Abstract:
INTRODUCTION:During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful. Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common. Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation. One enzyme responsible for endocannabinoid breakdown is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis. METHODS:Acute joint inflammation was induced in male C57BL/6 mice by intra-articular injection of 2% kaolin/2% carrageenan. After 24 hr, articular leukocyte kinetics and blood flow were used as measures of inflammation, while hindlimb weight bearing and von Frey hair algesiometry were used as measures of joint pain. The effects of local URB597 administration were then determined in the presence or absence of either the cannabinoid (CB)1 receptor antagonist AM251, or the CB2 receptor antagonist AM630. RESULTS:URB597 decreased leukocyte rolling and adhesion, as well as inflammation-induced hyperaemia. However, these effects were only apparent at low doses and the effects of URB597 were absent at higher doses. In addition to the anti-inflammatory effects of URB597, fatty acid amide hydrolase (FAAH) inhibition improved both hindlimb weight bearing and von Frey hair withdrawal thresholds. The anti-inflammatory effects of URB597 on leukocyte rolling and vascular perfusion were blocked by both CB1 and CB2 antagonism, while the effect on leukocyte adherence was independent of cannabinoid receptor activation. The analgesic effects of URB597 were CB1 mediated. CONCLUSIONS:These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these episodes.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Krustev E,Reid A,McDougall JJdoi
10.1186/s13075-014-0437-9subject
Has Abstractpub_date
2014-09-27 00:00:00pages
437issue
5eissn
1478-6354issn
1478-6362pii
s13075-014-0437-9journal_volume
16pub_type
杂志文章abstract:INTRODUCTION:Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4065
更新日期:2012-10-18 00:00:00
abstract::Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary gl...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3518
更新日期:2011-01-01 00:00:00
abstract::B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They are the source of the rheumatoid factors and anticitrullinated protein antibodies, which contribute to immune complex formation and complement activation in the joints. B cells are also very efficient antigen-presenting cells, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1010
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). METHODS:Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3926
更新日期:2012-07-25 00:00:00
abstract:INTRODUCTION:In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment. METHODS:Sequential blood lymphocyte subsets and LSG b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0750-y
更新日期:2015-09-04 00:00:00
abstract::A growing body of literature has demonstrated that the multifunctional glycoprotein osteopontin (OPN), has a role in type I interferon (IFN) production and may be involved in systemic lupus erythematosus (SLE) pathogenesis. A recent report has provided further support for this, demonstrating an association between rai...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4172
更新日期:2013-03-08 00:00:00
abstract::Lupus nephritis is a major contributor to morbidity and mortality in systemic lupus erythematosus, but little is known about the pathogenic processes that underlie the progressive decay in renal function. A common finding in lupus nephritis is thickening of glomerular basement membranes associated with immune complex ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2532
更新日期:2008-01-01 00:00:00
abstract::The discovery of the receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption exemplifies how both serendipity and a logic-based approach can identify factors that regulate cell function. Before this discovery in the mid to late 1990...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2165
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to ex...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1332-y
更新日期:2017-06-02 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-019-1982-z
更新日期:2019-08-29 00:00:00
abstract:INTRODUCTION:Soft tissue knee injury is a well-established and potent risk factor for development of knee osteoarthritis. However, there is a paucity of epidemiological data from the general population. Our aim was to estimate the annual person-level incidence for a wide spectrum of clinically diagnosed soft tissue kne...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4678
更新日期:2014-07-31 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is considered a T cell driven autoimmune disease, therefore, the ability of B cell depleting biologics, e.g., anti-CD20 antibodies, to alleviate RA is unclear. This study examined the proportions of IL-17-secreting lymphocytes in the blood of healthy subjects and RA patients and d...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3541
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to an...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/ar4184
更新日期:2013-02-26 00:00:00
abstract:INTRODUCTION:Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0724-0
更新日期:2015-08-12 00:00:00
abstract:INTRODUCTION:There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease, there is a need for relevant anim...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3172
更新日期:2010-01-01 00:00:00
abstract::Antibodies to double-stranded DNA are important in the pathogenesis of nephritis, a major clinical manifestation in lupus patients. Since earlier diagnosis of renal involvement may lead to better outcomes, identification of the nephritogenic specificity of lupus-associated autoantibodies is important in understanding ...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/ar2869
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC). METHODS:We developed an in vitro assay for RTX-CDC u...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4152
更新日期:2013-01-25 00:00:00
abstract:INTRODUCTION:Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2992
更新日期:2010-01-01 00:00:00
abstract::The difficulty in predicting the consequences of interactions between different cytokine networks has increased with the expansion of the T helper (Th) cell universe and the discovery of numerous B lymphocyte-derived cytokines. Consequently, it is now difficult to conceptualize a straightforward view of the contributi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3348
更新日期:2011-07-06 00:00:00
abstract:BACKGROUND:In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1147-2
更新日期:2016-10-22 00:00:00
abstract:INTRODUCTION:Brain-derived neurotrophic factor (BDNF) was first identified in the intervertebral disc (IVD) when its molecular upregulation was observed in sections of nucleus pulposus cultured under conditions of increased osmolarity. BDNF is now known to be involved in a number of biologic functions, including regula...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2456
更新日期:2008-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3830
更新日期:2012-05-02 00:00:00
abstract:INTRODUCTION:Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatmen...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar3054
更新日期:2010-01-01 00:00:00
abstract::Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4230
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to dis...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1323-z
更新日期:2017-05-31 00:00:00
abstract:INTRODUCTION:NLRP3 plays a role in sensing various pathogen components or stresses in the innate immune system. Once activated, NLRP3 associates with apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and procaspase-1 to form a large protein complex termed inflammasome. Although some ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4483
更新日期:2014-02-12 00:00:00
abstract::Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction distur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1848
更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1700-2
更新日期:2018-09-10 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02204-0
更新日期:2020-05-15 00:00:00
abstract::In a study published recently in Arthritis Research & Therapy, Woo and colleagues investigated the effects of pravastatin in combination with an apolipoprotein-AI (Apo-AI) mimetic peptide in a mouse model of lupus-accelerated atherosclerosis. Combination treatment resulted in a significant decrease in systemic inflamm...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3115
更新日期:2010-01-01 00:00:00