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


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.


Microbiota Visceral pain Microbiota/gut/brain axis Probiotic treatment 



Autonomic nervous system


Autistic spectrum disorder


Crohn’s disease


Calcitonin gene-related peptide


Colonic hypersensitivity


Chemotherapy-induced peripheral neuropathy


Central nervous system


Chronic prostatitis


Chronic pelvic pain syndrome


Cytosine guanosine


Dorsal root ganglion


Enterochromaffin cells


Extracellular polymeric matrix


Functional dyspepsia


Fermentable oligo-, di-, monosaccharides and polyols


Fecal microbiota transplantation


Formyl peptide receptor


Gamma-amino butyric acid




G-coupled receptor 41


Histone deacetylase




Interstitial cystitis




Inflammatory bowel disease


Irritable bowel syndrome




Ly6/Plaur domain-containing 8


Lipoteichoic acid


Microbial anti-inflammatory molecule


Mitogen-activated protein kinases


Nuclear factor-κB


NOD-like receptor


Nucleotide oligomerization domain receptor


Pathogen-associated molecular pattern




Post-infectious IBS


Pattern recognition receptor


Polysaccharide A


Short-chain fatty acid


Toll/interleukin-1 receptor


Toll-like receptor


Tumor necrosis factor


Transient receptor potential channel


Transient receptor potential ankyrin member 1


Transient receptor potential melastatin member 3


Transient receptor potential melastatin member 8


Transient receptor potential vanilloid member 1


Transient receptor potential vanilloid member 4


Ulcerative colitis


5-hydroxytryptamine or serotonin


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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