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Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain.

ABSTRACT: Chronic pain arising from degenerative diseases of the joint such as osteoarthritis (OA) has a strong peripheral component which is likely to be mediator driven. Current treatments which reduce the production of such mediators i.e. non-steroidal anti-inflammatory drugs (NSAIDs), can help to lessen pain in OA patients. However, this is not always the case and complete pain relief is rarely achieved, suggesting that additional unidentified mediators play a role. Here we have investigated the notion that chemokines might act as such pain mediators in OA.Using the monosodium iodoacetate (MIA) model of chronic joint pain the expression of over 90 different inflammatory mediators, mainly cytokines and chemokines, were measured in tissues taken from the femorotibial joint (cartilage, subchondral bone, fat pad) using custom-made quantitative real-time polymerase chain reaction (qPCR) array cards. At both the day 3 and 14 time points, numerous inflammatory mediators were significantly up-regulated in these tissues, although it was clear that the largest transcriptional dysregulation occurred in the cartilage. Using individual qPCR to measure immune cell markers, a significant infiltration of macrophages was measured in the cartilage and fat pad at day 3. Neutrophil infiltration was also measured in the fat pad at the same time point, but no infiltration was observed at day 14. Combination of mRNA expression data from different time points and tissues identified the chemokines, CCL2, 7 and 9 as being consistently up-regulated. The overall increase in CCL2 expression was also measured at the protein level.Chemokines in general and CCL2, 7 and 9 in particular, represent promising targets for further studies into the identification of new pain mediators in chronic joint pain.

SUBMITTER: Dawes JM

PROVIDER: S-EPMC3835139 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

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Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain.

Dawes John M JM Kiesewetter Hannes H Perkins James R JR Bennett David L H DL McMahon Stephen B SB

Molecular pain 20131108

<h4>Background</h4>Chronic pain arising from degenerative diseases of the joint such as osteoarthritis (OA) has a strong peripheral component which is likely to be mediator driven. Current treatments which reduce the production of such mediators i.e. non-steroidal anti-inflammatory drugs (NSAIDs), can help to lessen pain in OA patients. However, this is not always the case and complete pain relief is rarely achieved, suggesting that additional unidentified mediators play a role. Here we have inv ...[more]

PMID: 24206615

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Project description:BackgroundClinical studies of osteoarthritis (OA) suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA) model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia) was assessed. Spinal cord microglia (Iba1 staining) and astrocyte (GFAP immunofluorescence) activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed.ResultsSeven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p < 0.05, compared to contralateral levels and compared to saline controls). Levels of activated microglia were significantly elevated at day 14 and 21 post MIA-injection. At day 28, microglia activation was significantly correlated with distal allodynia (p < 0.05). Ipsilateral spinal GFAP immunofluorescence was significantly (p < 0.01) increased at day 28, but not at earlier timepoints, in the MIA model, compared to saline controls. Repeated oral dosing (days 14-20) with nimesulide attenuated pain behaviour and the activation of microglia in the ipsilateral spinal cord at day 21. This dosing regimen also significantly attenuated distal allodynia (p < 0.001) and numbers of activated microglia (p < 0.05) and GFAP immunofluorescence (p < 0.001) one week later in MIA-treated rats, compared to vehicle-treated rats. Repeated administration of minocycline also significantly attenuated pain behaviour and reduced the number of activated microglia and decreased GFAP immunofluorescence in ipsilateral spinal cord of MIA treated rats.ConclusionsHere we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

Project description:STUDY DESIGN: Systematic reviewObjective: To compare the safety and effectiveness of fusion versus denervation for chronic sacroiliac joint pain after failed conservative management. SUMMARY OF BACKGROUND: METHODS of confirming the sacroiliac joint as a pain source have been extensively studied and reported in the literature. After confirmation of the origin of the pain by positive local anesthetic blocks, chronic sacroiliac joint pain is usually managed with a combination of medication, physical therapies, and injections. We have chosen to compare two alternative treatments for sacroiliac pain that was refractory to conservative therapies. METHODS: A systematic review of the English-language literature was undertaken for articles published between 1970 and June 2010. Electronic databases and reference lists of key articles were searched to identify studies evaluating fusion or denervation for chronic sacroiliac joint pain after failed conservative management. Studies involving only conservative treatment or traumatic onset of injury were excluded. Two independent reviewers assessed the level of evidence quality using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. RESULTS: We identified eleven articles (six fusion, five denervation) meeting our inclusion criteria. The majority of patients report satisfaction after both treatments. Both treatments reported mean improvements in pain and functional outcome. Rates of complications were higher among fusion studies (13.7%) compared to denervation studies (7.3%). Only fusion studies reported infections (5.3%). No infections were reported among denervation patients. The evidence for all findings were very low to low; therefore, the relative efficacy or safety of one treatment over another cannot be established. CONCLUSIONS: Sacroiliac joint fusion or denervation can reduce pain for many patients. Whether a true arthrodesis of the joint is achieved by percutaneous techniques is open to question and whether denervation of the joint gives durable pain relief is not clear. Further comparative studies of these two techniques may provide the answers.

Dataset Information

Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain.

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Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain.

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