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.

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.

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.

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).

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.

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.