No description available.

Background: Pain is the main reason patients present with Osteoarthritis (OA). There are many risk factors for increased pain but one risk factor that is the focus of this thesis is catastrophizing. There is a discrepancy between the amount of radiographic damage to the joint and the pain intensity felt by the OA patient, which leads to the hypothesis that there must be other non-structural factors such as catastrophizing that could explain this discrepancy. Objectives: (1) To assess the effect of catastrophizing on joint and body pain in individuals who have undergone total joint replacement surgery after accounting for sleep quality, anxiety and depression in people diagnosed with large joint OA and controls. X-rays and resulting K/L grade also used to account for joint damage. (2) To identify if there are specific genes and pathways that could explain the relationship between catastrophizing and pain, also whether catastrophizing is a trait in its own right which is not dependent on depression or bad quality sleep. (3) To identify genetic factors which contribute to the effect of catastrophizing on pain intensity in OA by comparing those with symptomatic OA to those with asymptomatic OA. Methods: Pain post- Total Joint Replacement (TJR) (Chapter 3): This is a case-control study design. Cases were derived from the Nottingham genetics of OA study (NGOAS) and the Genetics of Osteoarthritis and Lifestyle Study (GOAL) cohorts that have undergone joint replacement. Controls were derived from participants in the GOAL cohort that were selected as controls for OA. 1093 individuals from the NGOAS cohort who had been diagnosed with knee or hip OA were recruited from secondary care (82% post-total joint replacement (TJR) none on waiting list) and completed a questionnaire which included items on: joint pain, neuropathic pain like symptoms (using the painDETECT questionnaire), anxiety (using the hospital anxiety and depression scale (HADS) questionnaire), depression (using the HADS questionnaire) and the 13-item pain catastrophizing scale (PCS). A similar questionnaire was sent to participants from a case control OA study known as the GOAL involving 679 cases all with hip or knee OA (59.7% post-TJR, none on waiting list) and 402 non-OA controls. TJR used as cases due to this being the end point of OA with those undergoing TJR most likely in pain from OA. High pain catastrophizing was defined as being in the top tertile of the PCS (score≥9). SPSS was then used to calculate descriptive statistics such as percentage of participants that were female, mean age, BMI. This would give a picture of the cohort being used. Then binary logistic regressions were used to calculate odds ratios (ORs) for sleep, depression, anxiety and catastrophizing whilst adjusting for confounding factors such as age, BMI, gender. Genetics (Chapter 4 and 5): Quantile-Quantile (QQ) and Manhattan plots were produced using R to quality test the genomic data. A Manhattan plot is a type of scatter plot, usually used to display data with a large number of data-points - many of non-zero amplitude, and with a distribution of higher-magnitude values, for instance in genome-wide association studies (GWAS). The statistics program R (version 3.0.2) was used to create Manhattan and QQ plots using the “ggplot2” library and “qqplot” script. A genome wide association scan (GWAS) and single nucleotide polymorphism (SNP) extractions, conducted using Plink, were carried out on a subset of 1113 post TJR cases from the NGOAS cohort and pathway analysis was then conducted based on significant SNPs found in the GWAS. In chapter 4 replication and meta-analysis were then carried out using a separate cohort of 679 participants, taken from the GOAL study. Results: Pain post- total joint replacement (TJR) (Chapter 3): The prevalence of high catastrophizing was not significantly higher in OA and post TJR cases (36.8%) than in controls (33.1%)(p<0.07), however as controls were from intravenous urography (IVU) clinics they would have higher levels of cardio-vascular disease, stroke, kidney disease for example than general population. The main factors associated with catastrophizing were older age, higher body mass index, high pain intensity, anxiety, depression and multiple regional pain. High catastrophizing was associated with increased risk of severe joint (hip or knee) pain after adjustment for sleep quality, anxiety and depression (OR= 2.99, 95% CI= 2.20-4.04, p< 1.54E-12). Similarly, high catastrophizing was associated with