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Microbiota: a novel regulator of pain

  • Manon Defaye
  • Sandie Gervason
  • Christophe Altier
  • Jean-Yves Berthon
  • Denis Ardid
  • Edith Filaire
  • Frédéric Antonio CarvalhoEmail author
Neurology and Preclinical Neurological Studies - Review Article

Abstract

Among the various regulators of the nervous system, the gut microbiota has been recently described to have the potential to modulate neuronal cells activation. While bacteria-derived products can induce aversive responses and influence pain perception, recent work suggests that “abnormal” microbiota is associated with neurological diseases such as Alzheimer’s, Parkinson’s disease or autism spectrum disorder (ASD). Here we review how the gut microbiota modulates afferent sensory neurons function and pain, highlighting the role of the microbiota/gut/brain axis in the control of behaviors and neurological diseases. We outline the changes in gut microbiota, known as dysbiosis, and their influence on painful gastrointestinal disorders. Furthermore, both direct host/microbiota interaction that implicates activation of “pain-sensing” neurons by metabolites, or indirect communication via immune activation is discussed. Finally, treatment options targeting the gut microbiota, including pre- or probiotics, will be proposed. Further studies on microbiota/nervous system interaction should lead to the identification of novel microbial ligands and host receptor-targeted drugs, which could ultimately improve chronic pain management and well-being.

Keywords

Microbiota Visceral pain Microbiota/gut/brain axis Probiotic treatment 

Abbreviations

ANS

Autonomic nervous system

ASD

Autistic spectrum disorder

CD

Crohn’s disease

CGRP

Calcitonin gene-related peptide

CHS

Colonic hypersensitivity

CIPN

Chemotherapy-induced peripheral neuropathy

CNS

Central nervous system

CP

Chronic prostatitis

CPPS

Chronic pelvic pain syndrome

CpG

Cytosine guanosine

DRG

Dorsal root ganglion

EC

Enterochromaffin cells

EPM

Extracellular polymeric matrix

FD

Functional dyspepsia

FODMAPs

Fermentable oligo-, di-, monosaccharides and polyols

FMT

Fecal microbiota transplantation

FPR

Formyl peptide receptor

GABA

Gamma-amino butyric acid

GF

Germ-free

GPR41

G-coupled receptor 41

HDAc

Histone deacetylase

HPA

Hypothalamic/pituitary/adrenal

IC

Interstitial cystitis

IL

Interleukin

IBD

Inflammatory bowel disease

IBS

Irritable bowel syndrome

LPS

Lipopolysaccharide

Lypd8

Ly6/Plaur domain-containing 8

LTA

Lipoteichoic acid

MAM

Microbial anti-inflammatory molecule

MAPKs

Mitogen-activated protein kinases

NF-κB

Nuclear factor-κB

NLR

NOD-like receptor

NOD

Nucleotide oligomerization domain receptor

PAMP

Pathogen-associated molecular pattern

PGN

Peptidoglycan

PI-IBS

Post-infectious IBS

PRRs

Pattern recognition receptor

PSA

Polysaccharide A

SCFA

Short-chain fatty acid

TIR

Toll/interleukin-1 receptor

TLR

Toll-like receptor

TNF

Tumor necrosis factor

TRP

Transient receptor potential channel

TRPA1

Transient receptor potential ankyrin member 1

TRPM3

Transient receptor potential melastatin member 3

TRPM8

Transient receptor potential melastatin member 8

TRPV1

Transient receptor potential vanilloid member 1

TRPV4

Transient receptor potential vanilloid member 4

UC

Ulcerative colitis

5-HT

5-hydroxytryptamine or serotonin

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Manon Defaye
    • 1
  • Sandie Gervason
    • 2
    • 3
  • Christophe Altier
    • 1
  • Jean-Yves Berthon
    • 2
  • Denis Ardid
    • 3
  • Edith Filaire
    • 2
    • 4
  • Frédéric Antonio Carvalho
    • 3
    Email author
  1. 1.Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.GREENTECH SASaint-BeauzireFrance
  3. 3.Université Clermont Auvergne, INSERM U1107, NeuroDol, CRHN AuvergneClermont-FerrandFrance
  4. 4.Université Clermont Auvergne, INRA, Unité de Nutrition Humaine ECREIN, CRNH AuvergneClermont-FerrandFrance

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