S Ashraf1, P I Mapp2, S M Shahtaheri3, D A Walsh4. 1. School of Pharmacy, University of Nottingham, Nottingham, UK; Arthritis Research UK Pain Centre and NIHR Nottingham BRC, University of Nottingham, Nottingham, UK. Electronic address: sadaf.ashraf@nottingham.ac.uk. 2. Arthritis Research UK Pain Centre and NIHR Nottingham BRC, University of Nottingham, Nottingham, UK. Electronic address: paul.mapp@hotmail.com. 3. Arthritis Research UK Pain Centre and NIHR Nottingham BRC, University of Nottingham, Nottingham, UK. Electronic address: mszsms2@exmail.nottingham.ac.uk. 4. Arthritis Research UK Pain Centre and NIHR Nottingham BRC, University of Nottingham, Nottingham, UK. Electronic address: david.wlash@nottingham.ac.uk.
Abstract
OBJECTIVE: Knee osteoarthritis (OA) is associated with ongoing pain and joint damage that can be punctuated by acute flares of pain and inflammation. Synovitis in normal knees might resolve without long-term detriment to joint function. We hypothesised that osteoarthritis is associated with impaired resilience to inflammatory flares. DESIGN: We induced synovitis by injecting carrageenan into rat knees with or without meniscal transection (MNX)-induced OA, and measured synovitis, weightbearing asymmetry (pain behaviour), and joint damage up to 35 days after OA induction (23 days after carrageenan-injection). RESULTS: Carrageenan injection induced weightbearing asymmetry for 1 week, transient increase in knee diameter for 2 days, and a sustained increase in synovial macrophages, endothelial cell proliferation and vascular density compared with naive vehicle-injected controls. MNX surgery induced weightbearing asymmetry and histological evidence of OA. Carrageenan-injection in MNX-operated knees was followed for 2 days by increased weightbearing asymmetry compared either to MNX+vehicle or to sham+carrageenan groups. OA structural damage and synovitis at day 35 were greater in MNX+carrageenan compared to MNX+vehicle and sham+carrageenan groups. Carrageenan injection did not induce OA in Sham-operated knees. CONCLUSION: Intra-articular injection of the pro-inflammatory compound carrageenan in OA and sham-operated control knees induced a short term increase in joint pain. Even though pain flares resolved in both groups and damage was not induced in sham-operated knees, carrageen injection exacerbated long-term joint damage in OA knees. OA knees display less resilience to inflammatory episodes. Preventing inflammatory flares may be particularly important in preventing symptoms and long term joint damage in OA.
OBJECTIVE:Knee osteoarthritis (OA) is associated with ongoing pain and joint damage that can be punctuated by acute flares of pain and inflammation. Synovitis in normal knees might resolve without long-term detriment to joint function. We hypothesised that osteoarthritis is associated with impaired resilience to inflammatory flares. DESIGN: We induced synovitis by injecting carrageenan into rat knees with or without meniscal transection (MNX)-induced OA, and measured synovitis, weightbearing asymmetry (pain behaviour), and joint damage up to 35 days after OA induction (23 days after carrageenan-injection). RESULTS:Carrageenan injection induced weightbearing asymmetry for 1 week, transient increase in knee diameter for 2 days, and a sustained increase in synovial macrophages, endothelial cell proliferation and vascular density compared with naive vehicle-injected controls. MNX surgery induced weightbearing asymmetry and histological evidence of OA. Carrageenan-injection in MNX-operated knees was followed for 2 days by increased weightbearing asymmetry compared either to MNX+vehicle or to sham+carrageenan groups. OA structural damage and synovitis at day 35 were greater in MNX+carrageenan compared to MNX+vehicle and sham+carrageenan groups. Carrageenan injection did not induce OA in Sham-operated knees. CONCLUSION: Intra-articular injection of the pro-inflammatory compound carrageenan in OA and sham-operated control knees induced a short term increase in joint pain. Even though pain flares resolved in both groups and damage was not induced in sham-operated knees, carrageen injection exacerbated long-term joint damage in OA knees. OA knees display less resilience to inflammatory episodes. Preventing inflammatory flares may be particularly important in preventing symptoms and long term joint damage in OA.
Authors: Sadaf Ashraf; Masar Radhi; Peter Gowler; James J Burston; Raj D Gandhi; Graeme J Thorn; Anna M Piccinini; David A Walsh; Victoria Chapman; Cornelia H de Moor Journal: Sci Rep Date: 2019-03-18 Impact factor: 4.379
Authors: Arjen B Blom; Martijn H van den Bosch; Esmeralda N Blaney Davidson; Johannes Roth; Thomas Vogl; Fons A van de Loo; Marije Koenders; Peter M van der Kraan; Edwin J Geven; Peter L van Lent Journal: Arthritis Res Ther Date: 2020-08-27 Impact factor: 5.156