body pain (OR=1.47, CI=1.16-1.86, P<0.0002) and neuropathic-like pain symptoms (OR=5.35, CI=4.16-6.90, P<1.42E-35). I also explored if these associations with pain were due to the presence of comorbidities which are common in OA patients and post-TJR. I did find that pain catastrophizing scores were also associated with cardiovascular disease (CVD) after adjustment for depression and sleep quality as well as BMI, age and gender (OR= 1.44, 95% CI= 1.14-1.81, p< 0.001). Genetics (Chapter 4 and 5): Several SNPs were linked to high catastrophizing scores with a p-value <0.00005. ADRA2C was the only gene associated with catastrophizing that replicated in chapter 4 after meta-analysis. This variant was associated with OR=0.67, 95% CI= 0.56-0.80, p-value=7.8x10[-6]. It is involved in the formation of adrenergic receptors and therefore the regulation of possibly many pain pathways including the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis as well as being required for normal presynaptic control of transmitter release in the heart. PRR20 was another interesting finding in chapter 4. It is involved in dopamine receptors, so possibly influencing that particular pain pathway. These data demonstrate that catastrophizing does influence pain intensity and implicates certain molecular pathways that may be involved in this relationship. LEPRE1 and COL6A1 are both implicated in chapter 5. Both of these genes are involved in collagen formation and destruction thereby could affect the progression of OA and joint structure leading to pain. LEPRE1 is further known as one of the genetic causes of Osteogenesis imperfecta type VIII another bone formation disorder. Conclusion: Pain catastrophizing is associated with joint and body pain in individuals with OA after TJR and this effect is not mediated by sleep quality, anxiety or depression. Therefore catastrophizing can be said to be a trait in its own right. Many genes and pain pathways were implicated by the genetics studies, mainly involving adrenaline and dopamine, so more focus on these neurotransmitters could be suggested for future study. Another interesting finding that could be investigated further is the link between cardiovascular disorders and catastrophizing as this is a relatively unexplored area, made more interesting by the finding of ADRA2C both indicating involvement of the sympathetic nervous system and other central mechanisms.

Background: Fragility hip fractures among the elderly constitute a significant global public health problem. The disease is devastating for both patient and the family, often resulting in reduced mobility (disabling), increased reliance on others, diminished health and quality of life, and sometimes death. Thirty-day and one-year mortality rates are high. Postoperative morbidity and ‘delayed discharges’ are frequently cited with an average length of hospital stay of 19.5 days. Aim: This project aimed to assess impact of current perioperative care on patient outcome after hip fracture surgery. Methods: A systematic review was performed to identify currently available risk stratification tools used in hip fracture patients. The NHFS and SORT scoring tools were evaluated and recalibrated. A mixed methods study to identify public (patients, relatives and healthcare professionals) perceptions on factors delaying discharge was conducted and a cohort follow up study of 341 patients to develop and validate a Hip Fracture postoperative morbidity survey tool (HF-POMS). Results and conclusion: The NHFS and SORT performed better than other risk stratification tools in the literature; however, they both needed further validation. Five key factors of importance identified by the public affecting LOS were; medical conditions (both prefracture comorbidities and postoperative complications), age and frailty, the recovery process (mobility and rehabilitation) psychological aspects and social factors. A 12- domains validity tool (HF-POMS) was developed with kappa interrater reliability of 0.68. High morbidity presence was seen in the following domains; renal, assisted ambulation, pain and infectious. Presence of any morbidity on postoperative days 8 and 15 was associated with subsequent LOS of 3.08 days (95% CI 0.90 – 5.26, p= 0.005) and 15.81 days (95% CI 13.35 – 18.27, p = 0.001) respectively. The average LOS was 16.9 days. The HF–POMS is a reliable and valid tool for measuring immediate postoperative complications in hip fracture patients. Many patients remained in hospital for non-medical reasons.

No description available.

