ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1).The American journal of gastroenterology · 2020Trial
- Electroacupuncture inhibits the interaction between peripheral TRPV1 and P2X3 in rats with different pathological pain.Physiological research · 2021Article
- Computational Modeling of Mouse Colorectum Capturing Longitudinal and Through-thickness Biomechanical Heterogeneity.Journal of the mechanical behavior of biomedical materials · 2021Article
- Unique Molecular Characteristics of Visceral Afferents Arising from Different Levels of the Neuraxis: Location of Afferent Somata Predicts Function and Stimulus Detection Modalities.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Visceral pain from colon and rectum: the mechanotransduction and biomechanics.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Load-bearing function of the colorectal submucosa and its relevance to visceral nociception elicited by mechanical stretch.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- AAV-Mediated Gene Delivery to the Enteric Nervous System by Intracolonic Injection.Methods in molecular biology (Clifton, N.J.) · 2019Article
- TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder.Scientific reports · 2018Article
- Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury.Biology of sex differences · 2018Article
- Spinal Afferent Innervation of the Colon and Rectum.Frontiers in cellular neuroscience · 2018Article
- Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Article
- Long-term upregulation of cortical glutamatergic AMPA receptors in a mouse model of chronic visceral pain.Molecular brain · 2015Article
- Article
- The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.Science translational medicine · 2015Article
- Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings.Journal of neurophysiology · 2015Article
- In vitro functional characterization of mouse colorectal afferent endings.Journal of visualized experiments : JoVE · 2015Article
- Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia.Neurobiology of disease · 2014Article
- Article
- The interaction between P2X3 and TRPV1 in the dorsal root ganglia of adult rats with different pathological pains.Molecular painArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity.
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