectin B4 (IB4)-positive neurons that was comparable to that found after peripheral nerve injury. By contrast, a reduction in excitability was observed in large-diameter neurons, while no effect was found in small-diameter IB4-negative neurons. Further characterization of changes in medium and small IB4-positive neurons revealed that some, but not all, effects of IL-1β were mediated through its receptor, IL-1RI. Although the acute actions of IL-1β on sensory neurons have been well studied and related to acute and/or inflammatory pain, the present study shows how sensory neurons respond to long-term cytokine exposure. Such effects are relevant to understanding processes that contribute to the onset of neuropathic pain.
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Clatworthy, A. L., and E. T. Walters. "Activity-dependent depression of mechanosensory discharge in Aplysia." Journal of Neurophysiology 70, no. 3 (September 1, 1993): 1195–209. http://dx.doi.org/10.1152/jn.1993.70.3.1195.
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1. Inhibition of action potential discharge in Aplysia mechanosensory neurons after noxious stimulation has not been described previously. The present studies investigated depressive effects of prolonged noxious stimulation and repetitive intracellular activation on the number and latency of action potentials evoked by test stimuli applied to the tail or the nerve innervating the tail. Action potential discharge was monitored in the somata of mechanonociceptors in the pleural ganglia. 2. Repeated brief pinches delivered at 5-s intervals to a sensory neuron's receptive field on the tail initially caused intense activation (10-25 spikes recorded in the soma) followed by a progressive decrease or "wind-down" of spike number during subsequent pinches. 3. Repeated application to the tail of noxious shock that caused intense activation of sensory neurons (10-22 spikes during the initial shock) produced progressive wind-down of discharge similar to that produced by repeated tail pinch. However, sensory neurons that showed lower activation (1-9 spikes) to the same shock displayed wind-up of discharge during the 10 shocks. These results suggested that prolonged, intense activation depresses subsequent action potential discharge. 4. Changes in the time required for spikes evoked in the tail to reach the central soma were used as an indicator of changes in the excitability and/or conduction velocity of peripheral branches. Repeated pinch within a sensory neuron's receptive field caused an increase in the latency of discharge elicited by test shocks within the receptive field that lasted > or = 10 min. Repetitive intracellular stimulation of the sensory neuron soma caused a similar increase in latency. 5. Repetitive soma activation decreased the number of spikes evoked 10 s later by a test shock in the sensory neuron's receptive field, indicating that spike activity depresses the initiation and/or conduction of spikes in peripheral branches. Surprisingly, repeated pinch to the receptive field caused no significant change in the number of spikes evoked by the same test shock. This difference suggests that tail pinch produces concomitant facilitatory effects that oppose the depressive effects of intense spike activity. 6. Depressive effects of repeated pinch and repetitive soma activation were expressed in the axon between the receptive field and the CNS. Spikes evoked by brief test shocks delivered to the nerve containing the axon of the recorded sensory neuron showed a transient increase in latency (perhaps due to a decrease in conduction velocity) after either procedure. Repeated pinch, but not repetitive soma activation, also caused an increase in spike threshold in the nerve.(ABSTRACT TRUNCATED AT 400 WORDS)
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Browning, Kirsteen N., and David Mendelowitz. "II. Integration of afferent signaling from the viscera by the nodose ganglia." American Journal of Physiology-Gastrointestinal and Liver Physiology 284, no. 1 (January 1, 2003): G8—G14. http://dx.doi.org/10.1152/ajpgi.00322.2002.
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To understand vago-vagal reflexes, one must have an appreciation of the events surrounding the encoding, integration, and central transfer of peripheral sensations by vagal afferent neurons. A large body of work has shown that vagal afferent neurons have nonuniform properties and that distinct subpopulations of neurons exist within the nodose ganglia. These sensory neurons display a considerable degree of plasticity; electrophysiological, pharmacological, and neurochemical properties have all been shown to alter after peripheral tissue injury. The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neuronal neighbors. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target.