Osteoarthritis pain is a major cause of long-term disability and chronic pain in the adult population, which can lead to reduced quality of life and serious comorbidities such as depression. Together with the substantial burden chronic osteoarthritis pain (COAP) causes at the individual level, associated economical costs are alarming and set to rise given the ageing population. Yet there are very few effective treatments available, which include both pharmacological and non-pharmacological options. Around one in five COAP patients do not receive satisfactory pain relief, even after undergoing joint replacement surgery. This strongly supports the notion that chronic osteoarthritis pain has a central component, and reflects the need for improved understanding of neural mechanisms of chronic pain and chronic pain relief. Substantial advances have been achieved over the past two decades towards unravelling the role of the central nervous system in predisposition, development and maintenance of chronic pain. Despite these efforts, there is still a major gap in integrating these advances and translating them into more meaningful treatments. The studies presented here endeavour to shed light on these aspects by capturing multidimensional contributions from brain mechanisms, negative mood and pain characteristics to COAP and to the effect of treatment, with the overall aim of improving current understanding of central components of this condition and mechanisms of centrally acting analgesic treatment. More specifically, the principal objectives consist of: 1. Identifying markers indexing neuroplasticity changes linked with COAP, and molecular mechanisms in COAP; 2. Studying neural correlates of the analgesic effects of opioids, the strongest pain killers available, in individuals with COAP and explore whether pain phenotyping may predict the extent of treatment response; 3. Assessing the neural effects of the antidepressant duloxetine and investigating potential predictors of treatment outcome. In order to achieve these objectives four studies are undertaken. First, the microstructure of the brain in chronic osteoarthritis pain is investigated in a cross-sectional manner in 46 individuals (23 COAP), in an attempt to identify potential signs of structural neuroplasticity. Analysis of cerebral microstructure with diffusion imaging techniques is sensitive to minor changes in myelination and axonal loss, thus being a plausible marker of neuroplasticity. Second, in a similar study design, the brain of 39 participants (20 COAP) is examined on the molecular level, focusing on neurotransmitter levels within one key region involved in pain, namely the anterior cingulate cortex (ACC). Using the setting of randomised controlled trials (RCT), the third and fourth projects are planned and developed, with novel investigational protocols being established before recruitment takes place. Previously established multi-modal structural, blood oxygen level dependent (BOLD), and blood flow imaging of the brain are included, in addition to novel task-related functional paradigm and quantitative sensory testing. Study three consists of a mechanistic, saline controlled, acute intervention study of remifentanil involving 28 individuals with COAP, while a sub-chronic placebo controlled investigation of duloxetine (77 COAP) constitutes study four. Remifentanil is a μ−opioid agonist, a strong analgesic, while duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI), novel class of antidepressants. All four studies are performed at 3T. No abnormalities in brain structure were found in association with COAP, but an inverse correlation between ACC -aminobutyric acid levels and pain severity was seen, which was not dependent on negative affect or age, explaining nearly 60% of the variance. Pinprick-related BOLD activity in COAP was characterised and partially modulated by the opioid remifentanil, preferentially in patients with more impaired conditioned pain modulation (CPM). 77 participants consented into study four. Fifty-six participants completed the study, from which 34 received duloxetine treatment for 6 weeks, while 22 received placebo equivalent. Around half (53%) of duloxetine intakers reported clinically meaningful pain relief, against 36% of placebo intakers. Interim analysis of the effects of duloxetine on pinprick-related activity did not detect activity changes, albeit lower baseline anterior insula activity showed association with better treatment outcomes after duloxetine, but not placebo. Additionally, responders to either duloxetine or placebo had a tendency for lower ACC activity prior to treatment. These results suggest that, differently from other chronic pain conditions, such as back pain and fibromyalgia, COAP is not accompanied by major apparent structural reorganisation nor abnormal ACC neurotransmitter levels. However they also indicate some shared mechanisms between COAP and fibromyalgia, given cingulate GABA encoding of perceived pain severity, which supports use of GABA levels as a marker for mechanistic evaluation of GABAergic modulation for pain relief in COAP. The observed absence of structural abnormalities in COAP, suggests that this condition may be simpler to treat than other types of chronic pain. The GABA association seen in COAP, and previously shown in fibromyalgia, indicates that certain mechanism-based drugs may be useful for both COAP and other conditions. Results from the opioid study, in conjunction with the published literature suggest shared neural mechanisms of opioidergic analgesia between chronic pain states and the healthy state. Additionally, they point out that CPM might allow prediction of the need for centrally acting drugs. In the duloxetine study however, CPM was not related with differential treatment outcomes. Instead the anterior insula seem to play a role in determining the likelihood of clinically meaningful treatment response to duloxetine. However, results from both these analgesic studies must be interpreted with caution as they were based on a sub-sample of the full dataset acquired, as recruitment was still ongoing. Both RCTs have now been completed, and analyses of the full dataset is ongoing. Collectively, findings in this dissertation provide new evidence to the field of chronic pain research, suggesting that the structural and neurochemical brain reorganisation seen in other chronic pain conditions are likely pain-type specific, besides some partially overlapping mechanisms which are characterised here. The analyses of the RCTs of opioid and SNRI treatments, albeit preliminary, elucidate some putative mechanisms and predictors of centrally-mediated analgesia in COAP. Nevertheless, the full dataset, based on the rich methodology and protocols developed as part of the PhD, which is now available and undergoing investigation, should allow firmer conclusions regarding these two major classes of drugs and placebo in chronic pain.

No description available.

