Gut microbiota is critical for the induction of chemotherapy-induced pain

Nat Neurosci. 2017 Sep;20(9):1213-1216. doi: 10.1038/nn.4606. Epub 2017 Jul 17.

Abstract

Chemotherapy-induced pain is a dose-limiting condition that affects 30% of patients undergoing chemotherapy. We found that gut microbiota promotes the development of chemotherapy-induced mechanical hyperalgesia. Oxaliplatin-induced mechanical hyperalgesia was reduced in germ-free mice and in mice pretreated with antibiotics. Restoring the microbiota of germ-free mice abrogated this protection. These effects appear to be mediated, in part, by TLR4 expressed on hematopoietic cells, including macrophages.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cells, Cultured
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / metabolism*
  • Hyperalgesia / microbiology
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Pain / chemically induced*
  • Pain / metabolism*
  • Pain / microbiology
  • Pain Measurement / methods
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Inflammation Mediators
  • Organoplatinum Compounds
  • Oxaliplatin