Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis

Over 60% of women with endometriosis experience abdominopelvic pain and broader pain manifestations, including chronic back pain, fibromyalgia, chronic fatigue, vulvodynia, and migraine. Although the imbalance of proinflammatory mediators, including the complement component C5a, is associated with e...

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Vydáno v:	Nature communications Ročník 15; číslo 1; s. 10142 - 15
Hlavní autoři:	Titiz, Mustafa, Landini, Lorenzo, Souza Monteiro de Araujo, Daniel, Marini, Matilde, Seravalli, Viola, Chieca, Martina, Pensieri, Pasquale, Montini, Marco, De Siena, Gaetano, Pasquini, Benedetta, Vannuccini, Silvia, Iannone, Luigi Francesco, Cunha, Thiago M., Brancolini, Giulia, Bellantoni, Elisa, Scuffi, Irene, Mastricci, Alessandra, Tesi, Martina, Di Tommaso, Mariarosaria, Petraglia, Felice, Geppetti, Pierangelo, Nassini, Romina, De Logu, Francesco
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 25.11.2024 Nature Publishing Group Nature Portfolio
Témata:	13/109 14/32 14/63 42/44 49/88 631/80/304 692/308/1426 692/308/2778 692/308/575 692/700/565/411 82/51 96/1 96/34 96/95 Adaptor Proteins, Signal Transducing Animals Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Back pain Cell activation Chronic pain Complement C5a - metabolism Complement component C5a Disease Models, Animal Endometriosis Endometriosis - metabolism Endometriosis - pathology Fatigue Female Fibromyalgia Headache Humanities and Social Sciences Humans IL-1β Inflammasomes Inflammasomes - metabolism Interleukin-1beta - metabolism Macrophages Macrophages - metabolism Mice Mice, Inbred C57BL Migraine multidisciplinary Nerves Oxidative Stress Pain Pain - metabolism Pain sensitivity Receptor, Anaphylatoxin C5a - genetics Receptor, Anaphylatoxin C5a - metabolism Receptors Schwann cells Schwann Cells - metabolism Science Science (multidisciplinary) Therapeutic targets TRPA1 Cation Channel - genetics TRPA1 Cation Channel - metabolism
ISSN:	2041-1723, 2041-1723
On-line přístup:	Získat plný text
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Shrnutí:	Over 60% of women with endometriosis experience abdominopelvic pain and broader pain manifestations, including chronic back pain, fibromyalgia, chronic fatigue, vulvodynia, and migraine. Although the imbalance of proinflammatory mediators, including the complement component C5a, is associated with endometriosis-related pain, the mechanisms causing widespread pain and the C5a role remain unclear. Female mice and women with endometriosis exhibit increased plasma C5a levels and pain. We hypothesize the Schwann cells involvement in endometriotic pain. Here, we show that silencing the C5a receptor (C5aR1) in Schwann cells blocks the C5a-induced activation of the NLRP1 inflammasome and subsequent release of interleukin-1β (IL-1β). Macrophages, recruited to sciatic/trigeminal nerves by IL-1β from Schwann cells, increase oxidative stress, which activates the proalgesic TRPA1 pathway, resulting in widespread pain. These findings reveal a pathway involving Schwann cell C5aR1, NLRP1/IL-1β activation, macrophage recruitment, oxidative stress, and TRPA1 engagement, contributing to pain in a mouse model of endometriosis. Endometriosis affects over 60% of women, leading to widespread pain. Here, the authors show that blocking C5a receptor (C5aR1) in Schwann cells reduces pain by inhibiting pathways that trigger inflammation, oxidative stress, and nerve sensitivity, revealing a potential therapeutic target in endometriosis pain management.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-54486-6