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IL-33/ST2 induces macrophage-dependent ROS production and TRPA1 activation that mediate pain-like responses by skin incision in mice.
Xu, Ruoyao; Pan, Yushuang; Zheng, Kaige; Chen, Muyan; Yin, Chengyu; Hu, Qimiao; Wang, Jie; Yu, Qing; Li, Peiyi; Tai, Yan; Fang, Junfan; Liu, Boyu; Fang, Jianqiao; Tian, Guihua; Liu, Boyi.
Afiliación
  • Xu R; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Pan Y; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Zheng K; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Chen M; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Yin C; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Hu Q; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Wang J; Department of Rehabilitation in Traditional Chinese Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • Yu Q; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Li P; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Tai Y; Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • Fang J; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Liu B; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Fang J; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • Tian G; Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
  • Liu B; Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Theranostics ; 14(13): 5281-5302, 2024.
Article en En | MEDLINE | ID: mdl-39267790
ABSTRACT

Background:

Insufficiently managed incisional (INC) pain severely affects patients' life quality and rehabilitation after a major operation. However, mechanisms underlying INC pain still remain poorly understood.

Methods:

A mouse model of INC pain was established by skin plus deep muscle incision. Biochemistry assay, in vivo reactive oxygen species (ROS) imaging, Ca2+ imaging combined with retrograde labelling, neuron tracing and nocifensive behavior test, etc. were utilized for mechanism investigation.

Results:

We found pro-nociceptive cytokine interleukin -33 (IL-33) ranked among top up-regulated cytokines in incised tissues of INC pain model mice. IL-33 was predominantly expressed in keratinocytes around the incisional area. Neutralization of IL-33 or its receptor suppression of tumorigenicity 2 protein (ST2) or genetic deletion of St2 gene (St2 -/-) remarkably ameliorated mechanical allodynia and improved gait impairments of model mice. IL-33 contributes to INC pain by recruiting macrophages, which subsequently release ROS in incised tissues via ST2-dependent mechanism. Transfer of excessive macrophages enhanced oxidative injury and reproduced mechanical allodynia in St2 -/- mice upon tissue incision. Overproduced ROS subsequently activated functionally up-regulated transient receptor potential ankyrin subtype-1 (TRPA1) channel innervating the incisional site to produce mechanical allodynia. Neither deleting St2 nor attenuating ROS affected wound healing of model mice.

Conclusions:

Our work uncovered a previously unrecognized contribution of IL-33/ST2 signaling in mediating mechanical allodynia and gait impairment of a mouse model of INC pain. Targeting IL-33/ST2 signaling could be a novel therapeutic approach for INC pain management.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Ratones Noqueados / Modelos Animales de Enfermedad / Interleucina-33 / Proteína 1 Similar al Receptor de Interleucina-1 / Canal Catiónico TRPA1 / Hiperalgesia / Macrófagos Límite: Animals Idioma: En Revista: Theranostics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Australia
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Ratones Noqueados / Modelos Animales de Enfermedad / Interleucina-33 / Proteína 1 Similar al Receptor de Interleucina-1 / Canal Catiónico TRPA1 / Hiperalgesia / Macrófagos Límite: Animals Idioma: En Revista: Theranostics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Australia