scholarly journals Sensitization of Cutaneous Primary Afferents in Bone Cancer Revealed by In Vivo Calcium Imaging

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3491
Author(s):  
Larissa de Clauser ◽  
Ana P. Luiz ◽  
Sonia Santana-Varela ◽  
John N. Wood ◽  
Shafaq Sikandar
Keyword(s):  
Bone Marrow ◽  
Dorsal Root Ganglia ◽  
Calcium Imaging ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Cutaneous Afferents ◽  
Retrograde Labelling ◽  
Nociceptive Neurons ◽  
In Vivo Calcium Imaging

Cancer-induced bone pain (CIBP) is a complex condition, comprising components of inflammatory and neuropathic processes, but changes in the physiological response profiles of bone-innervating and cutaneous afferents remain poorly understood. We used a combination of retrograde labelling and in vivo calcium imaging of bone marrow-innervating dorsal root ganglia (DRG) neurons to determine the contribution of these cells in the maintenance of CIBP. We found a majority of femoral bone afferent cell bodies in L3 dorsal root ganglia (DRG) that also express the sodium channel subtype Nav1.8—a marker of nociceptive neurons—and lack expression of parvalbumin—a marker for proprioceptive primary afferents. Surprisingly, the response properties of bone marrow afferents to both increased intraosseous pressure and acid were unchanged by the presence of cancer. On the other hand, we found increased excitability and polymodality of cutaneous afferents innervating the ipsilateral paw in cancer bearing animals, as well as a behavioural phenotype that suggests changes at the level of the DRG contribute to secondary hypersensitivity. This study demonstrates that cutaneous afferents at distant sites from the tumour bearing tissue contribute to mechanical hypersensitivity, highlighting these cells as targets for analgesia.

scholarly journals Sensitization of cutaneous primary afferents in bone cancer revealed by in vivo calcium imaging

2020 ◽  
Author(s):  
Larissa de Clauser ◽  
Ana P. Luiz ◽  
Sonia Santana-Varela ◽  
John N. Wood ◽  
Shafaq Sikandar
Keyword(s):  
Bone Marrow ◽  
Calcium Imaging ◽  
Bone Cancer ◽  
Primary Afferents ◽  
Retrograde Labelling ◽  
Nociceptive Neurons ◽  
Intraosseous Pressure ◽  
Response Profiles ◽  
In Vivo Calcium Imaging

AbstractCancer-induced bone pain (CIBP) is a complex condition comprising components of inflammatory and neuropathic processes, but changes in the physiological response profiles of bone-innervating afferents remain poorly understood. We used a combination of retrograde labelling and in vivo calcium imaging of bone marrow-innervating DRG neurons to determine the contribution of these cells in the establishment and maintenance of CIBP. We found a majority of femoral bone afferent cell bodies in L3 DRG that also express the sodium channel subtype Nav1.8 - a marker of nociceptive neurons- and lack expression of parvalbumin - a marker for proprioceptive primary afferents. Surprisingly, the response properties of bone marrow afferents to both increased intraosseous pressure and acid were unchanged by the presence of cancer. On the other hand, we found increased excitability and polymodality of cutaneous afferents innervating the ipsilateral paw in cancer bearing animals, as well as a behavioral phenotype that suggests changes at the level of the DRG contribute to secondary hypersensitivity.

scholarly journals The Role of Pruriceptors in Enhanced Sensitivities to Pruritogens in a Murine Model of Chronic Compression of Dorsal Root Ganglion

2020 ◽  
Author(s):  
Tao Wang ◽  
Jin Tao ◽  
Yehong Fang ◽  
Chao Ma
Keyword(s):  
Dorsal Root Ganglion ◽  
Calcium Imaging ◽  
Dorsal Root ◽  
Neurological Diseases ◽  
Histamine Receptor ◽  
Drg Neurons ◽  
Itch Sensation ◽  
Chronic Pruritus ◽  
In Vivo Calcium Imaging

Abstract Background: Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure.Methods: In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed DRG. We additionally investigated if pruritogen-evoked activities of dorsal root ganglion (DRG) neurons is enhanced in this model. The expression of TRPV1, CGRP and H1R was detected with immunoflorescent staining. DRG neurons response to four agents using in vivo calcium imaging.Results: Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of algogenic agents including capsaicine and 5-HT, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In vivo calcium imaging revealed that compressed DRG neurons exhibited significantly enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons.Conclusions: Our findings indicated that sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG neurons in mice, and may play a role in chronic pruritus in neurological diseases.

