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Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain.
van Reij, RRI, Voncken, JW, Joosten, EAJ, van den Hoogen, NJ
Neurogenetics. 2020;(3):205-215
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Abstract
Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that has a substantial effect on quality of life. CPSP shows considerable clinical overlap with different chronic peripheral pain syndromes, suggesting a shared aetiology. This study aims to assess the genetic overlap between different chronic pain syndromes and CPSP, providing relevant biological context for potential chronic pain markers of CPSP. To analyse the genetic overlap between CPSP and chronic peripheral pain syndromes, recent GWAS studies were combined for polygenic risk scores (PRS) analysis, using a cohort of CPSP patients as starting point. Biological contextualisation of genetic marker, overlap between CPSP and chronic pain syndromes, was assessed through Gene Ontology (GO), using Pathway Scoring Algorithm (PASCAL) and REVIGO. PRS analyses suggest a significant genetic overlap between CPSP and 3 chronic pain disorders: chronic widespread pain (CWP, p value threshold = 0.003, R2 0.06, p = 0.003), rheumatoid arthritis (RA, p value threshold = 0.0177, R2 = 0.04, p = 0.017) and possibly sciatica (p value threshold = 0.00025, R2 = 0.03, p = 0.045). Whereas no significant genetic overlap was found with cluster headache and migraine, the outcome for osteoarthritis (OA) was inconsistent between the cohorts. This is likely related to cohort composition, as repeated random reallocation of patients' nullified CPSP/OA outcome variation between the discovery and replication cohorts. GO analyses suggested an aetiological involvement of genetic markers that control neurological signalling (specifically sodium channels) and inflammatory response. The current study reaffirms the impact of sample size, cohort composition and open data accessibility on the unbiased identification of genetic overlap across disorders. In conclusion, this study is the first to report genetic overlap between regulatory processes implicated in CPSP and chronic peripheral pain syndromes. Interaction between neurological signalling and inflammatory response may explain the genetic overlap between CPSP, CWP and RA. Enhanced understanding of mechanisms underlying chronification of pain will aid the development of new therapeutic strategies for CPSP with sodium channel biochemistry as a potential candidate.
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Unsaponifiable Fraction of Unripe Fruits of Olea europaea: An Interesting Source of Anti-inflammatory Constituents.
Gelmini, F, Ruscica, M, Macchi, C, Bianchi, V, Maffei Facino, R, Beretta, G, Magni, P
Planta medica. 2016;(3):273-8
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Abstract
The unsaponifiable fraction of olive oil from unripe fruits of Olea europaea at different stages of maturation (from 20 to 32 weeks after flowering) was analyzed by gas chromatography-mass spectrometry in order to select the time associated to the unsaponifiable fraction with the maximal yield in bioactive constituents. According to quantitative gas chromatography-mass spectrometry analysis, the unsaponifiable fraction (2.46% of the total oil) from olive fruits at the 22nd week was found to contain the maximal yield in anti-inflammatory constituents. Its composition was lanosterol (2.60 mg/g oil), stigmasterol (2.15), cycloartanol acetate (2.04), stigmastan-3,5-diene (2.01), obtusifoliol (1.93), cholesta-4,6-dien-3-one (1.42), α-amyrin (1.42), α-tocopherol (1.32), squalene (1.02), β-amyrin (0.57), and β-sitosterol (0.22). At later times, there was a decrease in the quantitative unsaponifiable fraction yield and a qualitative shift in the bioactive constituents. The 22nd week unsaponifiable fraction was subsequently incorporated into a topical preparation to be utilized for a small pilot clinical study in five patients affected by osteoarthrosis. According to clinical observation, the application of the ointment (three times daily for three weeks) attenuated hand and knee joint inflammatory features in all patients and was not associated to any adverse reactions.
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Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study.
Oben, J, Enonchong, E, Kothari, S, Chambliss, W, Garrison, R, Dolnick, D
Nutrition journal. 2009;:38
Abstract
BACKGROUND The objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis. METHODS An 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo were given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]). RESULTS Eighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 +/- 2.3 vs 11.8 +/- 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 +/- 1.4 vs 9.9 +/- 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 +/- 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups. CONCLUSION In this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contributing factor to the other benefits.
