Dataset Information

Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

ABSTRACT: Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs). However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs) as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP) genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18?1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18?1, 9-and 13-HODE and HETEs.

SUBMITTER: Sisignano M

PROVIDER: S-EPMC3857181 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

Sisignano Marco M Angioni Carlo C Ferreiros Nerea N Schuh Claus-Dieter CD Suo Jing J Schreiber Yannick Y Dawes John M JM Antunes-Martins Ana A Bennett David L H DL McMahon Stephen B SB Geisslinger Gerd G Scholich Klaus K

PloS one 20131209 12

Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs). However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inf ...[more]

PMID: 24349046

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Project description:BackgroundInflammation often leads to the occurrence of chronic pain, and many miRNAs have been shown to play a key role in the development of inflammatory pain. However, whether miR-26a-5p relieves pain induced by inflammation and its possible mechanism are still unclear.MethodsThe complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model was employed. Intrathecal or subcutaneous injection of miR-26a-5p agomir was performed after modeling to study its antinociceptive effect and the comparison of different administration methods. Bioinformatics analysis of miRNAs was performed to study the downstream mechanisms of miR-26a-5p. HE staining, RT-qPCR, Western blotting, and immunofluorescence were used for further validation.ResultsA single intrathecal and subcutaneous injection of miR-26a-5p both reversed mechanical hypersensitivity and thermal latency in the left hind paw of mice with CFA-induced inflammatory pain. HE staining and immunofluorescence studies found that both administrations of miR-26a-5p alleviated inflammation in the periphery and spinal cord. Bioinformatics analysis and dual-luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR-26a-5p. Wnt5a was mainly expressed in neurons and microglia in the spinal cord of mice with inflammatory pain. Intrathecal injection of miR-26a-5p could significantly reduce the expression level of Wnt5a and inhibit the downstream molecules of noncanonical Wnt signaling Camk2/NFAT, inhibiting the release of spinal cord inflammatory factors and alleviating the activation of microglia. In addition, miR-26a-5p could also inhibit lipopolysaccharide (LPS)-stimulated BV2 cell inflammation in vitro through a noncanonical Wnt signaling pathway.ConclusionsmiR-26a-5p is a promising therapy for CFA-induced inflammatory pain. Both intrathecal and subcutaneous injections provide relief for inflammatory pain. miR-26a-5p regulated noncanonical Wnt signaling to be involved in analgesia partly through antineuroinflammation, suggesting a pain-alleviating effect via noncanonical Wnt signaling pathway in the CFA-induced inflammatory pain model in vivo.

Project description:The aim of this study was to investigate the inhibitory effect of salvianolic acid on inflammatory mediators of rats with collagen-induced rheumatoid arthritis (RA). Thirty rats were randomly divided into the normal control group, collagen-induced arthritis model group (CIA model group) and drug group (Salvianolic Acid-CIA group). In the model group, the CIA models were established through intradermal injection of collagen emulsion at the toes. At 3 weeks after the model establishment, grouped drug administration was conducted, of which salvianolic acid was given by gavage to Salvianolic Acid-CIA group. The degrees of joint swelling of each group of rats were recorded. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of relevant inflammatory mediators, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the messenger RNA (mRNA) expression levels of serum necrosis factor-alpha (TNF-?), interleukin-6 (IL-6) and prostaglandin E2 (PGE2), and hematoxylin and eosin staining was utilized to detect the pathological characteristics of the synovial tissues. After the establishment of models, the ankle joint swelling degree of rats in the model group was more obvious compared with that in the normal control group (P<0.01). After 3 weeks of drug administration, the ankle joint swelling degree of rats in the Salvianolic Acid-CIA group was alleviated compared with that in the model group (P<0.05). The contents of TNF-?, IL-6 and PGE2 in Salvianolic Acid-CIA group were obviously lower than those in the model group (P<0.01). The mRNA expression levels of TNF-?, IL-6 and PGE2 in the Salvianolic Acid-CIA group were markedly lower than those in the model group. The hyperemia of rat synovial tissues in Salvianolic Acid-CIA group was obviously relieved compared with that in the CIA model group. In conclusion, the models of CIA rats are successfully established, and the results show salvianolic acid has an inhibitory effect on the RA of CIA model rats and can significantly inhibit the expression levels of relevant inflammatory mediators.

Dataset Information

Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

Publications

Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

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