A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome

• Published in: Neurochemical research Vol. 45; no. 8; pp. 1860 - 1869
• Main Authors: Wang, Yi-hao, Li, Yan, Wang, Jun-nan, Zhao, Qing-xiang, Wen, Shuang, Wang, Si-cong, Sun, Tao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2020; Springer Nature B.V
• Subjects: Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedicine; Caspase 1 - metabolism; Caspase Inhibitors - pharmacology; Caspase-1; Cell Biology; Cytokines; Dipeptides - pharmacology; Docosahexaenoic Acids - therapeutic use; Dorsal horn; Enzyme-linked immunosorbent assay; Gene expression; Hypersensitivity; IL-1β; Immunohistochemistry; Inflammasomes; Inflammasomes - antagonists & inhibitors; Inflammation; Inflammation - drug therapy; Inflammation - epidemiology; Inflammatory response; Inhibitors; Interleukin 18; Intervertebral Disc Displacement - complications; Intervertebral discs; Latency; Lipids; Low Back Pain - drug therapy; Low Back Pain - epidemiology; Lumbar Vertebrae - drug effects; Macrophages; Male; mRNA; Neuralgia; Neuralgia - drug therapy; Neuralgia - epidemiology; Neurochemistry; Neurology; Neurosciences; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nucleus pulposus; Original Paper; Pain; para-Aminobenzoates - pharmacology; Pathogenesis; Polymerase chain reaction; Rats, Sprague-Dawley; Spinal cord; Maresin 1 (MaR1); NLRP3 inflammasome; Radicular pain; Endogenous biosynthesis; Caspase-1 inhibitor
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-020-03050-x

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.