transforming-growth-factor-beta and Sciatica

Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment.. Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation.. RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes.. Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.

Topics: Animals; Coumaric Acids; Interleukin-10; Interleukin-4; Interleukin-6; Lipopolysaccharides; Myeloid Differentiation Factor 88; Neuroinflammatory Diseases; NF-kappa B; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sciatica; Signal Transduction; Toll-Like Receptor 4; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation.. Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, and transforming growth factor-β1 (TGF-β1) and the activation of nuclear factor-κB (NF-κB)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group).. The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-β1, and up-regulated the expression of TNF-α, IL-1β, NF-κB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF-α and IL-1β, increased the release of IL-10 and TGF-β1, and attenuated the expression of NF-κB/p65 and p-ERK in a dose-dependent manner.. The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-κB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Docosahexaenoic Acids; Extracellular Signal-Regulated MAP Kinases; Ganglia, Spinal; Hyperalgesia; Interleukin-10; Interleukin-1beta; Intervertebral Disc Displacement; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Sciatica; Spinal Cord Dorsal Horn; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha