ArticlePain2013
Spinal toll-like receptor signaling and nociceptive processing: regulatory balance between TIRAP and TRIF cascades mediated by TNF and IFNβ.
Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Precuneus hyperexcitability mediates inflammatory-driven pain hypersensitivity following sleep disruption: a multimodal neuroimaging study.Frontiers in immunology · 2026Article
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- Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis.Arthritis research & therapy · 2024Article
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
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- Emerging Roles of Type-I Interferons in Neuroinflammation, Neurological Diseases, and Long-Haul COVID.International journal of molecular sciences · 2022Review
- Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.Cold Spring Harbor perspectives in medicine · 2021Review
- Interferons in Pain and Infections: Emerging Roles in Neuro-Immune and Neuro-Glial Interactions.Frontiers in immunology · 2021Review
- Lipid rafts in glial cells: role in neuroinflammation and pain processing.Journal of lipid research · 2020Review
- Regulation of lipid rafts, angiogenesis and inflammation by AIBP.Current opinion in lipidology · 2019Review
- Targeting toll-like receptor-4 (TLR4)-an emerging therapeutic target for persistent pain states.Pain · 2018Review
- Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States.Cell reports · 2018Article
- Toll-like receptors and their role in persistent pain.Pharmacology & therapeutics · 2018Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) play a pivotal role in inflammatory processes, and individual TLRs have been investigated in nociception. We examined overlapping and diverging roles of spinal TLRs and their associated adaptor proteins in nociceptive processing. Intrathecal (IT) TLR2, TLR3, or TLR4 ligands (-L) evoked persistent (7-day) tactile allodynia (TA) that was abolished in respective TLR-deficient mice. Using Tnf(-/-) mice, we found that IT TLR2 and TLR4 TA was tumor necrosis factor (TNF) dependent, whereas TLR3 was TNF-independent. In Toll-interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP; Tirap(-/-)) mice (downstream to TLR2 and TLR4), allodynia after IT TLR2-L and TLR4-L was abolished. Unexpectedly, in TIR-domain-containing adapter-inducing interferon-β (Trif(lps2)) mice (downstream of TLR3 and TLR4), TLR3-L allodynia was abrogated, but intrathecal TLR4-L produced a persistent increase (>21days) in TA. Consistent with a role for interferon (IFN) β (downstream to TIR-domain-containing adapter-inducing IFNβ [TRIF]) in regulating recovery after IT TLR4-L, prolonged allodynia was noted in Ifnar1(-/-) mice. Further, IT IFNβ given to Trif(lps2) mice reduced TLR4 allodynia. Hence, spinal TIR domain-containing adaptor protein (TIRAP) and TRIF cascades differentially lead to robust TA by TNF-dependent and independent pathways, whereas activation of TRIF modulated processing through type I IFN receptors. Based on these results, we believe that processes leading to the activation of these spinal TLRs initiate TNF-dependent and -independent cascades, which contribute to the associated persistent pain state. In addition, TRIF pathways are able to modulate the TNF-dependent pain state through IFNβ.
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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.