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The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis.

ABSTRACT: OBJECTIVE:To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA). METHODS:The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile-Ile and risk of symptomatic and asymptomatic knee OA was assessed. RESULTS:The TRPV1 585 Ile-Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile-Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor ? and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue. CONCLUSIONS:A genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.

SUBMITTER: Valdes AM

PROVIDER: S-EPMC3147243 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis.

Valdes Ana M AM De Wilde Gert G Doherty Sally A SA Lories Rik J RJ Vaughn Frances L FL Laslett Laura L LL Maciewicz Rose A RA Soni Anushka A Hart Deborah J DJ Zhang Weiya W Muir Kenneth R KR Dennison Elaine M EM Wheeler Margaret M Leaverton Paul P Cooper Cyrus C Spector Tim D TD Cicuttini Flavia M FM Chapman Victoria V Jones Graeme G Arden Nigel K NK Doherty Michael M

Annals of the rheumatic diseases 20110525 9

<h4>Objective</h4>To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA).<h4>Methods</h4>The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile-Ile a ...[more]

PMID: 21616913

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Project description:BackgroundExperimental and clinical evidence support a link between body representations and pain. This proof-of-concept study in people with painful knee osteoarthritis (OA) aimed to determine if: (i) visuotactile illusions that manipulate perceived knee size are analgesic; (ii) cumulative analgesic effects occur with sustained or repeated illusions.MethodsParticipants with knee OA underwent eight conditions (order randomised): stretch and shrink visuotactile (congruent) illusions and corresponding visual, tactile and incongruent control conditions. Knee pain intensity (0-100 numerical rating scale; 0 = no pain at all and 100 = worst pain imaginable) was assessed pre- and post-condition. Condition (visuotactile illusion vs control) × Time (pre-/post-condition) repeated measure ANOVAs evaluated the effect on pain. In each participant, the most beneficial illusion was sustained for 3 min and was repeated 10 times (each during two sessions); paired t-tests compared pain at time 0 and 180s (sustained) and between illusion 1 and illusion 10 (repeated).ResultsVisuotactile illusions decreased pain by an average of 7.8 points (95% CI [2.0-13.5]) which corresponds to a 25% reduction in pain, but the tactile only and visual only control conditions did not (Condition × Time interaction: p = 0.028). Visuotactile illusions did not differ from incongruent control conditions where the same visual manipulation occurred, but did differ when only the same tactile input was applied. Sustained illusions prolonged analgesia, but did not increase it. Repeated illusions increased the analgesic effect with an average pain decrease of 20 points (95% CI [6.9-33.1])-corresponding to a 40% pain reduction.DiscussionVisuotactile illusions are analgesic in people with knee OA. Our results suggest that visual input plays a critical role in pain relief, but that analgesia requires multisensory input. That visual and tactile input is needed for analgesia, supports multisensory modulation processes as a possible explanatory mechanism. Further research exploring the neural underpinnings of these visuotactile illusions is needed. For potential clinical applications, future research using a greater dosage in larger samples is warranted.

Project description:BackgroundRecently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid.MethodsUsing hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years.ResultsOn the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5).ConclusionsSevere osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA.Trial registrationThe study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Project description:Background and aimGrowing attention is being given to utilising physical function measures to better understand and manage knee osteoarthritis (OA). The Fremantle Knee Awareness Questionnaire (FreKAQ), a self-reported measure of body-perception specific to the knee, has never been validated in Italian patients. The aims of this study were to culturally adapt and validate the Italian version of the FreKAQ (FreKAQ-I), to allow for its use with Italian-speaking patients with painful knee OA.MethodsThe FreKAQ-I was developed by means of forward-backward translation, a final review by an expert committee and a test of the pre-final version to evaluate its comprehensibility. The psychometric testing included: internal structural validity by Rasch analysis; construct validity by assessing hypotheses of FreKAQ correlations with the knee injury and osteoarthritis outcome score (KOOS), a pain intensity numerical rating scale (PI-NRS), the pain catastrophising scale (PCS), and the Hospital anxiety and depression score (HADS) (Pearson's correlations); known-group validity by evaluating the ability of FreKAQ scores to discriminate between two groups of participants with different clinical profiles (Mann-Whitney U test); reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation coefficient, ICC2.1); and measurement error by calculating the minimum detectable change (MDC).ResultsIt took one month to develop a consensus-based version of the FreKAQ-I. The questionnaire was administered to 102 subjects with painful knee OA and was well accepted. Internal structural validity confirmed the substantial unidimensionality of the FreKAQ-I: variance explained was 53.3%, the unexplained variance in the first contrast showed an eigenvalue of 1.8, and no local dependence was detected. Construct validity was good as all of the hypotheses were met; correlations: KOOS (rho = 0.38-0.51), PI-NRS (rho = 0.35-0.37), PCS (rho = 0.47) and HADS (Anxiety rho = 0.36; Depression rho = 0.43). Regarding known-groups validity, FreKAQ scores were significantly different between groups of participants demonstrating high and low levels of pain intensity, pain catastrophising, anxiety, depression and the four KOOS subscales (p ≤ 0.004). Internal consistency was acceptable (α = 0.74) and test-retest reliability was excellent (ICC = 0.92, CI 0.87-0.94). The MDC95 was 5.22 scale points.ConclusionThe FreKAQ-I is unidimensional, reliable and valid in Italian patients with painful knee OA. Its use is recommended for clinical and research purposes.

Project description:BackgroundThe global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pain thresholds (PPTs), facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM). As traditional analgesics (acetaminophen and non-steroidal anti-inflammatory drugs) are not recommended for long-term use in OA, more fundamental knowledge related to other possible management regimes are needed. Duloxetine is a serotonin-noradrenalin reuptake inhibitor, and analgesic effects are documented in patients with OA although the underlying fundamental mechanisms remain unclear. The descending pain inhibitory control system is believed to be dependent on serotonin and noradrenalin. We hypothesized that the analgesic effect of duloxetine could act through these pathways and consequently indirectly reduce pain and sensitization. The aim of this mechanistic study is to investigate if PPTs, TSP, CPM, and clinical pain parameters are modulated by duloxetine.MethodsThis proof of concept study is a randomized, placebo-controlled, double-blinded, crossover trial, which compares PPTs, TSP, and CPM before and after 18 weeks of duloxetine and placebo in forty patients with knee OA. The intervention periods include a titration period (2 weeks), treatment period (60 mg daily for 14 weeks), and a discontinuation period (2 weeks). Intervention periods are separated by 2 weeks.DiscussionDuloxetine is recommended for the treatment of chronic pain, but the underlying mechanisms of the analgesic effects are currently unknown. This study will investigate if duloxetine can modify central pain mechanisms and thereby provide insights into the underlying mechanisms of the analgesic effect.Trial registrationClinicalTrials.gov NCT04224584 . Registered on January 6, 2020. EudraCT 2019-003437-42 . Registered on October 22, 2019. The North Denmark Region Committee on Health Research Ethics N-20190055. Registered on October 31, 2019.

Dataset Information

The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis.

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The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis.

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