Refining surgical models of osteoarthritis in mice and rats alters pain phenotype but not joint pathology.

The relationship between osteoarthritis (OA) structural change and pain is complex. Surgical models of OA in rodents are often rapid in onset, limiting mechanistic utility and translational validity. We aimed to investigate the effect of refining surgical small rodent models of OA on both joint pathology and pain behaviour.

The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

Anxiety and depression are associated with increased pain responses in chronic pain states. The extent to which anxiety drives chronic pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing anxiety on future osteoarthritis (OA) pain was investigated, and potential mechanisms were studied in an animal model.

Potential audibility of ultrasonic signal monitoring of Public Address and Life Safety Sound Systems.

Ultrasonic surveillance monitoring, to check the operational integrity of Public Address (PA) and Emergency Communication Systems, has been in existence for over 40 years-particularly in Europe. Since its inception, there has been debate as to the potential audibility that these systems may have. As the vast majority of sound systems engineers and designers have not heard or experienced any effects, it has generally been assumed that the general public do not either.

Effects of carrageenan induced synovitis on joint damage and pain in a rat model of knee osteoarthritis.

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.

Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis.

Background: Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims of this study were to determine the influence of a passage number on the effects of MSCs on pain behaviour and cartilage and bone features in a rodent model of OA.

Methods: Rats underwent either medial meniscal transection (MNX) or sham surgery under anaesthesia.

Targeting the D Series Resolvin Receptor System for the Treatment of Osteoarthritis Pain.

Objective: Pain is a major symptom of osteoarthritis (OA); currently available analgesics either do not provide adequate pain relief or are associated with serious side effects. The aim of this study was to investigate the therapeutic potential of targeting the resolvin receptor system to modify OA pain and pathology.

Methods: Gene expression of 2 resolvin receptors (ALX and ChemR23) was quantified in synovium and medial tibial plateau specimens obtained from patients with OA at the time of joint replacement surgery.

Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA).

Objectives: To address the hypothesis that different types of established osteoarthritis (OA) pain behaviours have associations with different aspects of articular pathology, we investigated the relationship between structural knee joint pathology and pain behaviour following injection of a low vs a high dose of monosodium iodoacetate (MIA) in the rat.

Methods: Rats received a single intra-articular injection of 0.1 mg or 1 mg MIA or saline (control).

Histopathological subgroups in knee osteoarthritis.

Objective: Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features.

Design: Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations.

Robust anti-nociceptive effects of monoacylglycerol lipase inhibition in a model of osteoarthritis pain.

Background And Purpose: Chronic pain is often a symptom of knee osteoarthritis (OA) for which current analgesics are either inadequate or are associated with serious side effects. The endocannabinoid system may offer alternative targets for pain relief. We evaluated the effects of a potent and selective monoacylglycerol (MAG) lipase inhibitor (MJN110) on OA pain behaviour, spinal mechanisms of action and joint histopathology in the rat.

The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain.

Objective: Nerve growth factor (NGF) has a pivotal role in peripheral hyperalgesia and inflammation; anti-NGF antibodies attenuate pain responses in inflammatory pain models, and in people with osteoarthritis (OA) or low back pain. The aim of this study was to characterise the peripheral mechanisms contributing to the analgesic effects of anti-NGF antibody treatment in an established model of joint pain, which mimics key clinical features of OA.

Design: Effects of preventative vs therapeutic treatment with an anti-NGF antibody (monoclonal antibody 911: muMab 911 (10 mg/kg, s.

Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis.

Objectives: Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models.

Methods: Knee OA was induced in rats by intra-articular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline-injected or sham-operated controls.

Calcitonin gene-related peptide in the joint: contributions to pain and inflammation.

Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated.

Structural associations of symptomatic knee osteoarthritis.

Objective: Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA.

Methods: Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group).

Design, study quality and evidence of analgesic efficacy in studies of drugs in models of OA pain: a systematic review and a meta-analysis.

Objective: Studies using animal models are important in drug development, but often poorly predict treatment results in man. We investigated factors that may impact on the magnitude of the analgesic treatment effect in animal models of osteoarthritis (OA) pain.

