The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Jones, Rhys Bevan; Xu, Honghui; Gebhart, G. F.

doi:10.1523/jneurosci.0703-05.2005

Cited by 383 publications

(335 citation statements)

References 35 publications

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“…It is interesting to know whether such mechanotransduction is pH-dependent or independent. In this regard, the recent discovery of novel nonproton ligands (13) raises the possibility that ASIC3-dependent mechanosensation (45,66,70) may be mediated by as yet unknown ligands induced by mechanical stimuli. ASIC3 has intrinsic osmosensitivity, which might underlie systematic osmoregulation.…”

Section: Discussionmentioning

confidence: 99%

“…Jones et al (70) assessed the visceral nociception, modeled by the visceromotor response to colorectal distension and colon afferent fiber mechanosensitivity, in control mice and two congenic knockout mouse strains with deletions of either TRPV1 or ASIC3. They found that both TRPV1 and ASIC3 knockout mice were significantly less sensitive to distension, with an average response magnitude of only about 58% and 50% of the WT controls, respectively.…”

Section: Visceral Nociceptionmentioning

confidence: 99%

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ASIC3 Channels in Multimodal Sensory Perception

2010

ACS Chem. Neurosci.

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Acid-sensing ion channels (ASICs), which are members of the sodium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/ DEG) family, act as membrane-bound receptors for extracellular protons as well as nonproton ligands. At least five ASIC subunits have been identified in mammalian neurons, which form both homotrimeric and heterotrimeric channels. The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. Different from other ASIC subunit composing ion channels, ASIC3 channels can mediate a sustained window current in response to mild extracellular acidosis (pH 7.3-6.7), which often occurs accompanied by many sensory stimuli. Furthermore, recent evidence indicates that the sustained component of ASIC3 currents can be enhanced by nonproton ligands including the endogenous metabolite agmatine. In this review, we first summarize the growing body of evidence for the involvement of ASIC3 channels in multimodal sensory perception and then discuss the potential mechanisms underlying ASIC3 activation and mediation of sensory perception, with a special emphasis on its role in nociception. We conclude that ASIC3 activation and modulation by diverse sensory stimuli represent a new avenue for understanding the role of ASIC3 channels in sensory perception. Furthermore, the emerging implications of ASIC3 channels in multiple sensory dysfunctions including nociception allow the development of new pharmacotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Visceral Nociceptionmentioning

confidence: 99%

ASIC3 Channels in Multimodal Sensory Perception

2010

ACS Chem. Neurosci.

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“…These changes in ASIC3 current should increase acid-induced excitation of ASIC3 neurons and increase the number of neurons responding to acid. ASIC3−/− mice are significantly less responsive to colorectal distension, an indicator of visceral nociception, with an average response magnitude of only 50% that of C57BL/6J mice (Jones et al, 2005). Further, enhancement of stretch-evoked afferent fiber responses in control mice evoked by inflammatory mediators is impaired in ASIC3−/− mice compared to C57BL/6J mice (Jones et al, 2005), suggesting a role for ASIC3 in visceral nociception.…”

Section: Acid Pain and Asicsmentioning

confidence: 94%

“…ASIC3 is a member of the DEG/ ENaC family that is known to mediate mechanical responsiveness in Caenorhabditis elegens including those sensations related to deep tissue, proprioception and muscle stretch (Driscoll and Chalfie, 1991;Huang and Chalfie, 1994;Liu et al, 1996;Tavernarakis et al, 1997). Further, ASIC3 plays a role in normal visceral mechanosensation to stretch and in mechanical sensitization of primary afferents after visceral inflammation (Jones et al, 2005). In contrast, TRPV1 appears to mediate heat hyperalgesia associated with inflammation (Keeble et al, 2005;Honore et al, 2005;Caterina et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation

Sluka

Radhakrishnan

Benson

et al. 2007

Pain

166

160

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Peripheral initiators of muscle pain are virtually unknown, but likely key to development of chronic pain after muscle insult. The current study tested the hypothesis that ASIC3 in muscle is necessary for development of cutaneous mechanical, but not heat hyperalgesia induced by muscle inflammation. Using mechanical and heat stimuli, we assessed behavioral responses in ASIC3−/− and ASIC3+/+ mice after induction of carrageenan muscle inflammation. ASIC3−/−mice did not develop cutaneous mechanical hyperalgesia after muscle inflammation when compared to ASIC3+/ + mice; heat hyperalgesia developed similarly between groups. We then tested if the phenotype could be rescued in ASIC3−/− mice by using a recombinant herpes virus vector to express ASIC3 in skin (where testing occurred) or muscle (where inflammation occurred). Infection of mouse DRG neurons with ASIC3-encoding virus resulted in functional expression of ASICs. Injection of ASIC3-encoding virus into muscle or skin of ASIC3−/− mice resulted in ASIC3 mRNA in DRG and protein expression in DRG and the peripheral injection site. Injection of ASIC3-encoding virus into muscle, but not skin, resulted in development of mechanical hyperalgesia similar to that observed in ASIC3+/+ mice. Thus, ASIC3 in primary afferent fibers innervating muscle is critical to development of hyperalgesia that results from muscle insult.

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“…These afferent nerves respond linearly to increasing levels of distension and signal into the noxious range. They also express putative nociceptive channels, including members of the Transient Receptor Potential (TRPV1, TRPA1) and Acid Sensing Ion Channel 6 (ASIC3) families, implying they act as intensity encoders and modulate the sensory processing of pain (Brierley et al, 2009;Brookes et al, 2013;Gebhart, 2000;Jones et al, 2005). Immune derived mediators are known to excite viscerosensory nerves and have previously been implicated in the heightened sensitivity to distension of the colo-rectum experienced by IBS patients (Hughes et al, 2009a;Hughes et al, 2013b).…”

Section: Introductionmentioning

confidence: 99%

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Cited by 383 publications

References 35 publications

ASIC3 Channels in Multimodal Sensory Perception

ASIC3 Channels in Multimodal Sensory Perception

ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

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