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YU, HSIN-HAO, and MARCELLO G. P. ROSA. "Uniformity and diversity of response properties of neurons in the primary visual cortex: Selectivity for orientation, direction of motion, and stimulus size from center to far periphery." Visual Neuroscience 31, no. 1 (October 25, 2013): 85–98. http://dx.doi.org/10.1017/s0952523813000448.
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AbstractAlthough the primary visual cortex (V1) is one of the most extensively studied areas of the primate brain, very little is known about how the far periphery of visual space is represented in this area. We characterized the physiological response properties of V1 neurons in anaesthetized marmoset monkeys, using high-contrast drifting gratings. Comparisons were made between cells with receptive fields located in three regions of V1, defined by eccentricity: central (3–5°), near peripheral (5–15°), and far peripheral (>50°). We found that orientation selectivity of individual cells was similar from the center to the far periphery. Nonetheless, the proportion of orientation-selective neurons was higher in central visual field representation than in the peripheral representations. In addition, there were similar proportions of cells representing all orientations, with the exception of the representation of the far periphery, where we detected a bias favoring near-horizontal orientations. The proportions of direction-selective cells were similar throughout V1. When the center/surround organization of the receptive fields was tested with gratings with varying diameters, we found that the population of neurons that was suppressed by large gratings was smaller in the far periphery, although the strength of suppression in these cells tended to be stronger. In addition, the ratio between the diameters of the excitatory centers and suppressive surrounds was similar across the entire visual field. These results suggest that, superimposed on the broad uniformity of V1, there are subtle physiological differences, which indicate that spatial information is processed differently in the central versus far peripheral visual fields.
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Sullivan, Laura C., Teresa S. Chavera, Raehannah J. Jamshidi, Kelly A. Berg, and William P. Clarke. "Constitutive Desensitization of Opioid Receptors in Peripheral Sensory Neurons." Journal of Pharmacology and Experimental Therapeutics 359, no. 3 (September 22, 2016): 411–19. http://dx.doi.org/10.1124/jpet.116.232835.
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Kress, M., and C. Distler. "Differences in calcium signalling in rat peripheral sensory neurons." Neuroscience Letters 354, no. 2 (January 2004): 127–30. http://dx.doi.org/10.1016/j.neulet.2003.10.003.
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Wong, Willy. "On the rate coding response of peripheral sensory neurons." Biological Cybernetics 114, no. 6 (December 2020): 609–19. http://dx.doi.org/10.1007/s00422-020-00848-4.
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Åkesson, Elisabet, Martin Sandelin, Nadezda Kanaykina, Hákan Aldskogius, and Elena N. Kozlova. "Long-Term Survival, Robust Neuronal Differentiation, and Extensive Migration of Human Forebrain Stem/Progenitor Cells Transplanted to the Adult Rat Dorsal Root Ganglion Cavity." Cell Transplantation 17, no. 10-11 (October 2008): 1115–23. http://dx.doi.org/10.3727/096368908787236585.
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Neurons in dorsal root ganglia (DRGs) transmit sensory information from peripheral tissues to the spinal cord. This pathway can be interrupted, for example, as the result of physical violence, traffic accidents, or complications during child delivery. As a consequence, the patient permanently loses sensation and often develops intractable neuropathic pain in the denervated area. Here we investigate whether human neural stem/progenitor cells (hNSPCs) transplanted to the DRG cavity can serve as a source for repairing lost peripheral sensory connections. We found that hNSPCs robustly differentiate to neurons, which survive long-term transplantation. The neuronal population in the transplants was tightly surrounded by astrocytes, suggesting their active role in neuron survival. Furthermore, 3 months after grafting hNSPCs were found in the dorsal root transitional zone (DRTZ) and within the spinal cord. The level of differentiation of transplanted cells was high in the core of the transplants whereas cells that migrated to the DRTZ and spinal cord were undifferentiated, nestin-expressing precursors. These data indicate that peripherally transplanted hNPSCs can be used for repair of dorsal root avulsion or spinal cord injuries; however, additional factors are required to guide their differentiation to the desired type of neurons. Furthermore, hNPSCs that migrate from the DRG cavity graft site to the DRTZ and spinal cord may provide trophic support for regenerating dorsal root axons, thereby allowing them to reenter the host spinal cord.