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Clinical and histopathological improvement of psoriasis with oral chondroitin sulfate: a serendipitous finding.
Vergés, J, Montell, E, Herrero, M, Perna, C, Cuevas, J, Pérez, M, Möller, I
Dermatology online journal. 2005;(1):31
Abstract
We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.
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[Influence of intra-articular injections of sodium hyaluronate on clinical features and synovial fluid nitric oxide levels of temporomandibular osteoarthritis].
Guarda Nardini, L, Oliviero, F, Ramonda, R, Ferronato, G
Reumatismo. 2004;(4):272-7
Abstract
OBJECTIVE This study was designed to assess the effect of intra-articular injection of sodium hyaluronate (SH) on clinical findings of temporomandibular osteoarthritis (OA) and on synovial fluid (SF) levels of nitric oxide (NO). METHODS Twenty seven patients (7 men, 20 women, mean (SD) age 53.9 (11.8) years) with OA of the temporomandibular joint were randomly allocated to receive an injection of either SH (2 ml, Hyalgan, Fidia SpA, Abano T., P.M. 500-700.000, 20 mg/2 ml; once a week for 5 weeks) or a Ringer's lactate solution (once a week for 3 weeks). Clinical evaluation was done before each procedure, and at 1 week, 1, 3 and 6 months post-injection. Intensity of temporomandibular joint pain, jaw function, maximal mouth opening and lateral jaw movements were recorded at each visit. NO was measured on SF collected by rinsing the joint with saline 1 ml before the treatment. RESULTS Injection of SH caused significant improvement in the main clinical symptoms until the last follow-up which was carried out 6 months after last injection. Among patients who received SH injection, those who reached a good outcome showed the lowest basal levels of NO. CONCLUSIONS The results of this study showed that intra-articular injections of SH lead to a lasting improvement in the clinical symptoms of temporomandibular OA. Furthermore, our findings suggest that low NO levels in SF are related to a better outcome of temporomandibular OA among patients treated with SH intra-articular injection.
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Randomized controlled trial of nettle sting for treatment of base-of-thumb pain.
Randall, C, Randall, H, Dobbs, F, Hutton, C, Sanders, H
Journal of the Royal Society of Medicine. 2000;(6):305-9
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Abstract
There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P = 0.026 and P = 0.0027).
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A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis.
Bliddal, H, Rosetzsky, A, Schlichting, P, Weidner, MS, Andersen, LA, Ibfelt, HH, Christensen, K, Jensen, ON, Barslev, J
Osteoarthritis and cartilage. 2000;(1):9-12
Abstract
OBJECTIVE Alternative medicine is used extensively by patients with chronic pain due to e.g., osteoarthritis. Only few of these drugs have be tested in a controlled setting and the present study was undertaken to examine the effect of ginger extract, one of the most popular herbal medications. DESIGN Ginger extract was compared to placebo and Ibuprofen in patients with osteoarthritis of the hip or knee in a controlled, double blind, double dummy, cross-over study with a wash-out period of one week followed by three treatment periods in a randomized sequence, each of three weeks duration. Acetaminophen was used as rescue medication throughout the study. The study was conducted in accordance with Good Clinical Practice (European Guideline for GCP). RESULTS A ranking of efficacy of the three treatment periods: Ibuprofen>ginger extract>placebo was found for visual analogue scale of pain (Friedman test: 24.65, P< 0.00001) and the Lequesne-index (Friedman test: 20.76, P< 0.00005). In the cross-over study, no significant difference between placebo and ginger extract could be demonstrated (Siegel-Castellan test), while explorative tests of differences in the first treatment period showed a better effect of both Ibuprofen and ginger extract than placebo (Chi-square, P< 0.05). There were no serious adverse events reported during the periods with active medications. CONCLUSION In the present study a statistically significant effect of ginger extract could only be demonstrated by explorative statistical methods in the first period of treatment before cross-over, while a significant difference was not observed in the study as a whole.