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Proteasome inhibitor MG132 modulates inflammatory pain by central mechanisms in adjuvant arthritis.
Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Family & Community Med, Huddinge, Sweden.
Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
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2017 (English)In: International journal of rheumatic diseases, ISSN 1756-185X, Vol. 20, no 1, 25-32 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: In rheumatoid arthritis (RA), pain and inflammation are initial symptoms followed by various degrees of bone and cartilage destruction. Previously, we have shown that reversible proteasome inhibitor MG132 attenuates pain and joint inflammation in a rat model of adjuvant-arthritis. Our present study aims to study the effects of MG132 on molecular changes in the dorsal root ganglia (DRG) and in the spinal cord (SC) using the same animal model.

METHODS: Arthritis was induced by heat-killed Mycobacterium butyricum in rats. The expression of substance P (SP) was analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in DRG and in the SC. The nuclear factor-κB (NF-κB) DNA-binding activity in the SC was analyzed by electromobility shift assay.

RESULTS: Arthritic rats treated daily with MG132 demonstrated a marked reduction of SP gene expression in the DRG and number of SP-positive cells was reduced. In the spinal cord of arthritic rats elevated SP messenger RNA levels were normalized and NF-κB-DNA-binding activity was down-regulated in arthritic rats treated with MG132.

CONCLUSION: Our results indicate that proteasome inhibitor MG132 attenuates pain in adjuvant arthritis by targeting the sensory neuropeptide substance P in the peripheral and central nervous systems. These effects may be mediated through the inhibition of NF-κB activation.

Place, publisher, year, edition, pages
2017. Vol. 20, no 1, 25-32 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-257445DOI: 10.1111/1756-185X.12353ISI: 000401871700002PubMedID: 24702728OAI: oai:DiVA.org:uu-257445DiVA: diva2:839332
Available from: 2015-07-02 Created: 2015-07-02 Last updated: 2017-06-14Bibliographically approved

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