Proteasome inhibitor MG132 modulates inflammatory pain by central mechanisms in adjuvant arthritis. (5th April 2014)

• Record Type: Journal Article
• Authors: Ahmed, Aisha Siddiqah; Ahmed, Mahmood; Li, Jian; Gu, Harvest F.; Bakalkin, Georgy; Stark, André; Harris, Helena Erlandsson
• Is Part Of: International journal of rheumatic diseases. Volume 20:Number 1(2017)
• Page Start: 25
• Page End: 32
• Publication Date: 2014-04-05
• Subjects: pain -- rheumatoid arthritis -- spinal cord -- substance P -- ubiquitin proteasome system; Rheumatology -- Periodicals; Rheumatology -- Asia -- Periodicals; Rheumatology -- Pacific Area -- Periodicals; Rheumatic Diseases -- Periodicals; Connective Tissue Diseases -- Periodicals; Immune System Diseases -- Periodicals; 616.723
• DOI: 10.1111/1756-185X.12353
• Languages: English
• ISSNs: 1756-1841

Abstract

Abstract: 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.