Abstract
BackgroundThe exposure of the nucleus pulposus (NP) causes an immune and inflammatory response, which is intrinsically linked to the pathogenesis of radicular pain. As a newly discovered pro-resolving lipid mediator, maresin 1 (MaR1) could exert powerful inflammatory resolution, neuroprotection, and analgesic activities. In the present research, the analgesic effect of MaR1 was observed. Then, the potential mechanism by which MaR1 attenuated radicular pain was also analyzed in a rat model.MethodsIntrathecal administration of MaR1 (10 or 100 ng) was successively performed in a rat with non-compressive lumbar disk herniation for three postoperative days. Mechanical and thermal thresholds were determined to assess pain-related behavior from days 1 to 7 (n = 8/group). On day 7, the tissues of spinal dorsal horns from different groups were gathered to evaluate expression levels of inflammatory cytokines (IL-1β, IL-18, and TNF-α), the NLRP3 inflammasome and pyroptosis indicators (GSDMD, ASC, NLRP3, and Caspase-1), together with NF-κB/p65 activation (n = 6/group). TUNEL and PI staining were performed to further examine the process of pyroptosis.ResultsAfter intrathecal administration in the rat model, MaR1 exhibited potent analgesic effect dose-dependently. MaR1 significantly prompted the resolution of the increased inflammatory cytokine levels, reversed the up-regulated expression of the inflammasome and pyroptosis indicators, and reduced the cell death and the positive activation of NF-κB/p65 resulting from the NP application on the L5 dorsal root ganglion.ConclusionThis study indicated that the activation of NLRP3 inflammasome and pyroptosis played a significant role in the inflammatory reaction of radicular pain. Also, MaR1 could effectively down-regulate the inflammatory response and attenuate pain by inhibiting NLRP3 inflammasome-induced pyroptosis via NF-κB signaling.
Highlights
Radicular pain has become a public health concern with increasing prevalence and associated disability (Manchikanti and Hirsch, 2015), and lumbar disc herniation (LDH) is the most commonly identified contributor (Valat et al, 2010)
In order to investigate whether maresin 1 (MaR1) contributed to the alleviation of neuropathic pain, we first assessed the pain behavior in a rat model of non-compressive lumbar disc herniation (NCLDH)
The TUNEL staining measurement gave similar results (P < 0.001) (Figure 5B). These results revealed the presence of activation of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis in NCLDH models
Summary
Radicular pain has become a public health concern with increasing prevalence and associated disability (Manchikanti and Hirsch, 2015), and lumbar disc herniation (LDH) is the most commonly identified contributor (Valat et al, 2010). There is increasing recognition that neuroinflammation caused by exposure of the nucleus pulposus (NP) is intrinsically linked to the pathogenesis of radicular pain (Geiss et al, 2007; Park et al, 2011; Di Martino et al, 2013). Activated inflammasome triggers pyroptosis, a newly discovered proinflammatory programmed cell death, which cleaves cell membrane and induces extravasation of cellular contents, leading to inflammatory cascades (Shi et al, 2015). The exposure of the nucleus pulposus (NP) causes an immune and inflammatory response, which is intrinsically linked to the pathogenesis of radicular pain. As a newly discovered pro-resolving lipid mediator, maresin 1 (MaR1) could exert powerful inflammatory resolution, neuroprotection, and analgesic activities. The potential mechanism by which MaR1 attenuated radicular pain was analyzed in a rat model
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
