Visceral Pain

Schwartz, Erica S.; Gebhart, G. F.

doi:10.1007/7854_2014_315

Cited by 36 publications

(31 citation statements)

References 100 publications

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“…Some of the limitations of this test include lack of specificity as some nonanalgesic drugs also show efficacy. Irritation of nongastrointestinal tissues has also been reported in this model .…”

Section: Models Of Visceral Painsupporting

confidence: 72%

“…These writhing responses include abdominal stretching, flinching, licking, and motor incoordination . For induction of a writhing response in unanesthetized animals, an intraperitoneal injection of dilute acetic acid (0.6–9%V/V) or phenylquinone (0.3–0.9%) is made at a fixed dose (0.2 ml/mouse or 0.5–2.5 ml/rat) or in some cases a weight‐adjusted dose (10 ml/kg) is used . Cytokines , prostaglandins , and bradykinin are all released following intraperitoneal injection of acetic acid and are capable of sensitizing visceral nociceptive afferents.…”

Section: Models Of Visceral Painmentioning

confidence: 99%

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Preclinical Assessment of Inflammatory Pain

2015

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While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.

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Section: Models Of Visceral Painsupporting

confidence: 72%

Section: Models Of Visceral Painmentioning

confidence: 99%

Preclinical Assessment of Inflammatory Pain

2015

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“…The AWR scores were recorded according to previously described criteria (Al-Chaer et al, 2000). The gradually increased pressure was introduced as 20, 40, and 60 mmHg (Schwartz and Gebhart, 2014). In control animals, there was an increased trend in the baseline sensitivity in response to an increased pressure (Figure 7B).…”

Section: Resultsmentioning

confidence: 99%

Regulation of transient receptor potential cation channel subfamily V1 protein synthesis by the phosphoinositide 3-kinase/Akt pathway in colonic hypersensitivity

Shen

Al-Thumairy

Hashmi

et al. 2017

Experimental Neurology

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The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor 1 (VR1), is expressed in nociceptive neurons in the dorsal root ganglia (DRG) and participates in the transmission of pain. The present study investigated the underlying molecular mechanisms by which TRPV1 was regulated by nerve growth factor (NGF) signaling pathways in colonic hypersensitivity in response to colitis. We found that during colitis TRPV1 protein levels were significantly increased in specifically labeled colonic afferent neurons in both L1 and S1 DRGs. TRPV1 protein up-regulation in DRG was also enhanced by NGF treatment. We then found that TRPV1 protein up-regulation in DRG was regulated by activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway both in vivo and in vitro. Suppression of endogenous PI3K/Akt activity during colitis or NGF treatment with a specific PI3K inhibitor LY294002 reduced TRPV1 protein production in DRG neurons, and also reduced colitis-evoked TRPV1-mediated visceral hypersensitivity tested by hyper-responsiveness to colorectal distention (CRD) and von Frey filament stimulation of abdomen. Further studies showed that TRPV1 mRNA levels in the DRG were not regulated by either colitis or NGF. We then found that an up-regulation of the protein synthesis pathway was involved by which both colitis and NGF caused a PI3K-dependent increase in the phosphorylation level of eukaryotic translation initiation factor 4E-binding protein (4E-BP)1. These results suggest a novel mechanism in colonic hypersensitivity which involves PI3K/Akt-mediated TRPV1 protein, not mRNA, up-regulation in primary afferent neurons, likely through activation of the protein synthesis pathways.

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“…These conditions do not respond reliably to analgesics that are commonly administered for somatic pain, indicating that distinct mechanisms underlie their pathobiology. Healthy visceral sensory neurons also have distinct functional properties that underlie encoding of a wide range of changes within organs (Robinson and Gebhart, 2008;Sikandar and Dickenson, 2012;Schwartz and Gebhart, 2014;Gebhart and Bielefeldt, 2016). We are unaware of many of these internal changes, contrasting with our conscious awareness of somatic sensations such as heat, cold, touch, and vibration.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially leading to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively of somatic sensory neurons. This was performed in adult and E18.5 male and female mice. By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal levels. We identified many novel genes that had not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.In this study of mouse dorsal root ganglia (DRG), we have identified numerous features of sensory neurons that vary between lumbar and sacral spinal levels and that are potentially involved in unique physiology and pathophysiology of visceral sensation and pain. We further identify maturational components of this sacral visceral transcriptome by comparing data from embryonic and adult mice. There are limited sex differences across the transcriptome of embryonic or adult sensory ganglia, but in adults these can be revealed in sacral levels and especially in Trpv1 nociceptive neurons. These datasets will encourage identification of new tools to modify mature or developing sensory neurons and adult nociceptive pathways.

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Visceral Pain

Cited by 36 publications

References 100 publications

Preclinical Assessment of Inflammatory Pain

Preclinical Assessment of Inflammatory Pain

Regulation of transient receptor potential cation channel subfamily V1 protein synthesis by the phosphoinositide 3-kinase/Akt pathway in colonic hypersensitivity

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

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