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Strassman, A. M., and S. A. Raymond. "Electrophysiological Evidence for Tetrodotoxin-Resistant Sodium Channels in Slowly Conducting Dural Sensory Fibers." Journal of Neurophysiology 81, no. 2 (February 1, 1999): 413–24. http://dx.doi.org/10.1152/jn.1999.81.2.413.
Full textAbstract:
Electrophysiological evidence for tetrodotoxin-resistant sodium channels in mechanosensitive nerve endings of slowly conducting fibers in the intracranial dura. A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 μM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-δ units [conduction velocity (c.v.) 5–18 m/s] but only 50% (5/10) of slow A-δ units (1.5 <c.v.<5 m/s) and 13% (2/15) of C units (c.v. ≤1.5 m/s). The mean TTX concentration that produced complete suppression of mechanoresponsiveness was ∼270-fold higher in C units than in fast A-δ units. In contrast, no significant difference was found between C and A-δ units in the concentration of lidocaine required for complete suppression of mechanoresponsiveness, indicating that the greater TTX resistance of mechanoresponsiveness in C units is not attributable to differences in safety factor unrelated to channel subtype. These data offer indirect evidence that a TTX-resistant channel subtype is expressed in the terminal axonal branches of many of the more slowly conducting (C and slow A-δ) dural afferents. The channel appears to be present in these fibers, but not in the faster A-δ fibers, in sufficient numbers to support the initiation and propagation of mechanically induced impulses. Comparison with previous data on the absence of TTX resistance in peripheral nerve fibers suggests that the TTX-resistant sodium channel may be a distinctive feature of the receptive rather than the conductive portion of the sensory neuron’s axonal membrane.
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Shin, Seung Min, Yongsong Cai, Brandon Itson-Zoske, Chensheng Qiu, Xu Hao, Hongfei Xiang, Quinn H. Hogan, and Hongwei Yu. "Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis." Molecular Pain 16 (January 2020): 174480692096380. http://dx.doi.org/10.1177/1744806920963807.
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The monosodium iodoacetate knee osteoarthritis model has been widely used for the evaluation of osteoarthritis pain, but the pathogenesis of associated chronic pain is not fully understood. The T-type calcium channel 3.2 (CaV3.2) is abundantly expressed in the primary sensory neurons, in which it regulates neuronal excitability at both the somata and peripheral terminals and facilitates spontaneous neurotransmitter release at the spinal terminals. In this study, we investigated the involvement of primary sensory neuron-CaV3.2 activation in monosodium iodoacetate osteoarthritis pain. Knee joint osteoarthritis pain was induced by intra-articular injection of monosodium iodoacetate (2 mg) in rats, and sensory behavior was evaluated for 35 days. At that time, knee joint structural histology, primary sensory neuron injury, and inflammatory gliosis in lumbar dorsal root ganglia, and spinal dorsal horn were examined. Primary sensory neuron-T-type calcium channel current by patch-clamp recording and CaV3.2 expression by immunohistochemistry and immunoblots were determined. In a subset of animals, pain relief by CaV3.2 inhibition after delivery of CaV3.2 inhibitor TTA-P2 into sciatic nerve was investigated. Knee injection of monosodium iodoacetate resulted in osteoarthritis histopathology, weight-bearing asymmetry, sensory hypersensitivity of the ipsilateral hindpaw, and inflammatory gliosis in the ipsilateral dorsal root ganglia, sciatic nerve, and spinal dorsal horn. Neuronal injury marker ATF-3 was extensively upregulated in primary sensory neurons, suggesting that neuronal damage was beyond merely knee-innervating primary sensory neurons. T-type current in dissociated primary sensory neurons from lumbar dorsal root ganglia of monosodium iodoacetate rats was significantly increased, and CaV3.2 protein levels in the dorsal root ganglia and spinal dorsal horn ipsilateral to monosodium iodoacetate by immunoblots were significantly increased, compared to controls. Perineural application of TTA-P2 into the ipsilateral sciatic nerve alleviated mechanical hypersensitivity and weight-bearing asymmetry in monosodium iodoacetate osteoarthritis rats. Overall, our findings demonstrate an elevated CaV3.2 expression and enhanced function of primary sensory neuron-T channels in the monosodium iodoacetate osteoarthritis pain. Further study is needed to delineate the importance of dysfunctional primary sensory neuron-CaV3.2 in osteoarthritis pain.
