TRP Channels in Visceral Pain

Visceral pain is both different and similar to somatic pain - different in being poorly localized and usually referred elsewhere to the body wall, but similar in many of the molecular mechanisms it employs (like TRP channels) and the specialization of afferent endings to detect painful stimuli. TRPV1 is sensitive to low pH. pH is lowest in gastric juice, which may cause severe pain when exposed to the oesophageal mucosa, and probably works via TRPV1. TRPV1 is found in afferent fibres throughout the viscera, and the TRPV1 agonist capsaicin can recapitulate symptoms experienced in disease. TRPV1 is also involved in normal mechanosensory function in the gut. Roles for TRPV4 and TRPA1 have also been described in visceral afferents, and TRPV4 is highly enriched in them, where it plays a major role in both mechanonociception and chemonociception. It may provide a visceral-specific nociceptor target for drug development. TRPA1 is also involved in mechano-and chemosensory function, but not as selectively as TRPV4. TRPA1 is colocalized with TRPV1 in visceral afferents, where they influence each other's function. Another modulator of TRPV1 is the cool/mint receptor TRPM8, which, when activated can abrogate responses mediated via TRPV1, suggesting that TRPM8 agonists may provide analgesia via this pathway. In all, the viscera are rich in TRP channel targets on nociceptive neurones which we hope will provide opportunities for therapeutic analgesia.

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Leg development in flies versus grasshoppers: differences in dpp expression do not lead to differences in the expression of downstream components of the leg patterning pathway

Development ◽

10.1242/dev.127.8.1617 ◽

2000 ◽

Vol 127 (8) ◽

pp. 1617-1626 ◽

Cited By ~ 2

Author(s):

E.L. Jockusch ◽

C. Nulsen ◽

S.J. Newfeld ◽

L.M. Nagy

Keyword(s):

Imaginal Disc ◽

Body Wall ◽

Molecular Mechanisms ◽

Current Model ◽

The Body ◽

Genetic Interactions ◽

Leg Development ◽

Evolutionarily Conserved ◽

Early Expression ◽

Two Phases

All insect legs are structurally similar, characterized by five primary segments. However, this final form is achieved in different ways. Primitively, the legs developed as direct outgrowths of the body wall, a condition retained in most insect species. In some groups, including the lineage containing the genus Drosophila, legs develop indirectly from imaginal discs. Our understanding of the molecular mechanisms regulating leg development is based largely on analysis of this derived mode of leg development in the species D. melanogaster. The current model for Drosophila leg development is divided into two phases, embryonic allocation and imaginal disc patterning, which are distinguished by interactions among the genes wingless (wg), decapentaplegic (dpp) and distalless (dll). In the allocation phase, dll is activated by wg but repressed by dpp. During imaginal disc patterning, dpp and wg cooperatively activate dll and also indirectly inhibit the nuclear localization of Extradenticle (Exd), which divide the leg into distal and proximal domains. In the grasshopper Schistocerca americana, the early expression pattern of dpp differs radically from the Drosophila pattern, suggesting that the genetic interactions that allocate the leg differ between the two species. Despite early differences in dpp expression, wg, Dll and Exd are expressed in similar patterns throughout the development of grasshopper and fly legs, suggesting that some aspects of proximodistal (P/D) patterning are evolutionarily conserved. We also detect differences in later dpp expression, which suggests that dpp likely plays a role in limb segmentation in Schistocerca, but not in Drosophila. The divergence in dpp expression is surprising given that all other comparative data on gene expression during insect leg development indicate that the molecular pathways regulating this process are conserved. However, it is consistent with the early divergence in developmental mode between fly and grasshopper limbs.

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Asexual Reproduction in Holothurians

The Scientific World JOURNAL ◽

10.1155/2014/527234 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 13

Author(s):

Igor Yu. Dolmatov

Keyword(s):

Asexual Reproduction ◽

Body Wall ◽

Molecular Mechanisms ◽

Basic Mechanism ◽

The Body ◽

Cross Link ◽

Additional Species ◽

Reproduction Mode ◽

History Of ◽

Anterior Posterior

Aspects of asexual reproduction in holothurians are discussed. Holothurians are significant as fishery and aquaculture items and have high commercial value. The last review on holothurian asexual reproduction was published 18 years ago and included only 8 species. An analysis of the available literature shows that asexual reproduction has now been confirmed in 16 holothurian species. Five additional species are also most likely capable of fission. The recent discovery of new fissiparous holothurian species indicates that this reproduction mode is more widespread in Holothuroidea than previously believed. New data about the history of the discovery of asexual reproduction in holothurians, features of fission, and regeneration of anterior and posterior fragments are described here. Asexual reproduction is obviously controlled by the integrated systems of the organism, primarily the nervous system. Special molecular mechanisms appear to determine the location where fission occurs along the anterior-posterior axis of the body. Alteration of the connective tissue strength of the body wall may play an important role during fission of holothurians. The basic mechanism of fission is the interaction of matrix metalloproteinases, their inhibitors, and enzymes forming cross-link complexes between fibrils of collagen. The population dynamics of fissiparous holothurians are discussed.

