ArticleJournal of neuroinflammation2013
Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.
Article in Journal of neuroinflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 113 citations in OpenAlex.
- Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Varying Analgesic Effectiveness of Systemic and Central Intrathecal Administration of Cyclooxygenase-2 Inhibitors in Different Phases of Osteoarthritic Pain in Rats.European journal of pain (London, England) · 2025Article
- Activation of TLR4/CCL2 in Intact Neurons Drives Radicular Injury-Induced Global Nerve Trunk Hypersensitivity in Radiculopathy Preclinical Models.Journal of pain research · 2025Article
- Myeloid Differentiation Primary Response Protein 88: An Important Therapeutic Target for Chronic Pain.Journal of pain research · 2025Review
- Late Bone Marrow Mononuclear Cell Transplantation in Rats with Sciatic Nerve Crush: Analysis of a Potential Therapeutic Time Window.International journal of molecular sciences · 2024Article
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.Molecular neurobiology · 2024Article
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Modulation of persistent bladder pain in mice: The role of macrophage migration inhibitory factor, high mobility group box-1, and downstream signaling pathways.Bladder (San Francisco, Calif.) · 2024Article
- Lipopolysaccharide-Induced TRPA1 Upregulation in Trigeminal Neurons is Dependent on TLR4 and Vesicular Exocytosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Toll-like receptors and their role in neuropathic pain and migraine.Molecular brain · 2022Review
- Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain.International journal of molecular sciences · 2022Review
- Intrathecal administration of the fat-mass and obesity-associated protein inhibitor mitigates neuropathic pain in female rats.Translational perioperative and pain medicine · 2022Article
- Sensory Neuron TLR4 mediates the development of nerve-injury induced mechanical hypersensitivity in female mice.Brain, behavior, and immunity · 2021Article
- Review
- Suppression of TLR4-MyD88 signaling pathway attenuated chronic mechanical pain in a rat model of endometriosis.Journal of neuroinflammation · 2021Article
- Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain.Brain, behavior, and immunity · 2021Article
- Cross-Talk of Toll-Like Receptor 5 and Mu-Opioid Receptor Attenuates Chronic Constriction Injury-Induced Mechanical Hyperalgesia through a Protein Kinase C Alpha-Dependent Signaling.International journal of molecular sciences · 2021Article
- Integrated traditional Chinese medicine alleviates sciatica while regulating gene expression in peripheral blood.Journal of orthopaedic surgery and research · 2021Article
- Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica.BMC neurology · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.
methodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.
resultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.
conclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice.
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