M2-Receptor Subtype Does Not Mediate Muscarine-Induced Increases in [Ca2+]i in Nociceptive Neurons of Rat Dorsal Root Ganglia

2000 ◽  
Vol 84 (4) ◽  
pp. 1934-1941 ◽  
Author(s):  
Rainer Haberberger ◽  
Reas Scholz ◽  
Wolfgang Kummer ◽  
Michaela Kress
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Rt Pcr ◽  
Nociceptive Neurons

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

scholarly journals Automated cellular structure extraction in biological images with applications to calcium imaging data

2018 ◽  
Author(s):  
Gal Mishne ◽  
Ronald R. Coifman ◽  
Maria Lavzin ◽  
Jackie Schiller
Keyword(s):  
Calcium Imaging ◽  
Image Plane ◽  
Cellular Level ◽  
Full Potential ◽  
Imaging Data ◽  
Image Domain ◽  
Biological Images ◽  
Large Populations ◽  
In Vivo Calcium Imaging

AbstractRecent advances in experimental methods in neuroscience enable measuring in-vivo activity of large populations of neurons at cellular level resolution. To leverage the full potential of these complex datasets and analyze the dynamics of individual neurons, it is essential to extract high-resolution regions of interest, while addressing demixing of overlapping spatial components and denoising of the temporal signal of each neuron. In this paper, we propose a data-driven solution to these challenges, by representing the spatiotemporal volume as a graph in the image plane. Based on the spectral embedding of this graph calculated across trials, we propose a new clustering method, Local Selective Spectral Clustering, capable of handling overlapping clusters and disregarding clutter. We also present a new nonlinear mapping which recovers the structural map of the neurons and dendrites, and global video denoising. We demonstrate our approach on in-vivo calcium imaging of neurons and apical dendrites, automatically extracting complex structures in the image domain, and denoising and demixing their time-traces.

scholarly journals A Compact Head-Mounted Endoscope for In Vivo Calcium Imaging in Freely Behaving Mice

2018 ◽  
Vol 84 (1) ◽  
pp. e51 ◽  
Author(s):  
Alexander D. Jacob ◽  
Adam I. Ramsaran ◽  
Andrew J. Mocle ◽  
Lina M. Tran ◽  
Chen Yan ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Freely Behaving ◽  
In Vivo Calcium Imaging

Purinergic signaling between neurons and satellite glial cells of mouse dorsal root ganglia modulates neuronal excitability in vivo

Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Zhiyong Chen ◽  
Qian Huang ◽  
Xiaodan Song ◽  
Neil C. Ford ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Glial Cells ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neuronal Excitability ◽  
Purinergic Signaling ◽  
Satellite Glial Cells

Towards understanding the neural origins of hibernation

2022 ◽  
Vol 225 (1) ◽  
Author(s):  
Madeleine S. Junkins ◽  
Sviatoslav N. Bagriantsev ◽  
Elena O. Gracheva
Keyword(s):  
Nervous System ◽  
Environmental Conditions ◽  
Calcium Imaging ◽  
Essential Role ◽  
Physiological Responses ◽  
Quiescent State ◽  
Physiological Changes ◽  
In Vivo Calcium Imaging

ABSTRACT Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the physiological changes that occur during hibernation have been comprehensively researched, the role of the nervous system in this process remains relatively underexplored. In this Review, we adopt the perspective that the nervous system plays an active, essential role in facilitating and supporting hibernation. Accumulating evidence strongly suggests that the hypothalamus enters a quiescent state in which powerful drives to thermoregulate, eat and drink are suppressed. Similarly, cardiovascular and pulmonary reflexes originating in the brainstem are altered to permit the profoundly slow heart and breathing rates observed during torpor. The mechanisms underlying these changes to the hypothalamus and brainstem are not currently known, but several neuromodulatory systems have been implicated in the induction and maintenance of hibernation. The intersection of these findings with modern neuroscience approaches, such as optogenetics and in vivo calcium imaging, has opened several exciting avenues for hibernation research.

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