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CHIBA, AKIRA, GÜNTER KÄMPER, and R. K. MURPHEY. "RESPONSE PROPERTIES OF INTERNEURONS OF THE CRICKET CERCAL SENSORY SYSTEM ARE CONSERVED IN SPITE OF CHANGES IN PERIPHERAL RECEPTORS DURING MATURATION." Journal of Experimental Biology 164, no. 1 (March 1, 1992): 205–26. http://dx.doi.org/10.1242/jeb.164.1.205.
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During postembryonic development of the cricket, the total number of filiform hair sensilla in the cereal sensory system increases approximately 40-fold. In addition, individual receptor hairs grow in size, changing the transducer properties of the sensilla and, thereby, the information transmitted to the central nervous system (CNS) by the sensory neurons. Interneurons MGI and 10–3 receive monosynaptic inputs from these sensory neurons and send outputs to anterior ganglia. We show that, in spite of the changes in the periphery, the response properties of these interneurons are relatively constant during development. The two interneurons differ in their frequency response, intensity response and rate of response decrement. Their respective response properties are conserved during the postembryonic period. The results suggest that systematic rearrangement of the sensory neuron-to-interneuron synapses plays an important role in maintaining a constant output of this sensory system to higher centers of the CNS during maturation of the cricket.
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Ciotu, Cosmin I., and Michael J. M. Fischer. "Novel Analgesics with Peripheral Targets." Neurotherapeutics 17, no. 3 (July 2020): 784–825. http://dx.doi.org/10.1007/s13311-020-00937-z.
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Abstract A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics.
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Walters, Marie C., and David R. Ladle. "Calcium homeostasis in parvalbumin DRG neurons is altered after sciatic nerve crush and sciatic nerve transection injuries." Journal of Neurophysiology 126, no. 6 (December 1, 2021): 1948–58. http://dx.doi.org/10.1152/jn.00707.2020.
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This study examines calcium homeostasis after peripheral nerve injury in dorsal root ganglion (DRG) neurons expressing parvalbumin, a group of large-diameter afferents primarily consisting of proprioceptors, using two-photon calcium imaging in the intact DRG. Our findings identify aberrant calcium homeostasis as an additional source of sensory neuron dysfunction following peripheral nerve injury, uncover differences between two injury models, and track how these changes develop and resolve over the course of recovery.
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Myers, Allen C., Radhika Kajekar, and Bradley J. Undem. "Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways." American Journal of Physiology-Lung Cellular and Molecular Physiology 282, no. 4 (April 1, 2002): L775—L781. http://dx.doi.org/10.1152/ajplung.00353.2001.
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In the vagal-sensory system, neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) are synthesized nearly exclusively in small-diameter nociceptive type C-fiber neurons. By definition, these neurons are designed to respond to noxious or tissue-damaging stimuli. A common feature of visceral inflammation is the elevation in production of sensory neuropeptides. Little is known, however, about the physiological characteristics of vagal sensory neurons induced by inflammation to produce substance P. In the present study, we show that allergic inflammation of guinea pig airways leads to the induction of substance P and CGRP production in large-diameter vagal sensory neurons. Electrophysiological and anatomical evidence reveals that the peripheral terminals of these neurons are low-threshold Aδ mechanosensors that are insensitive to nociceptive stimuli such as capsaicin and bradykinin. Thus inflammation causes a qualitative change in chemical coding of vagal primary afferent neurons. The results support the hypothesis that during an inflammatory reaction, sensory neuropeptide release from primary afferent nerve endings in the periphery and central nervous system does not require noxious or nociceptive stimuli but may also occur simply as a result of stimulation of low-threshold mechanosensors. This may contribute to the heightened reflex physiology and pain that often accompany inflammatory diseases.
