期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02448-6
关键词
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资金
- National Institute of Health (NIH) under NCCIH [DP2AT009499]
- National Institute of Health (NIH) under NIAID [K22AI114810, T32 AI007180, F30 AI124606, R01 AI105129, R01 AI099394, R01 AI121244]
- National Institute of Health (NIH) under NIGMS [T32 GM007308]
- National Institute of Health (NIH) under Intramural Research Program of the NIAID
- National Institutes of Health (NIH) under NIH ZIA [AI000904]
- National Institutes of Health (NIH) under NINDS [NS039518]
- National Institutes of Health (NIH) under DoD [W81XWH-15-1-0480]
- Kaneb fellowship award
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD090255] Funding Source: NIH RePORTER
- National Center for Complementary & Integrative Health [DP2AT009499] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K22AI114810, ZIAAI000904, T32AI007180, R01AI105129, R01AI130019, R01AI121244, F30AI124606, R01AI099394] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007308] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS039518, R37NS039518] Funding Source: NIH RePORTER
The hallmark of many bacterial infections is pain. The underlying mechanisms of pain during live pathogen invasion are not well understood. Here, we elucidate key molecular mechanisms of pain produced during live methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that spontaneous pain is dependent on the virulence determinant agr and bacterial pore-forming toxins (PFTs). The cation channel, TRPV1, mediated heat hyperalgesia as a distinct pain modality. Three classes of PFTs-alpha-hemolysin (Hla), phenol-soluble modulins (PSMs), and the leukocidin HlgAB-directly induced neuronal firing and produced spontaneous pain. From these mechanisms, we hypothesized that pores formed in neurons would allow entry of the membrane-impermeable sodium channel blocker QX-314 into nociceptors to silence pain during infection. QX-314 induced immediate and long-lasting blockade of pain caused by MRSA infection, significantly more than lidocaine or ibuprofen, two widely used clinical analgesic treatments.
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