Cited by 289Pain Mechanisms and TreatmentsGut microbiota and healthGastrointestinal motility and disorders

Commensal microbiota is fundamental for the development of inflammatory pain

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Amaral, F. A., Sachs, D., Costa, V. V., Fagundes, C. T., Cisalpino, D., Cunha, T. M., Ferreira, S. H., Cunha, F. Q. +5 more·2008·Proceedings of the National Academy of Sciences

Abstract

The ability of an individual to sense pain is fundamental for its capacity to adapt to its environment and to avoid damage. The sensation of pain can be enhanced by acute or chronic inflammation. In the present study, we have investigated whether inflammatory pain, as measured by hypernociceptive responses, was modified in the absence of the microbiota. To this end, we evaluated mechanical nociceptive responses induced by a range of inflammatory stimuli in germ-free and conventional mice. Our experiments show that inflammatory hypernociception induced by carrageenan, lipopolysaccharide, TNF-α, IL-1β, and the chemokine CXCL1 was reduced in germ-free mice. In contrast, hypernociception induced by prostaglandins and dopamine was similar in germ-free or conventional mice. Reduction of hypernociception induced by carrageenan was associated with reduced tissue inflammation and could be reversed by reposition of the microbiota or systemic administration of lipopolysaccharide. Significantly, decreased hypernociception in germ-free mice was accompanied by enhanced IL-10 expression upon stimulation and could be reversed by treatment with an anti-IL-10 antibody. Therefore, these results show that contact with commensal microbiota is necessary for mice to develop inflammatory hypernociception. These findings implicate an important role of the interaction between the commensal microbiota and the host in favoring adaptation to environmental stresses, including those that cause pain.

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Authors
Amaral, F. A., Sachs, D., Costa, V. V., Fagundes, C. T., Cisalpino, D., Cunha, T. M., Ferreira, S. H., Cunha, F. Q., Silva, T. A., Nicoli, J. R., Vieira, L. Q., Souza, D. G., & Teixeira, M. M.
Affiliations
  • Departments of *Bioquímica e Imunologia and
  • Universidade de São Paulo (BR)
  • Departmento de Patologia Oral, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, CEP 31270-901, Belo Horizonte/MG, Brazil
  • Universidade Federal de Minas Gerais (BR)
Venue
Proceedings of the National Academy of Sciences
Published
2008-02-12
Volume
105
Issue
6
Pages
2193-2197
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2076260247
Cited by
289
References
29
Citations by year
2026: 9 · 2025: 26 · 2024: 24 · 2023: 27 · 2022: 22 · 2021: 24 · 2020: 23 · 2019: 15 · 2018: 13 · 2017: 12 · 2016: 15 · 2015: 15 · 2014: 14 · 2013: 14 · 2012: 11
FWCI
5.64
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
commensal microbiota, inflammatory pain, hypernociception, germ-free mice, carrageenan, lipopolysaccharide, TNF-α, IL-1β, CXCL1, prostaglandins, dopamine, IL-10, host-microbe interactions, mechanical nociception
MeSH terms
Animals, Carrageenan, Germ-Free Life, Hyperalgesia, Inflammation, Interleukin-10, Mice

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