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Inoe, Ana Paula, Francisco Carlos Pereira, Angelo João Stopiglia, and Ciro Ferreira Da-Silva. "Pharmacological immunomodulation enhances peripheral nerve regeneration." Pesquisa Veterinária Brasileira 27, no. 9 (September 2007): 363–69. http://dx.doi.org/10.1590/s0100-736x2007000900002.
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To assess the effect of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine MDP topically administrated on the regenerating peripheral neurons, twelve male C57BL/6J adult mice were equally distributed into three groups. Four mice underwent unilateral sciatic nerve transection and polyethylene tubulization, with a 4mm gap between the proximal and distal nerve stumps and were implanted with collagen + PBS (COL). Other four animals underwent the same surgical procedure but received collagen + MDP (COL/MDP) inside the prosthesis. Four animals were not operated and served as control group (NOR). After 4 weeks, the regenerated nerve cables were processed for total myelinated axon counting and myelinated fiber diameter measurement. The L5 dorsal root ganglion (DRG) was also removed and sectioned for sensory neurons counting and measurement. The results revealed significant difference (p<0.05) in axonal counting among the groups NOR (4,355±32), COL (1,869±289) and COL/MDP (2,430±223). There was a significant reduction in the axonal diameter in the operated groups (COL=3.38µm±1.16 and COL/MDP=3.54µm±1.16) compared to NOR (6.19µm±2.45). No difference was found in the number of DRG neurons between the experimental groups (COL=564±51; COL/MDP=514±56), which presented fewer sensory neurons compared to NOR (1,097±142). Data obtained indicate that locally applied MDP stimulates peripheral nerve regeneration in mice.
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O’Toole, Sean M., Monica M. Ferrer, Jennifer Mekonnen, Haihan Zhang, Yasuyuki Shima, David R. Ladle, and Sacha B. Nelson. "Dicer maintains the identity and function of proprioceptive sensory neurons." Journal of Neurophysiology 117, no. 3 (March 1, 2017): 1057–69. http://dx.doi.org/10.1152/jn.00763.2016.
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Neuronal cell identity is established during development and must be maintained throughout an animal’s life (Fishell G, Heintz N. Neuron 80: 602–612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899–907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359–373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, microRNAs are crucially important for maintaining proprioception. Additionally, this study hints at the larger question of how neurons maintain their functional and molecular specificity.
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Zhu, Jia, Tao Peng, Savahn Chanthaphavong, Sijie Sun, James Trigilio, Lei Jin, Julio Vazquez, et al. "IL-17c promotes peripheral nerve growth during human herpes simplex virus type 2 (HSV-2) infection." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 61.9. http://dx.doi.org/10.4049/jimmunol.198.supp.61.9.
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Abstract During human HSV-2 infection, peripheral nerve destruction and sensory anesthesia are rarely developed, despite frequent virus reactivation. The mechanisms underlying this clinical observation are unclear. Here, we describe a novel interaction between HSV infected keratinocytes and the peripheral nerve system via IL-17c that promotes neurite growth and neuron survival during reactivations. Skin biopsies obtained during asymptomatic human HSV-2 reactivation exhibit a higher nerve fiber density in relation to biopsies obtained during the virological and clinical quiescent phase. Keratinocytes, the peripheral targets of HSV reactivation, produce IL-17c both in vivo during HSV-2 reactivation in humans and in vitro in primary cultures. Further characterization indicates that IL17RE, the receptor specific for IL-17c signaling, is expressed on nerve endings in human skin and on nerve fibers, glia cells and sensory neurons in human dorsal root ganglia. The addition of exogenous human IL-17c promotes neurite growth and branching and provides directional guidance in a microfluidic device. Furthermore, pretreatment of IL-17c reduces apoptosis in HSV-2 infected primary neurons. Taken together, these results suggest that IL-17c might function as a neurotrophic factor to induce peripheral nerve ending growth and protect neurons from apoptosis during HSV reactivation. This interaction provides a potential mechanism for the lack of clinical nerve damage from a lifelong recurrent neurotropic viral infection. It also highlights the role of immune cytokines in regulating the functions of the peripheral nervous system.
