ReferenceID 5494
Common bacterial metabolite indole directly activates nociceptive neuron through transient receptor potential ankyrin 1 channel
Pain
ABSTRACT: Nociceptors are known to directly recognize bacterial cell wall components or secreted toxins, thereby leading to pain induced by bacterial infection. However, direct activation of nociceptors by bacterial meta
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5494
- Evidence Id
- 22084
- Core Evidence Id
- 22084
- Source Reference Id
- 4234
- Herb2 Reference Id
- HBREF005031
- Subject Paper Key
- HBIN030110_34817438
- Pubmed Id
- 34817438
- Doi
- 10.1097/j.pain.0000000000002542
- Paper Title
- Common bacterial metabolite indole directly activates nociceptive neuron through transient receptor potential ankyrin 1 channel
- Paper Abstract
- ABSTRACT: Nociceptors are known to directly recognize bacterial cell wall components or secreted toxins, thereby leading to pain induced by bacterial infection. However, direct activation of nociceptors by bacterial metabolites remains unclear even though bacteria produce numerous metabolites related to health and disease. In the current study, we investigated whether and how a common bacterial metabolite, indole, which is produced by normal microflora of the gastrointestinal (GI) tract and oral cavity, can directly activate nociceptive sensory neurons. We found that indole elicits calcium response and evokes inward currents in subsets of dorsal root ganglia (DRG) neurons. Intraplantar (i.pl.) injection of indole produced nocifensive behaviors in adult mice, which were enhanced in complete Freund's adjuvant (CFA)-induced chronic inflammatory condition. Indole increased calcitonin gene-related peptide (CGRP) release in DRG neurons, and i.pl. injection of indole increased hind paw thickness, suggesting its role in generation of neurogenic inflammation. These in vitro and in vivo indole-induced responses were pharmacologically blocked by transient receptor potential ankyrin 1 (TRPA1) antagonist, HC-030031, and significantly abolished in TRPA1 knockout (KO) mice, indicating that indole targets TRPA1 for its action in DRG neurons. Nocifensive licking behavior induced by the injection of live Escherichia coli was significantly decreased in tryptophanase mutant (TnaA KO) E. coli-injected mice that lack indole production, further supporting the idea that bacteria-derived indole can induce pain during infection. Identifying the mechanism of action of indole through TRPA1 provides insights into bacteria-neuron interactions and the role of bacterial metabolites in pain signaling, especially in inflammation-accompanied bacterial infection.
- Journal
- Pain
- Publish Year
- 2021
- Experiment Subject
- mouse; drg neurons
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Neurogenic Inflammation; Inflammation-accompanied Bacterial Infection; Bacterial Infection; Complete Freund's Adjuvant
- Paper Title Cn
- Paper Title En
- Common bacterial metabolite indole directly activates nociceptive neuron through transient receptor potential ankyrin 1 channel
- Bilingual Status
- semi_complete