Spinal Toll-like receptor signaling and nociceptive processing: Regulatory balance between TIRAP and TRIF cascades mediated by TNF and IFNβ

Stokes, Jennifer; Corr, Maripat; Yaksh, Tony L.

doi:10.1016/j.pain.2013.01.012

Cited by 42 publications

(46 citation statements)

References 60 publications

(102 reference statements)

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“…The i.t. saline/saline group was similar to the naive group but the greater spread likely reflects some degree of activation of TLR4 signaling secondary to the intrathecal needle placement (Stokes et al, 2013b). …”

Section: Resultsmentioning

confidence: 96%

“…AIBP on the expression of several pain states known to be associated with neuraxial TLR4 signaling. Tlr4 gene knockout or mutant mice are fully protected from tactile allodynia in the models of facilitated pain tested below (Cao et al, 2009; Park et al, 2014; Saito et al, 2010; Sorge et al, 2011; Stokes et al, 2013a; Stokes et al, 2013b; Woller et al, 2015). Accordingly, we addressed the effects of i.t.…”

Section: Resultsmentioning

confidence: 99%

“…To address the functional impact of AIBP on TLR4 signaling, we took note of the evolving understanding of the role played by neuraxial TLR4 in regulating the development of facilitated pain states generated by tissue and nerve injury (Park et al, 2014; Saito et al, 2010; Sorge et al, 2011; Stokes et al, 2013b; Woller et al, 2015). TLR4 deficiency in mice prevents the tactile allodynia otherwise evolving over time after afferent activation, as observed with intraplantar formalin (Woller et al, 2016) or as seen with the chemotherapeutic agent cisplatin (Park et al, 2014; Woller et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Tellingly, intrathecal (i.t.) injection of LPS, a specific TLR4 ligand, but not of LPS-RS, which does not activate TLR4, results in immediate tactile allodynia (Stokes et al, 2013b). The underlying mechanism involves TLR4-mediated release of inflammatory cytokines from microglia and/or astrocytes, which in turn leads to central sensitization and allodynia (Inoue and Tsuda, 2018; Miller et al, 2015; Stokes et al, 2013b; Sun et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…injection of LPS, a specific TLR4 ligand, but not of LPS-RS, which does not activate TLR4, results in immediate tactile allodynia (Stokes et al, 2013b). The underlying mechanism involves TLR4-mediated release of inflammatory cytokines from microglia and/or astrocytes, which in turn leads to central sensitization and allodynia (Inoue and Tsuda, 2018; Miller et al, 2015; Stokes et al, 2013b; Sun et al, 2015). We thus believe that the development of neuropathic pain depends at least in part on the release of endogenous TLR4 agonists, such as HMGB1 and HSP70 (Agalave et al, 2014; Feldman et al, 2012; Hutchinson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States

et al. 2018

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SUMMARY Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting removal of excess of cholesterol from the plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves AIBP binding to Toll-like-receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulated LPS-induced TLR4 dimerization, inflammatory signaling and expression of cytokines in microglia. In mice, intrathecal injections of AIBP reduced spinal myeloid cell lipid rafts, TLR4 dimerization, neuroinflammation, and glial activation. Intrathecal AIBP reversed established allodynia in mice in which pain states were induced by the chemotherapeutic cisplatin, intraplantar formalin, or intrathecal LPS, all pro-nociceptive interventions known to be regulated by TLR4 signaling. These findings demonstrate a mechanism by which AIBP regulates neuroinflammation and suggest the therapeutic potential for AIBP in treating preexisting pain states.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States

et al. 2018

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Schwann cells as a target cell for the treatment of cancer pain

Zhang

Liu

2023

Glia

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Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen the suffering of patients with cancer. Reception and transmission of sensory signal receptors, abnormal activation of primary sensory neurons, and activation of glial cells are involved in cancer pain. Therefore, exploring promising therapeutic methods to suppress cancer pain is of great significance. Various studies have found that the use of functionally active cells is a potentially effective way to relieve pain. Schwann cells (SCs) act as small, biologically active pumps that secrete pain-relieving neuroactive substances. Moreover, SCs can regulate the progression of tumor cells, including proliferation and metastasis, through neuro-tumor crosstalk, which emphasizes the critical role of SCs in cancer and cancer pain. The mechanisms by which SCs repair injured nerves and exert analgesia include neuroprotection, neurotrophy, nerve regeneration, neuromodulation, immunomodulation, and enhancement of the nerve-injury microenvironment. These factors may ultimately restore the damaged or stimulated nerves and contribute to pain relief. Strategies for pain treatment using cell transplantation mainly focus on analgesia and nerve repair. Although these cells are in the initial stages of nerve repair and pain, they open new avenues for the treatment of cancer pain. Therefore, this paper discusses, for the first time, the possible mechanism of SCs and cancer pain, and new strategies and potential problems in cancer pain treatment.

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Perspectives on pain in Down syndrome

Shaikh

2023

Medicinal Research Reviews

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Down syndrome (DS) or trisomy 21 is a genetic condition often accompanied by chronic pain caused by congenital abnormalities and/or conditions, such as osteoarthritis, recurrent infections, and leukemia. Although DS patients are more susceptible to chronic pain as compared to the general population, the pain experience in these individuals may vary, attributed to the heterogenous structural and functional differences in the central nervous system, which might result in abnormal pain sensory information transduction, transmission, modulation, and perception. We tried to elaborate on some key questions and possible explanations in this review. Further clarification of the mechanisms underlying such abnormal conditions induced by the structural and functional differences is needed to help pain management in DS patients.

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Spinal Toll-like receptor signaling and nociceptive processing: Regulatory balance between TIRAP and TRIF cascades mediated by TNF and IFNβ

Cited by 42 publications

References 60 publications

Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States

Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States

Schwann cells as a target cell for the treatment of cancer pain

Perspectives on pain in Down syndrome

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