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Bonalume, Veronica, Lucia Caffino, Luca F. Castelnovo, Alessandro Faroni, Flavio Giavarini, Sheng Liu, Donatella Caruso, et al. "Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons." Cells 9, no. 8 (August 11, 2020): 1874. http://dx.doi.org/10.3390/cells9081874.
Full textAbstract:
Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKCε, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKCε via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain.
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Cobo, Ramón, Jorge García-Piqueras, Yolanda García-Mesa, Jorge Feito, Olivia García-Suárez, and Jose A. Vega. "Peripheral Mechanobiology of Touch—Studies on Vertebrate Cutaneous Sensory Corpuscles." International Journal of Molecular Sciences 21, no. 17 (August 27, 2020): 6221. http://dx.doi.org/10.3390/ijms21176221.
Full textAbstract:
The vertebrate skin contains sensory corpuscles that are receptors for different qualities of mechanosensitivity like light brush, touch, pressure, stretch or vibration. These specialized sensory organs are linked anatomically and functionally to mechanosensory neurons, which function as low-threshold mechanoreceptors connected to peripheral skin through Aβ nerve fibers. Furthermore, low-threshold mechanoreceptors associated with Aδ and C nerve fibers have been identified in hairy skin. The process of mechanotransduction requires the conversion of a mechanical stimulus into electrical signals (action potentials) through the activation of mechanosensible ion channels present both in the axon and the periaxonal cells of sensory corpuscles (i.e., Schwann-, endoneurial- and perineurial-related cells). Most of those putative ion channels belong to the degenerin/epithelial sodium channel (especially the family of acid-sensing ion channels), the transient receptor potential channel superfamilies, and the Piezo family. This review updates the current data about the occurrence and distribution of putative mechanosensitive ion channels in cutaneous mechanoreceptors including primary sensory neurons and sensory corpuscles.
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Kalpachidou, Theodora, Lisa Spiecker, Michaela Kress, and Serena Quarta. "Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons." Cells 8, no. 6 (June 15, 2019): 591. http://dx.doi.org/10.3390/cells8060591.
Full textAbstract:
Numerous experimental studies demonstrate that the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases) Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42) are important regulators in somatosensory neurons, where they elicit changes in the cellular cytoskeleton and are involved in diverse biological processes during development, differentiation, survival and regeneration. This review summarizes the status of research regarding the expression and the role of the Rho GTPases in peripheral sensory neurons and how these small proteins are involved in development and outgrowth of sensory neurons, as well as in neuronal regeneration after injury, inflammation and pain perception. In sensory neurons, Rho GTPases are activated by various extracellular signals through membrane receptors and elicit their action through a wide range of downstream effectors, such as Rho-associated protein kinase (ROCK), phosphoinositide 3-kinase (PI3K) or mixed-lineage kinase (MLK). While RhoA is implicated in the assembly of stress fibres and focal adhesions and inhibits neuronal outgrowth through growth cone collapse, Rac1 and Cdc42 promote neuronal development, differentiation and neuroregeneration. The functions of Rho GTPases are critically important in the peripheral somatosensory system; however, their signalling interconnections and partially antagonistic actions are not yet fully understood.
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Hasty, Jeff, J. J. Collins, Kurt Wiesenfeld, and Peter Grigg. "Wavelets of Excitability in Sensory Neurons." Journal of Neurophysiology 86, no. 4 (October 1, 2001): 2097–101. http://dx.doi.org/10.1152/jn.2001.86.4.2097.
Full textAbstract:
We have investigated variations in the excitability of mammalian cutaneous mechanoreceptor neurons. We focused on the phase dynamics of an action potential relative to a periodic stimulus, showing that the excitability of these sensory neurons has interesting nonstationary oscillations. Using a wavelet analysis, these oscillations were characterized through the depiction of their period as a function of time. It was determined that the induced oscillations are weakly dependent on the stimulus frequency, and that lower temperatures significantly reduce the frequency of the phase response. Our results reveal novel excitability properties in sensory neurons, and, more generally, could prove significant in the deduction of mechanistic attributes underlying the nonstationary excitability in neuronal systems. Since peripheral neurons feed information to the CNS, variable responses observed in higher regions may be generated in part at the site of sensory detection.