Background: Knee pain, the main symptom of knee osteoarthritis (OA), affects one in 4 people aged over 55 years, of whom 10% have mild to moderate disability. The aetiology of knee pain is heterogeneous and its relationship with structural changes and function is unclear. An important role for synovial pathology in the initiation and progression of knee OA has been emphasised. However, the normal values of synovial changes detected on ultrasound (US) in the general population and their association with knee pain in community-based people with knee pain or OA remain largely unknown. Objectives: [1] to systematically review the literature on synovial changes detected on US in people with knee pain/OA and/or in the general population. [2] to establish the normal ranges for synovial thickness and effusion and determine an optimal cut-off associated with knee pain and radiographic osteoarthritis (ROA) in community-derived men and women over 40 years old. [3] to examine whether community-derived people with early and chronic established knee pain have different risks of having effusion, synovial hypertrophy and Power Doppler signal (PDS), and to explore whether synovial changes detected on US predict/associate with subsequent knee pain worsening. [4] to explore the role of peripheral and central risk factors of knee pain, including the role of synovial changes detected on US in different types of knee pain. Methods: A systematic literature search was undertaken in Medline, EMBASE, Allied and Complementary Medicine, PubMed Web of Science, and SCOPUS databases in May 2015. Frequencies of US abnormalities in people with knee OA/pain, in the general population or asymptomatic controls were pooled using the random effects model. Publication bias and heterogeneity between studies were examined. The source population was the Knee Pain and Related Health in the Community (KPIC, n=9506) survey in Nottingham, UK. All participants had bilateral US and radiographic examination. Synovial changes detected on US were measured by two observers (inter-observer concordance correlation was 0.8 (0.6 to 0.9) for effusion and 0.7 (0.5 to 0.9) for synovial hypertrophy). OA structural changes were measured by standardised radiographs (semi-flexed weight-bearing and flexed skyline views) using the Nottingham Line Drawing Atlas (NLDA). A cross-sectional study comprised of 299 randomly selected adults ≥40 years old (147 women, 152 men). The normal range (95% quintile) for effusion and synovial hypertrophy was calculated in the healthy sample (no current knee pain and no ROA, n=163). The optimal cut-off was established using ROC curve analysis. A case-control study compared community-derived participants with early knee pain (n=298), chronic established knee pain (n=100) and no knee pain (n=94) at baseline. 166 early knee pain participants were followed-up at one year for changes in knee pain and synovial changes detected on US. Relationships between changes in synovial changes detected on US and pain severity were examined using correlation analysis. 255 participants with early and established knee pain replied to a one-year follow-up questionnaire. Predictors of knee pain worsening were determined using logistic regression. Central and peripheral risk factors for knee pain were examined using participants from both the cross-sectional and case-control studies (n=736). The contribution of each was presented using ROC curves. Subgroup analysis was undertaken according to the presence/absence of ROA and widespread pain (WSP) for the association between synovial changes detected on US and knee pain. A within-person analysis in participants with unilateral knee pain was also undertaken. Results:Systematic review and meta-analysis: 29 studies (4720 patients) were identified from the literature. The pooled prevalence of US effusion, synovial hypertrophy and PDS in people with knee OA/pain were 51.5% (95%CI 40.2 to 62.8), 41.5% (26.3 to 57.5) and 32.7% (8.34 to 63.24), respectively, which were higher than those in the general population or asymptomatic controls (19.9% (95%CI 7.8 to 35.3), 14.5% (0 to 58.81), and 15.8% (3.08 to 35.36), respectively). People with knee OA (ACR criteria or ROA) had greater prevalence of synovial changes detected on US than people with knee pain (p=0.037, p=0.010 and p=0.009, respectively). Cross-sectional study: Synovial changes detected on US were different between men and women, therefore, gender-specific reference limits were estimated. In people without KP and structural OA the normal range for effusion was between 0 to 10.3 mm for men and between 0 to 9.8 mm for women and the normal range for synovial hypertrophy was between 0 and 6.8 mm for men and between 0 and 5.4 mm for women. The effusion cut-off able to distinguish a subgroup of people with knee pain and ROA (i.e. “symptomatic OA”) with high specificity was 8.9 mm for men and 7.8 mm for women, and for synovial hypertrophy it was 5.8 mm for men and 4.2 mm for women. Case-control study: At baseline, effusion was associated with early (OR 2.64, 95%CI 1.57 to 4.45) and established KP (OR 5.07, 95%CI 2.74 to 9.38). Synovial hypertrophy was also associated with early (OR 5.43, 95%CI 2.12 to 13.92) and established KP (OR 13.27, 95%CI 4.97 to 35.43). However, the association with effusion diminished when