Challenging the challenge: A randomized controlled trial evaluating the inflammatory response and pain perception of healthy volunteers after single-dose LPS administration, as a potential model for inflammatory pain in early-phase drug development

Hijma, H.J.; Moss, Laurence; Gal, Pim; Ziagkos, Dimitrios; Kam, Marieke L. de; Moerland, Matthijs; Groeneveld, Geert Jan

doi:10.1016/j.bbi.2020.04.033

Cited by 13 publications

(24 citation statements)

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“…The formalin model mainly represents the spontaneous pain behavior and hypersensitivity of mechanical and thermal stimulation [ 20 ]. LPS, as a major factor of gram-negative bacteria, binds to Toll receptors and triggers an intracellular signal cascade and subsequently produces inflammatory cytokines, causing neutrophil and macrophage recruitment [ 14 , 21 ]. In this study, we used two different animal models.…”

Section: Discussionmentioning

confidence: 99%

CY-09 Inhibits NLRP3 Inflammasome Activation to Relieve Pain via TRPA1

Fan

Xue

Chen

et al. 2021

Computational and Mathematical Methods in Medicine

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Peripheral tissue damage leads to inflammatory pain, and inflammatory cytokine releasing is the key factor for inducing the sensitization of nociceptors. As a calcium ion channel, TRPA1 plays an important role in pain and inflammation, thus becoming a new type of anti-inflammatory and analgesic target. However, there is no consensus on the role of this channel in mechanical hyperalgesia caused by inflammation. Here, we aim to explore the role and underlying mechanism of the inflammasome inhibitor CY-09 in two classic inflammatory pain models. We evaluated pain behavior on animal models, cytokine levels, intracellular Ca2+ levels, transient TRPA1 expression, NF-κB transcription, and NLPR3 inflammasome activation. Consistently, CY-09 reduced the production of inflammatory cytokines, intracellular Ca2+ levels, and the activation of TRPA1 by inhibiting the activation of inflammasomes, thereby reducing the proinflammatory polarization of macrophages and alleviating animal pain and injury. Importantly, AITC (TRPA1 agonist) significantly reversed the analgesic effect of CY-09, indicating that TRPA1 was involved in the analgesic effect of CY-09. Our findings indicate that CY-09 relieves inflammation and pain via inhibiting TRPA1-mediated activation of NLRP3 inflammasomes. Thus, NLRP3 inflammasome may be a potential therapeutic target for pain treatment and CY-09 may be a pharmacological agent to relieve inflammatory pain, which needs further research.

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Section: Discussionmentioning

confidence: 99%

CY-09 Inhibits NLRP3 Inflammasome Activation to Relieve Pain via TRPA1

Fan

Xue

Chen

et al. 2021

Computational and Mathematical Methods in Medicine

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“…This is a sub-study of a larger previously published study [ 4 ]. This sub-study included ten healthy male volunteers who received a single dose of 1 or 2 ng/kg bodyweight of LPS.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were collected pre-LPS exposure up to 24 h post LPS administration. Further study details can be found in the primary publication [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

et al. 2022

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“…In this way these bacterial components, once recognised by the host immune system, have an indirect impact on pain manifestation but other factors may contribute to the degree of pain. LPS for example has been established as playing a role in inflammatory pain ( Hijma et al, 2020 ). We have previously shown that a genetic predisposition to stress compromised the coordinated CNS response to this peripheral immune activation with a blunted pain response ( O'Mahony et al, 2013 ).…”

Section: Indirect Interactions Between Microbes and The Nervous System In Painmentioning

confidence: 99%