Small Bowel Review: Part II

Thomson, Abr; Hasan, Jesia; Keelan, M.; Wild, G

doi:10.1155/1999/192721

Cited by 8 publications

(7 citation statements)

References 225 publications

(228 reference statements)

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“…This can occur by phosphorylation of the channels [23,139,184,248] or by their insertion or removal from the plasma membrane [47,110,173,200,248]. One novel association between transduction and sensitization is found in a population of nociceptors that, under basal conditions, are mechanically insensitive, and are thus termed mechanically insensitive afferents [36,160] or “silent” nociceptors [88,206], but which, on exposure to inflammatory mediators, develop the ability to respond to mechanical stimulation [197,199]. Given that such mechanically insensitive afferents may play a role in some forms of pain [84,88,107], the mechanisms underlying the development of mechanical transduction of silent nociceptors on exposure to inflammatory mediators remains an important question.…”

Section: The Nociceptor: a Model Cellmentioning

confidence: 99%

The fundamental unit of pain is the cell

Reichling

Green

Levine

2013

Pain

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The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of “pain molecules,” as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.

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Section: The Nociceptor: a Model Cellmentioning

confidence: 99%

The fundamental unit of pain is the cell

Reichling

Green

Levine

2013

Pain

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“…While widely used, the severe dose-limiting side-effects of opioids often results in diminished efficacy 1 . Additionally, opioids carry the risk of abuse and physical dependence, and induce constipation and other unwanted side-effects which diminish quality of life 2, 3 .…”

Section: Introductionmentioning

confidence: 99%

Reversal of Inflammatory and Noninflammatory Visceral Pain by Central or Peripheral Actions of Sumatriptan

et al. 2008

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Background and Aims Sumatriptan is used specifically to relieve headache pain. The possible efficacy of sumatriptan was investigated in two models of visceral pain. Methods Pancreatic inflammation was induced by intravenous injection of dibutyltin dichloride. Non-inflammatory irritable bowel syndrome was induced by intracolonic instillation of sodium butyrate. The effects of systemic sumatriptan on referred hypersensitivity were tested in both models. Effects of sumatriptan within the rostral ventromedial medulla (RVM), a site of descending modulation of visceral pain, was determined by (a) testing the effects of RVM administration of 5HT1B/D antagonists on systemic sumatriptan action and (b) determining whether RVM application of sumatriptan reproduced the actions of systemic drug administration. Results Systemic sumatriptan elicited a dose- and time-related blockade of referred hypersensitivity in both models that was blocked by systemic administration of either 5HT1B or 5HT1D antagonists. Sumatriptan administered into the RVM similarly produced dose- and time-related blockade of referred hypersensitivity in both visceral pain models. This was blocked by local microinjection of the 5HT1B antagonist, but not the 5HT1D antagonist. Microinjection of 5HT1B or 5HT1D antagonists into the RVM did not block the effects of systemic sumatriptan. Conclusions Our findings suggest that sumatriptan suppresses either inflammatory or non-inflammatory visceral pain, most likely through peripheral 5HT1B/1D receptors. Actions at 5HT1B receptors within the RVM offer an additional potential site of action for the modulation of visceral pain by triptans. These studies offer new insights into the development of strategies which may improve therapy of visceral pain conditions using already available medications.

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“…4). Alterations in pain perception in women are thought to involve release of inflammatory mediators and neuropeptides by efferent peripheral nerve endings5, an increase in the sensitivity of nociceptive neurons6, and peripheral hyperalgesia. Continuous input from peripheral afferents can also trigger spinal hyper-excitability (central sensitization)7 resulting in increased pain perception, secondary hyperalgesia and allodynia8.…”

mentioning

confidence: 99%

EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

Greaves

Horne

Jerina

et al. 2017

Sci Rep

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Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.

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Small Bowel Review: Part II

Cited by 8 publications

References 225 publications

The fundamental unit of pain is the cell

The fundamental unit of pain is the cell

Reversal of Inflammatory and Noninflammatory Visceral Pain by Central or Peripheral Actions of Sumatriptan

EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

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