adjusted for ROA. PDS was uncommon (early KP 3%, established KP 2%, controls 0%). Changes in effusion or synovial hypertrophy did not correlate with changes in KP in one year. Effusion and ROA predicted worsening of knee pain at one year (aOR 1.95, 95% CI 1.05 to 3.64, and aOR 3.52 95%CI 1.37 to 9.09, respectively). Central versus peripheral risk factors: A number of central and peripheral risk factors associated with knee pain, including WSP, pain catastrophising, knee injury, ROA, effusion and synovial hypertrophy. Although 25% of knee pain was explained by peripheral risk factors, only 5% was explained by central risk factors. Knee pain was stratified into 4 subgroups according to ROA and WSP. The association between synovial changes detected on US and knee pain varied between subgroups, being strongest in people with isolated ROA (e.g., aOR for hypertrophy 9.99, 95%CI 5.06 to 19.03), moderate in people with ROA plus WSP (aOR 7.24, 95%CI 3.04 to 17.25), weak in people with neither ROA nor WSP (aOR 2.25, 95%CI 1.19 to 4.22) and statistically insignificant in people with isolated WSP (aOR 2.21 95%CI 0.99 to 4.93). This was confirmed by the “one-person two knee” analysis where WSP was fully balanced between painful knees and pain-free knees. The association between synovial changes detected on US and knee pain was stronger when the knees had underlying structure OA changes. Conclusions: Effusion and synovial hypertrophy but not PDS are common in community-derived people with knee pain. These features differ in men and women, requiring different thresholds for abnormality. Synovial changes detected on US are associated knee pain, especially in people with ROA but no WSP. However, changes in effusion and synovial hypertrophy do not correlate with changes in knee pain, and effusion but not synovial hypertrophy predicts pain progression at one year. Further study of the causality between synovial changes detected on US and structural OA, and between peripheral and central risk factors for knee pain is needed.

Cette étude porte sur l’œuvre entière de Kuki Shûzô (1888-1941), non seulement sur sa pensée de la contingence, ses théories de la rime et du temps, son essai sur l’iki (idéal éthique et esthétique de l’époque d’Edo), mais aussi sur ses déclarations d’ordre politico-culturel sur l’ethnie (minzoku) et la guerre. Essai d’histoire de la philosophie japonaise, elle se propose de présenter et d’approfondir les dialogues que Kuki a entretenus, parfois directement, avec l’Europe philosophique de l’époque (notamment Bergson et la phénoménologie), mais aussi avec les philosophes japonais (notamment Watsuji et Tanabe) et un monde intellectuel plus large (le « mouvement pour la culture » de l’ère Taishô, les discussions sur la poésie japonaise, le débat sur la « littérature du hasard »), dialogues à partir desquels les concepts de Kuki ont émergé. Nous interprétons son œuvre en mettant en valeur une tension entre insistance sur le « concret donné » et logique de l’identité. Avancé par Kuki contre l’idée d’universel abstrait, le concret donné est incarné par plusieurs figures du « nous », du commun, qui se caractérisent par la différence avec autrui : l’ethnie, la coexistence intersubjective de l’iki, la rencontre contingente entre individus, dont nous donnons une interprétation phénoménologique. La logique de l’identité est présente dans l’idée d’identité ethnique, la métaphysique de l’éternel retour du même et la praxis de l’assimilation d’autrui dans l’identité du moi. Nous élucidons la manière dont Kuki systématise cette tension, ainsi que les conséquences de cette systématisation sur les questions éthique et politique de la communauté et des rapports entre individu, nation et monde. / This study focuses on Kuki Shûzô’s entire oeuvre: not only on his theories of contingency, rhyme, and time, and his essay on iki (the ethical and esthetical ideal of Edo period), but also on his cultural-political assertions on ethnic people (minzoku) and war. This essay on history of Japanese philosophy tries to present and develop dialogues that Kuki maintained, sometimes directly, with European philosophers of the time (in particular Bergson and the phenomenologists), but also Japanese philosophers (in particular Watsuji and Tanabe) as well as the broader intellectual world (the “movement of culturalism” of the Taisho era, debates on Japanese poetry and the “literature of contingency”). It was from these dialogues that Kuki’s concepts emerged.I interpret his oeuvre by emphasizing tensions between insistence on the “given concrete” and the principle of identity. Claimed by Kuki against the idea of an abstract universal, the given concrete is embodied by several figures of “we”, of the common, which are characterised by difference with others: ethnic people, intersubjective coexistence of iki, the contingent encounter between individuals, of which I give a phenomenological interpretation. Logic of identity is represented by the idea of ethnic identity, the metaphysics of eternal return of the same, and the praxis of assimilation of others in the identity of the “I”. I clarify the way Kuki systematizes this tension, as well as the consequences of this systematization on ethical and political problems of community and relationships between the individual, nation, and world.

