A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome
Autor: | Si-Cong Wang, Jun-Nan Wang, Qing-Xiang Zhao, Tao Sun, Yi-Hao Wang, Shuang Wen, Yan Li |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Docosahexaenoic Acids Inflammasomes Anti-Inflammatory Agents Endogeny Pharmacology Biochemistry Proinflammatory cytokine Pathogenesis Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Western blot NLR Family Pyrin Domain-Containing 3 Protein para-Aminobenzoates Medicine Animals Inflammation Analgesics Lumbar Vertebrae medicine.diagnostic_test business.industry Caspase 1 Inflammasome General Medicine Dipeptides Spinal cord medicine.disease Caspase Inhibitors 030104 developmental biology medicine.anatomical_structure Radicular pain Neuropathic pain Neuralgia business Low Back Pain 030217 neurology & neurosurgery Intervertebral Disc Displacement medicine.drug |
Zdroj: | Neurochemical research. 45(8) |
ISSN: | 1573-6903 |
Popis: | Inhibition of immune and inflammatory reaction induced by the expose of nucleus pulposus (NP) could effectively ameliorate neuropathic pain in the lumbar disc herniation. Maresin1 (MaR1), as a macrophage-derived mediator of inflammation resolution, displayed potent anti-inflammatory action. In the present study, we attempted to elucidate the impact of MaR1 on radicular pain and the interaction with NLRP3 inflammasome. We established a rat model of non-compressive lumbar disc herniation and different administration (MaR1 or Caspase-1 inhibitor) was given to them. The paw withdrawal latency (PWL) and paw withdrawal thresholds (PWTs) were observed to assess pain behaviors. The spinal cord horns were collected and the levels of IL-1β and IL-18 were measured by ELISA. The mRNA and protein expression levels of NLRP3 inflammasome components were tested by RT-PCR, western blot and immunohistochemistry. The endogenous MaR1 levels of the spinal cord were analyzed using LC-MS/MS. The application of NP in the models lead to mechanical and thermal hypersensitivity, increased IL-1β and IL-18 levels and expressions of NLRP3 inflammasome components, which were reversed markedly by administration of MaR1. Caspase-1 inhibition also improved mechanical hypersensitivity, decreased the expressions of inflammatory cytokines and restrained the activation of inflammasome. Meanwhile, Caspase-1 inhibitor promoted the endogenous MaR1 synthesis, which was hindered in the pain models. Altogether, our study indicated that the negative interaction between MaR1 and NLRP3 inflammasome mediated the inflammatory response in spinal dorsal horn, which involved in the pathogenesis of radicular pain. |
Databáze: | OpenAIRE |
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