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Lipopolysaccharide from Rhodobacter sphaeroides (TLR4 antagonist) attenuates hypersensitivity and modulates nociceptive factors.


ABSTRACT: CONTEXT:Accumulating evidence has demonstrated that Toll-like receptors (TLRs), especially TLR4 localized on microglia/macrophages, may play a significant role in nociception. OBJECTIVE:We examine the role of TLR4 in a neuropathic pain model. Using behavioural/biochemical methods, we examined the influence of TLR4 antagonist on levels of hypersensitivity and nociceptive factors whose contribution to neuropathy development has been confirmed. MATERIALS AND METHODS:Behavioural (von Frey's/cold plate) tests were performed with Wistar male rats after intrathecal administration of a TLR4 antagonist (LPS-RS ULTRAPURE (LPS-RSU), 20??G: lipopolysaccharide from Rhodobacter sphaeroides, InvivoGen, San Diego, CA) 16?H and 1?h before chronic constriction injury (cci) to the sciatic nerve and then daily for 7?d. three groups were used: an intact group and two cci-exposed groups that received vehicle or LPS-RSU. tissue [spinal cord/dorsal root ganglia (DRG)] for western blot analysis was collected on day 7. RESULTS:The pharmacological blockade of TLR4 diminished mechanical (from ca. 40% to 16% that in the INTACT group) and thermal (from ca. 51% to 32% that in the INTACT group) hypersensitivity despite the enhanced activation of IBA-1-positive cells in DRG. Moreover, LPS-RSU changed the ratio between IL-18/IL-18BP and MMP-9/TIMP-1 in favour of the increase of antinociceptive factors IL-18BP (25%-spinal; 96%-DRG) and TIMP-1 (15%-spinal; 50%-DRG) and additionally led to an increased IL-6 (40%-spinal; 161%-DRG), which is known to have analgesic properties in neuropathy. CONCLUSIONS:Our results provide evidence that LPS-RSU influences pain through the expression of TLR4. TLR4 blockade has analgesic properties and restores the balance between nociceptive factors, which indicates its engagement in neuropathy development.

SUBMITTER: Jurga AM 

PROVIDER: S-EPMC6130482 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Lipopolysaccharide from Rhodobacter sphaeroides (TLR4 antagonist) attenuates hypersensitivity and modulates nociceptive factors.

Jurga Agnieszka M AM   Rojewska Ewelina E   Makuch Wioletta W   Mika Joanna J  

Pharmaceutical biology 20181201 1


<h4>Context</h4>Accumulating evidence has demonstrated that Toll-like receptors (TLRs), especially TLR4 localized on microglia/macrophages, may play a significant role in nociception.<h4>Objective</h4>We examine the role of TLR4 in a neuropathic pain model. Using behavioural/biochemical methods, we examined the influence of TLR4 antagonist on levels of hypersensitivity and nociceptive factors whose contribution to neuropathy development has been confirmed.<h4>Materials and methods</h4>Behavioura  ...[more]

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