ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
263 citing papers in PubMed, 1 synthesis or guideline pooled it, 464 citations in OpenAlex.
- Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.Pain · 2019Pooled it
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Sex-Specific Mechanisms of Central Sensitization: A Narrative Review of the Neuroimmune Architecture of Chronic Pain.Cureus · 2026Review
- Incision-triggered neuroimmune remodeling of nociceptor ion channels: from postoperative inflammation to pain chronification.Frontiers in immunology · 2026Review
- Spinal Mincle activation as a new model of neuroinflammation-associated neuropathic pain: comparison with spinal nerve ligation.The Korean journal of pain · 2026Article
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
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- TLR4 deletion reduces small fiber sensory abnormalities and nerve degeneration in diabetic male mice.Neuroscience · 2025Article
- The Small Molecule Compound Eupalinolide B Alleviates Neuropathic Pain by Regulating the USP7/Keap1/Nrf2 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
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- A pathological missense mutation in the deubiquitinase USP5 leads to insensitivity to pain.The Journal of experimental medicine · 2025Article
- Hyperalgesia in the Psychological Stress-Induced Fibromyalgia Model Shows Sexual Dimorphism Mediated by LPACells · 2025Article
- Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain.Nature communications · 2025Article
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- A neural circuit for sex-dependent conditioned pain hypersensitivity in mice.Nature communications · 2025Article
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- Multi-omic integration with human DRG proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway.bioRxiv : the preprint server for biology · 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
203 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The innate immune system is increasingly appreciated to play an important role in the mediation of chronic pain, and one molecule implicated in this process is the Toll-like receptor 4 (TLR4). Here, using pharmacological and genetic manipulations, we found that activating TLR4 in the spinal cord, with the agonist lipopolysaccharide (LPS), causes robust mechanical allodynia but only in male mice. Spinal LPS had no pain-producing effect in female mice. TLR4 also has a sex-specific role in inflammatory (complete Freund's adjuvant) and neuropathic (spared nerve injury) pain: pain behaviors were TLR4 dependent in males but TLR4 independent in females. The sex differences appear to be specific to the spinal cord, as LPS administered to the brain or the hindpaw produces equivalent allodynia in both sexes, and specific to pain, as intrathecal LPS produces equivalent hypothermia in both sexes. The involvement of TLR4 in pain behaviors in male mice is dependent on testosterone, as shown by gonadectomy and hormone replacement. We found no sex differences in spinal Tlr4 gene expression at baseline or after LPS, suggesting the existence of parallel spinal pain-processing circuitry in female mice not involving TLR4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.