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Pathobiology of Visceral Pain: Molecular Mechanisms and Therapeutic Implications V. Central nervous system processing of somatic and visceral sensory signals

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.1.g1 ◽

2000 ◽

Vol 279 (1) ◽

pp. G1-G6 ◽

Cited By ~ 21

Author(s):

Uri Ladabaum ◽

Satoshi Minoshima ◽

Chung Owyang

Keyword(s):

Molecular Mechanisms ◽

Pain Perception ◽

Visceral Pain ◽

Imaging Techniques ◽

Functional Brain Imaging ◽

Anterior Cingulate ◽

Visceral Sensation ◽

Therapeutic Implications ◽

Somatic Pain ◽

Dimensions Of Pain

Somatic and visceral sensation, including pain perception, can be studied noninvasively in humans with functional brain imaging techniques. Positron emission tomography and functional magnetic resonance imaging have identified a series of cerebral regions involved in the processing of somatic pain, including the anterior cingulate, insular, prefrontal, inferior parietal, primary and secondary somatosensory, and primary motor and premotor cortices, the thalamus, hypothalamus, brain stem, and cerebellum. Experimental evidence supports possible specific roles for individual structures in processing the various dimensions of pain, such as encoding of affect in the anterior cingulate cortex. Visceral sensation has been examined in the setting of myocardial ischemia, distension of hollow viscera, and esophageal acidification. Although knowledge regarding somatic sensation is more extensive than the information available for visceral sensation, important similarities have emerged between cerebral representations of somatic and visceral pain.

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Analysis of the gene transcription patterns and DNA methylation characteristics of triploid sea cucumbers (Apostichopus japonicus)

Scientific Reports ◽

10.1038/s41598-021-87278-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingshu Han ◽

Yi Sun ◽

Yue Cao ◽

Pingping Gao ◽

Zijiao Quan ◽

...

Keyword(s):

Dna Methylation ◽

Body Wall ◽

Molecular Mechanisms ◽

Apostichopus Japonicus ◽

Economic Benefits ◽

Methylation Pattern ◽

The Body ◽

Aquatic Animal ◽

Sea Cucumbers ◽

Differentially Methylated Genes

AbstractBreeding of polyploid aquatic animals is still an important approach and research hotspot for realizing the economic benefits afforded by the improvement of aquatic animal germplasm. To better understand the molecular mechanisms of the growth of triploid sea cucumbers, we performed gene expression and genome-wide comparisons of DNA methylation using the body wall tissue of triploid sea cucumbers using RNA-seq and MethylRAD-seq technologies. We clarified the expression pattern of triploid sea cucumbers and found no dosage effect. DEGs were significantly enriched in the pathways of nucleic acid and protein synthesis, cell growth, cell division, and other pathways. Moreover, we characterized the methylation pattern changes and found 615 differentially methylated genes at CCGG sites and 447 differentially methylated genes at CCWGG sites. Integrative analysis identified 23 genes (such as Guf1, SGT, Col5a1, HAL, HPS1, etc.) that exhibited correlations between promoter methylation and expression. Altered DNA methylation and expression of various genes suggested their roles and potential functional interactions in the growth of triploid sea cucumbers. Our data provide new insights into the epigenetic and transcriptomic alterations of the body wall tissue of triploid sea cucumbers and preliminarily elucidate the molecular mechanism of their growth, which is of great significance for the breeding of fine varieties of sea cucumbers.

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Lymphangiomatosis of the Body Wall: A Report of Two Cases Associated with Chylothorax and Fatal Outcome

Fetal and Pediatric Pathology ◽

10.3109/15513819709168739 ◽

1997 ◽

Vol 17 (4) ◽

pp. 617-624 ◽

Cited By ~ 1

Author(s):

Philippe Moerman ◽

Chris Van Geet ◽

Hugo Devlieger

Keyword(s):

Body Wall ◽

Fatal Outcome ◽

The Body

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Toxicology

10.1093/oso/9780190662677.003.0007 ◽

2017 ◽

Author(s):

Robert Laumbach ◽

Michael Gochfeld

Keyword(s):

Molecular Mechanisms ◽

Molecular Targets ◽

Toxicity Testing ◽

The Body ◽

Toxic Substances ◽

Basic Principles ◽

Practical Applications ◽

Mechanisms Of Toxicity ◽

Body Distribution ◽

Threshold Doses

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.

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A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.036 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 278-279

Author(s):

M Defaye ◽

N Abdullah ◽

M Iftinca ◽

C Altier

Keyword(s):

Chronic Pain ◽

Central Sensitization ◽

Microglial Activation ◽

Visceral Pain ◽

Purinergic Signaling ◽

Designer Drugs ◽

Visceral Afferents ◽

Peripheral Sensitization ◽

Specific Expression

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship

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A screen for genetic loci required for body-wall muscle development during embryogenesis in Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/137.2.483 ◽

1994 ◽

Vol 137 (2) ◽

pp. 483-498

Author(s):

J Ahnn ◽

A Fire

Keyword(s):

Caenorhabditis Elegans ◽

Myosin Heavy Chain ◽

Muscle Cell ◽

Heavy Chain ◽

Body Wall ◽

Muscle Development ◽

Contractile Function ◽

The Body ◽

Body Wall Muscle ◽

Genetic Loci

Abstract We have used available chromosomal deficiencies to screen for genetic loci whose zygotic expression is required for formation of body-wall muscle cells during embryogenesis in Caenorhabditis elegans. To test for muscle cell differentiation we have assayed for both contractile function and the expression of muscle-specific structural proteins. Monoclonal antibodies directed against two myosin heavy chain isoforms, the products of the unc-54 and myo-3 genes, were used to detect body-wall muscle differentiation. We have screened 77 deficiencies, covering approximately 72% of the genome. Deficiency homozygotes in most cases stain with antibodies to the body-wall muscle myosins and in many cases muscle contractile function is observed. We have identified two regions showing distinct defects in myosin heavy chain gene expression. Embryos homozygous for deficiencies removing the left tip of chromosome V fail to accumulate the myo-3 and unc-54 products, but express antigens characteristic of hypodermal, pharyngeal and neural development. Embryos lacking a large region on chromosome III accumulate the unc-54 product but not the myo-3 product. We conclude that there exist only a small number of loci whose zygotic expression is uniquely required for adoption of a muscle cell fate.

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