Chronic pain is a complex experience that involves sensory, emotional, and cognitive aspects. The neurobiological mechanisms are therefore expected to be complex, widespread and largely maladaptive. Recent research of neuroimaging in chronic pain suggests cerebral re-organization on a structural level as a consequence of chronic pain. However, a combined and large-scale brain morphological profile in chronic pain to investigate its neural substrates has not been elucidated. The research presented aims to investigate morphological brain correlates and putatively related behavioural and cognitive aspects of chronic pain due to primary nociceptive knee osteoarthritic disorder using advanced imaging techniques for manual, voxel-based, and surface-based analysis, and questionnaire-based participants’ characterization. 31 participants with chronic painful knee osteoarthritis (age= 64.6± 8.4 years, 15 females, mean duration of pain=9.6 years) and 22 healthy controls (age= 61.3± 7.5, 13 females) underwent high-resolution anatomical MRI at 3 Tesla, and detailed pain characterization and psychometric assessment. Findings from this thesis challenge the common belief that chronic pain leads to hippocampal volume reduction and allegedly cognitive dysfunction. Indeed, general cognitive function and delayed recall memory were normally preserved in the studied cohort, and moreover the hippocampal volume was significantly enlarged. The volume of the rostral part (emotional) of anterior cingulate showed significant positive correlation with pain catastrophizing behaviour suggesting that it may underlie the pain catastrophizing tendency in patients with chronic knee pain. Higher scores of mechanical pain sensitivity correlated with reduced cortical thickness in the anterior cingulate indicating its potential key role in the process of central pain sensitization. Sufferers of chronic knee OA pain exhibited less grey matter volume in the left dorsolateral prefrontal cortex, which has a modulatory role in nociceptive transmission namely, pain perception inhibitory effect. Although the mechanism of this reduction is unknown, such a change may suggest functional disturbance with subsequent aberrant contribution to pain sustainability and chronification. Whole brain cortical thickness was investigated in patients and results revealed wide spread cortical thinning progresses with pain duration, preferentially in females, and in areas largely outside the known pain matrix, but including the posterior default mode network. Finally, preliminary results from investigating the potential mechanism of chronic pain related neocortical plasticity will be presented that may provide framework for future studies.

Background: Despite the extensive research into the pathophysiology of osteoarthritis (OA), pain still represents a significant unmet clinical need. This thesis explores the effects of a tropomyosin related kinase A receptor (TrkA) inhibitor and an anti-nerve growth factor (NGF) antibody as interventions to modify inflammation, structural pathology and pain behaviour in rat models of OA. Methods: Rat models of OA (monosodium iodoacetate - MIA and medial meniscal transection – MNX) were assessed for pain behaviour and pathology. Effect of interventions on pain behaviour (weight bearing asymmetry and paw withdrawal thresholds) and structural pathology (macroscopic and microscopic scoring of articular surfaces) to include inflammation were assessed using inhibitors of the NGF-TrkA pathway. Pain Data were analysed longitudinally using area under the curve or independently with Kruskal Wallis test followed by Dunns post hoc. Other data were analysed with Kruskal Wallis test followed by Dunns post hoc. Results: The MIA and MNX models all exhibited inflammation and pain behaviour. The MIA and MNX models displayed both macroscopic and microscopic pathology. Following preventive or therapeutic treatment with the tropomyosin receptor kinase (Trk) A inhibitor AR786, pain behaviour was inhibited in both MIA and MNX models. Synovitis was attenuated only in the MIA model. Analgesia was sustained for up to 10 days in the MNX model following AR786 treatment discontinuation. Preventive and therapeutic treatment with the anti–NGF monoclonal antibody M911 did not alter changes to cartilage pathology. Conclusions: Manifestation of pain, inflammation and alterations in knee joint structure are characteristic features of OA models. NGF might contribute to OA pain through the NGF-TrkA pathway. This contribution might be as a result of facilitating nociception, and inflammation. Further investigation into the mechanisms by which NGF contributes to OA pain through the TrkA receptor might increase therapeutic potential for OA chronic pain relief.