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Blocking brown adipocyte ß3-adrenoceptor attenuates blood-spinal cord barrier impairment and chronic postsurgical pain in a rat model of preoperative stress.
Zhu, Jixiang; Hou, Bailing; Rong, Hui; Xu, Ke; Jiang, Li; Yang, Shuai; Zhu, Huijie; Yang, Haikou; Jiao, Yang; Liu, Yue; Ni, Kun; Ma, Zhengliang.
Afiliación
  • Zhu J; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, China.
  • Hou B; Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
  • Rong H; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • Xu K; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • Jiang L; Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing Medical University, Nanjing 210008, China.
  • Yang S; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • Zhu H; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • Yang H; Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
  • Jiao Y; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • Liu Y; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: liuyueseu@163.com.
  • Ni K; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: lemonk_njumc@hotmail.com.
  • Ma Z; Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical
Int Immunopharmacol ; 128: 111530, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38278068
ABSTRACT
Preoperative stress has been recognized as an independent risk factor for chronic postsurgical pain (CPSP). However, the underlying mechanisms of CPSP influenced by preoperative stress remain elusive. Previous studies indicated that excessive stress could induce disruption of the blood-spinal cord barrier (BSCB). We wondered whether and how BSCB involves in CPSP by using a single prolonged stress (SPS) combining plantar incision model in male rats to mimic preoperative stress-related postsurgical pain. Here, we observed that preoperative SPS-exposed rats exhibited relentless incisional pain, which was accompanied by impairment of BSCB and persistent elevation of serum IL-6. Intraperitoneal injections of Tocilizumab (an IL-6 receptor monoclonal antibody) not only mitigated BSCB breakdown but also alleviated pain behaviors. In addition, intervening ß3-adrenoceptor (ADRB3) signaling in brown adipocytes by SR59230a (a specific ADRB3 antagonist) treatment or removal of brown adipose tissues could effectively decrease serum IL-6 levels, ameliorate BSCB disruption, and alleviate incisional pain. Further results displayed that SI-exposed rats also showed markedly spinal microglia activation. And exogenous His-tagged IL-6 could pass through the disrupted BSCB, which might contribute to microglia activation. Injection of SR59230a or ablation of brown adipose tissues could effectively reduce the activation of spinal microglia. Thus, our findings suggest that serum IL-6 induced by brown adipocyte ADRB3 signaling contributed to BSCB disruption and spinal microglia activation, which might be involved in preoperative stress mediated CPSP. This work indicates a promising treatment strategy for preoperative stress induced CPSP by blocking ADRB3.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Propanolaminas / Traumatismos de la Médula Espinal / Adipocitos Marrones Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Propanolaminas / Traumatismos de la Médula Espinal / Adipocitos Marrones Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos