The Role of the Gastrointestinal Microbiota in Visceral Pain

2016 ◽  
pp. 269-287 ◽  
Author(s):  
Kieran Rea ◽  
Siobhain M. O’Mahony ◽  
Timothy G. Dinan ◽  
John F. Cryan
Keyword(s):  
Visceral Pain ◽  
Gastrointestinal Microbiota

scholarly journals A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

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

scholarly journals Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas
Keyword(s):  
Action Potentials ◽  
Channel Blocker ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Afferent Neurons ◽  
Sodium Channel Blocker ◽  
Voltage Gated Sodium Channels ◽  
New Strategy ◽  
Specific Receptors

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

scholarly journals Animal models of visceral pain and the role of the microbiome

2021 ◽  
pp. 100064
Author(s):  
Christine West ◽  
Karen-Anne McVey Neufeld
Keyword(s):  
Animal Models ◽  
Visceral Pain

scholarly journals Acupuncture for Primary Dysmenorrhea: A Potential Mechanism from an Anti-Inflammatory Perspective

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wen-Yan Yu ◽  
Liang-Xiao Ma ◽  
Zhou Zhang ◽  
Jie-Dan Mu ◽  
Tian-Yi Sun ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Animal Studies ◽  
Visceral Pain ◽  
Self Healing ◽  
Primary Dysmenorrhea ◽  
Potential Mechanism ◽  
Future Studies ◽  
Anti Inflammatory ◽  
Proinflammatory Factors

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women’s overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

scholarly journals Visceral pain: role of the microbiome-gut-brain axis

2017 ◽  
Vol 39 (2) ◽  
pp. 6-9
Author(s):  
Kieran Rea ◽  
Siobhain M. O' Mahony ◽  
Timothy G. Dinan ◽  
John F. Cryan
Keyword(s):  
Cell Activation ◽  
Visceral Pain ◽  
Radical Change ◽  
Bioactive Molecules ◽  
Gastrointestinal Microbiome ◽  
Emotional Behaviour ◽  
Microbial Environment ◽  
Central Level ◽  
Pituitary Adrenal Axis

A growing body of preclinical and clinical evidence supports a relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiome) and health status. These microbes can influence centrally regulated emotional behaviour through mechanisms including microbially derived bioactive molecules, mucosal immune and enteroendocrine cell activation, as well as vagal nerve stimulation. Changes to the microbial environment, as a consequence of illness, stress or injury can lead to a broad spectrum of local physiological and behavioural effects including a decrease in gut barrier integrity, altered gut motility, inflammatory mediator release, as well as nociceptive and distension receptor sensitization. Impacts at a central level include alterations in the hypothalamic-pituitary-adrenal axis, neuroinflammatory events and concomitant changes to neurotransmitter systems. Thus, both central and peripheral pathways associated with pain manifestation and perception are altered as a consequence of the microbiome-gut-brain axis imbalance. The dogmatic approach of antibiotic treatment in the latter century, for the treatment of many diseases and conditions, has undergone a radical change. We are 90% microbe, and pragmatism suggests that we manipulate this ecosystem for the treatment of various ailments, stress dysfunction and affective disorders, including the alleviation of visceral pain.

scholarly journals Peripheral aetiopathogenic drivers and mediators of Parkinson’s disease and co-morbidities: role of gastrointestinal microbiota

2015 ◽  
Vol 22 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Sylvia M. Dobbs ◽  
R. John Dobbs ◽  
Clive Weller ◽  
André Charlett ◽  
Aisha Augustin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Microbiota

Tachykininergic mediation of viscerosensitive responses to acute inflammation in rats: role of CGRP

1997 ◽  
Vol 272 (1) ◽  
pp. G141-G146 ◽  
Author(s):  
V. Julia ◽  
L. Bueno
Keyword(s):  
Acetic Acid ◽  
Gastric Emptying ◽  
Visceral Pain ◽  
Abdominal Muscle ◽  
Sodium Chromate ◽  
Sensory Afferents ◽  
Neurokinin Receptors ◽  
Calcitonin Gene ◽  
Reconstituted Milk

Tachykinins, colocalized with calcitonin gene-related peptides (CGRP) in sensory afferents, are involved in viscerosensitive responses. We investigated the role of tachykinins and CGRP in both nociceptive and visceromotor responses to inflammation. Visceral pain was assessed by abdominal muscle contractions. Gastric emptying was evaluated after gavage with reconstituted milk containing 51Cr-labeled sodium chromate. Acetic acid or 9% NaCl was injected intraperitoneally before the meal. RP-67580, SR-48968, human CGRP [hCGRP-(8-37)], or their vehicles were injected before acetic acid or saline. RP-67580, SR-48968, or their vehicles were injected before CGRP and the meal. GR-73632 or GR-76349 was injected before the meal. Acetic acids inhibited gastric emptying and increased the number of abdominal contractions. RP-67580 reduced the inhibition of gastric emptying without affecting the abdominal response. SR-48968 only reduced the acetic acid-induced increase of abdominal contractions. hCGRP-(8-37) reduced both responses induced by acetic acid. CGRP mimicked the effects of acetic acid. RP-67580 abolished CGRP-induced gastric emptying inhibition, whereas SR-48968 only diminished visceral pain. GR-73632 reduced gastric emptying, and GR-64349 increased abdominal response. In inflammation, neurokinin receptors (NK1 and NK2) mediate the gastric emptying inhibition and visceral pain, respectively. These responses involve a release of CGRP.

scholarly journals The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats

2007 ◽  
Vol 120 (20) ◽  
pp. 1813-1819 ◽  
Author(s):  
Donald PISTON ◽  
Shan WANG ◽  
Yi FENG ◽  
Ying-jiang YE ◽  
Jing ZHOU ◽  
...  
Keyword(s):  
Stress Response ◽  
Visceral Pain ◽  
Cyclooxygenase 2
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