Design: Systematic review of studies that measured behavioural pain outcomes in small animal models of OA, and tested drugs which reduce OA pain in man.

Differences in structural and pain phenotypes in the sodium monoiodoacetate and meniscal transection models of osteoarthritis.

Objectives: To characterize differences in joint pathology and pain behavior between two rat models of osteoarthritis (OA) in order to inform selection of animal models for interventional studies.

Method: Knee OA was induced in Sprague Dawley rats by either meniscal transection (MNX) or intra-articular injection of monosodium iodoacetate (MIA). Controls were subjected to sham surgery or saline-injection.

Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis.

Objectives: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined.

Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis.

During osteoarthritis (OA), angiogenesis is increased in the synovium, osteophytes and menisci and leads to ossification in osteophytes and the deep layers of articular cartilage. Angiogenic and antiangiogenic factors might both be upregulated in the osteoarthritic joint; however, vascular growth predominates, and the articular cartilage loses its resistance to vascularization. In addition, blood vessel growth is increased at--and disrupts--the osteochondral junction.

Lymphatic vessels in osteoarthritic human knees.

Objectives: The distribution and function of lymphatic vessels in normal and diseased human knees are understood incompletely. This study aimed to investigate whether lymphatic density is associated with clinical, histological or radiographic parameters in osteoarthritis (OA).

Methods: Sections of synovium from 60 knees from patients with OA were compared with 60 post mortem control knees (from 37 individuals).

A role for the sensory neuropeptide calcitonin gene-related peptide in endothelial cell proliferation in vivo.

Background And Purpose: We have tested the hypothesis that calcitonin gene-related peptide (CGRP) is a mediator of capsaicin-induced angiogenesis in vivo.

Experimental Approach: In a series of experiments, the knee joints of rats were injected with CGRP, capsaicin or vehicle control. Groups of animals (n=6) were treated with the CGRP receptor antagonist BIBN4096BS and/or the NK₁ receptor antagonist SR140333.

Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis.

Objective: To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA).

Methods: OA was induced in male Lewis rats (n=8 per group) by meniscal transection. Animals were orally dosed with dexamethasone (0.

Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis.

Objectives: Meniscal damage is a recognised feature of knee osteoarthritis (OA), although its clinical relevance remains uncertain. This study describes vascular penetration and nerve growth in human menisci, providing a potential mechanism for the genesis of pain in knee OA.

Methods: Menisci obtained post mortem were screened on the basis of high or low macroscopic tibiofemoral chondropathy as a measure of the presence and degree of OA.

Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis.

Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms.

Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitis.

Objective: To determine whether blood vessel growth at the onset of resolving synovitis leads to its subsequent persistence and whether inhibiting this angiogenesis at the onset of persistent inflammation leads to its subsequent resolution.

Methods: Inflammation and angiogenesis were induced by injection of 0.03% carrageenan and/or 6 pmoles of fibroblast growth factor 2 (FGF-2) into rat knees.

Effects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritis.

Objective: To investigate the effects of a matrix metalloproteinase (MMP) inhibitor on joint pathology and pain behavior in the rat meniscal transection (MNX) model of osteoarthritis (OA) and evaluate which aspects of structural disease modification contribute to symptom improvement.

Methods: OA pathology was induced in male Lewis rats, by transecting the medial collateral ligament with (MNX) or without (SHAM) a full thickness cut through the meniscus. MNX animals were orally administered an equipotent MMP 2, 8, 9, 12, 13 inhibitor (0.

Osteochondral angiogenesis and increased protease inhibitor expression in OA.

Objective: Normal cartilage is resistant to vascular invasion and anti-angiogenic protease inhibitors may contribute to its avascular status. We hypothesized that dysregulated expression of four key anti-angiogenic protease inhibitors may contribute to increased osteochondral vascularity in osteoarthritis (OA).

Design: Medial tibial plateaux from OA patients (n=40) were compared with those from non-arthritic controls collected post-mortem (PM, n=10).