ArticleMolecular pain
TLR4/NF-κB signaling activation in plantar tissue and dorsal root ganglion involves in the development of postoperative pain.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Focusing on inflammation-driven pyroptosis in postherpetic neuralgia: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury.Communications biology · 2025Article
- Endogenous inflammatory mediators produced by injury activate TRPV1 and TRPA1 nociceptors to induce sexually dimorphic cold pain that is dependent on TRPM8 and GFRα3.bioRxiv : the preprint server for biology · 2023Article
- Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.Neural plasticity · 2023Article
- Sciatic Nerve Block Combined with Flurbiprofen Inhibits Spinal Cord Inflammation and Improves Postoperative Pain in Rats with Plantar Incision.Journal of pain research · 2023Article
- TLR4 activation by lysozyme induces pain without inflammation.Frontiers in immunology · 2023Article
- Article
- Activation of Double-Stranded RNA-Activated Protein Kinase in the Dorsal Root Ganglia and Spinal Dorsal Horn Regulates Neuropathic Pain Following Peripheral Nerve Injury in Rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- The different mechanisms of peripheral and central TLR4 on chronic postsurgical pain in rats.Journal of anatomy · 2021Article
- Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain.Brain, behavior, and immunity · 2021Article
- Toll-like receptor 4/nuclear factor-kappa B pathway is involved in radicular pain by encouraging spinal microglia activation and inflammatory response in a rat model of lumbar disc herniation.The Korean journal of pain · 2021Article
- Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes.Annals of translational medicine · 2020Article
- Toll-like Receptor 4 Signaling in Neurons Enhances Calcium-Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Currents and Drives Post-Traumatic Epileptogenesis.Annals of neurology · 2020Article
- Chronic morphine-mediated upregulation of high mobility group box 1 in the spinal cord contributes to analgesic tolerance and hyperalgesia in rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Knockdown of miR-222 inhibits inflammation and the apoptosis of LPS-stimulated human intervertebral disc nucleus pulposus cells.International journal of molecular medicine · 2019Article
- A Novel Sex-Dependent Target for the Treatment of Postoperative Pain: The NLRP3 Inflammasome.Frontiers in neurology · 2019Review
- MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1.Neural plasticity · 2019Article
- microRNA-181a contributes to gastric hypersensitivity in rats with diabetes by regulating TLR4 expression.Molecular painArticle
- Mechanism of Incisional Pain: Novel Finding on Long Noncoding RNA XIST/miR-340-5p/RAB1A Axis.ASN neuroArticle
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Severe postoperative pain remains a clinical problem that impacts patient's rehabilitation. The present work aims to investigate the role of Toll-like receptor-4 (TLR4) activation in wounded plantar tissue and dorsal root ganglion (DRG) in the genesis of postoperative pain and its underlying mechanisms. Results Postoperative pain was induced by plantar incision in rat hind paw. Plantar incision led to increased expression of TLR4 in ipsilateral lumbar 4-5 (L4/L5) DRGs, which occurred at 2 h and was persistent to the third day after surgery. Similar to the change in TLR4 expression, there was also significant increase in phosphorylated nuclear factor-kappa B p65 (p-p65) in DRGs after surgery. Immunofluorescence staining revealed that the increased expressions of TLR4 and p-p65 not only in neuronal cells but also in satellite glial cells in DRG. Furthermore, the enhanced expressions of TLR4 and p-p65 were also detected in plantar tissues around the incision, which was observed starting at 2 h and lasting until the third day after surgery. Prior intrathecal (i.t.) injections of TAK-242 (a TLR4-specific antagonist) or 4',6-diamidino-2-phenylindole-dihydrochloride (PDTC, a nuclear factor-kappa B activation inhibitor) dose dependently alleviated plantar incision-induced mechanical allodynia and thermal hyperalgesia and inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta in DRG. Prior subcutaneous (s.c.) plantar injection of TAK-242 or PDTC also ameliorated pain-related hypersensitivity following plantar incision. Moreover, the plantar s.c. injection of TAK-242 or PDTC inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta not only in local wounded plantar tissue but also dramatically in ipsilateral lumbar 4-5 DRGs. Conclusion TLR4/ nuclear factor-kappa B signaling activation in local injured tissue and DRG contribute to the development of postoperative pain via regulating pro-inflammatory cytokines release. Targeting TLR4/ nuclear factor-kappa B signaling in local tissue at early stage of surgery may be an effective strategy for the treatment of postoperative pain.
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