Decrease In Joint Pain Research Articles

Is platelet-rich plasma effective for osteoarthritis?

Despite varied non-surgical alternatives for the treatment of osteoarthritis, many patients remain symptomatic. In the last decade, the use of intra-articular platelet-rich plasma (PRP) has been proposed as an option. However, there is controversy about its clinical benefit and safety. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We identified twelve systematic reviews including four studies overall, of which all corresponded to randomized trials. We concluded that intra-articular injection of platelet-rich plasma might slightly decrease joint pain and improve patient satisfaction,vut it is not clear whether it has any effect on functionality because the certainty of the evidence is very low. As for the adverse effects, if they exist, they would be non-severe and self-limited.

ERGONOMIC EXERCISES TO DECREASE JOINT PAIN SCALE AND MUSCLE STRENGTH IN ELDERLY

Introduction. Epidemiological data showed an increased prevalence of chronic pain and weakness in the elderly. Nonpharmacological modality therapy is a component of multi modal management that very important for pain management, including Ergonomic Exercises. The aims of the study was to determine the effect of activity therapy ergonomic exercises to decrease joint pain scale, and to increase muscle strength in elderly with joints degenerative. Method. Quasi-experimental with pretest-posttest control group design was carried out in this study. Purposive sampling was used to identify the study subjects. A sample of 50 elderly was included in the study for experimental (17) and control (33) groups. Sampling technique used purposive sampling. T-test, Wilcoxon, and two sample Wilcoxon rank-sum, tests were used to analysis the data. Results. During the four weeks intervention of ergonomic exercise, there were significant decreases in scale joint pain in elderly with degenerative joint by P value 0.000 (α < 0.05), and increases in muscle strength by P value 0.002 for muscles pull and P value 0,0001 for muscles push. Discussion. Activity therapy of an ergonomic exercise has significant influence to decrease joint pain scale and to increase muscle strength in elderly with degenerative joints.Keywords: joint degenerative, elderly, joint pain, muscle strength, ergonomic exercises

The Impact of Lipid Types and Liposomal Formulations on Osteoblast Adiposity and Mineralization.

Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Lipids are common constituents in supramolecular vesicles (e.g., micelles or liposomes) that serve as drug delivery systems. Liposomal formulations such as Meriva® were proven to decrease joint pain and improve joint function in osteoarthritis (OA) patients. In this study, we evaluated how lipid types and liposomal formulations affect osteoblast behavior including cell viability, differentiation, mineralization and inflammation. Various liposomal formulations were prepared using different types of lipids, including phosphatidylcholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE), cholesterol (Chol), 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol HCl), and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) to investigate the impact on osteoblast differentiation and inflammation. The results indicated that cationic lipids, DC-cholesterol and DOTAP, presented higher dose-dependent cytotoxicity and caused high level of inflammatory responses. Due to the natural properties of lipids, all the lipids can induce lipid droplet formation in osteoblasts but the level of lipid droplet accumulation was different. In comparison with cationic lipids, neutral lipids induced less adiposity, and maintained high osteoblast mineralization. Similar to previous researches, we also confirmed an inverse relationship between lipid droplet formation and osteoblast mineralization in 7F2 mouse osteoblasts. Importantly, PC containing liposomes (PC only and PC/DOTAP) suppressed IL-1β-induced gene expression of COX-2 and MMP-3 but not Chol/DOTAP liposomes or DC-Chol/DOPE liposomes. Taken together, we suggested that PC contained liposomes could provide the best liposomal formulation for the treatment of bone diseases.

Five-Year Follow-up of a Longitudinal Cohort Study of the Effectiveness of Functional Electrical Stimulation for People with Multiple Sclerosis.

Few studies have examined the long-term consequences of using peroneal nerve functional electrical stimulation (FES) for people with multiple sclerosis (MS). This study examines orthotic effects on a longitudinal cohort and explores additional benefits of FES on self-reported measures such as joint pain. One hundred forty-five people with foot drop and MS were included (mean age, 52 [range, 28-74] years). Orthotic effects, unassisted walking speed, and clinically important differences (ie, ≥0.05 and ≥0.10 m/s) were derived from walking speed over 10 m. Visual analogue scales examined joint pain, walking effort, trips, confidence, and quality of life. Measures were taken on day 1, after 6 months, and at 2, 3, 4, and 5 years. A significant difference was found overall for walking with FES compared with walking without FES for the 5-year period (P < .001). Despite a significant decline in overall unassisted walking speed at baseline (0.58 m/s) compared with 5 years later (0.46 m/s) (P < .001), participants achieved an orthotic effect with (0.52 m/s) versus without (0.46 m/s) FES after 5 years (P < .001). A significant decrease in joint pain was found after 6 months compared with day 1 (P = .004), which was maintained after 5 years (P < .001). Despite progression of MS, long-term users of FES still benefit from an orthotic effect after using FES for 5 years. The study highlights the need for further work to assess the perceived benefits of FES regarding the experience of joint pain.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

BackgroudWhole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)–induced knee osteoarthritisrabbit model.MethodNinety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.ResultsAfter 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.ConclusionOur data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Effect Of Low-magnitude Different-frequency Whole-body Vibration On Subchondral

PURPOSE: To investigate the effects of different vibration frequencies of low-magnitude whole-body vibration (WBV) on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and jointpain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritis(OA) rabbit model. METHODS: Ninety adult rabbits subjected to unilateral ACLT were divided into six groups:Group 1,ACLT control group;Group 2,WBV (5 Hz) + ACLT;Group 3,WBV (10 Hz) +ACLT;Group 4,WBV (20 Hz) + ACLT;Group 5,WBV (30 Hz);and Group 6,WBV (40Hz).Pain was tested via weight-bearing asymmetry.Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]).Serum bone-specific alkaline phosphatase,N-mid OC,cartilage oligometric protein,CPII,type I collagen,PIIANP,G1/G2 aggrecan levels, and urinary CTX-II were analyzed. RESULTS: After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz group. CONCLUSIONS: Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain.

Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production invivo and determine its efficacy in animal models of musculoskeletal pain. Compound libraries were screened using an LPC coupled enzyme assay that measures the amount of choline released from LPC by the action of autotaxin. Hits from this assay were tested in a plasma assay to assess inhibition of endogenous plasma autotaxin and subsequently tested for their ability to lower plasma LPA levels upon oral dosing of rats. The best compounds were then tested in animal models of musculoskeletal pain. Compound screening led to the identification of compounds with nanomolar potency for inhibition of autotaxin activity. Studies in rats demonstrated a good correlation between compound exposure levels and a decrease in LPA levels in plasma. The leading molecule (compound-1) resulted in a dose dependent decrease in joint pain in the mono-sodium iodoacetate (MIA) and meniscal tear models and a decrease in bone fracture pain in the osteotomy model in rats. We have identified and characterized a novel small molecule inhibitor of autotaxin and demonstrated its efficacy in animal models of musculoskeletal pain. The inhibitor has the potential to serve as an analgesic for human OA and bone fracture.

Shortening Scarf Osteotomy for Treatment of Hallux Rigidus Deformity

Purpose: To evaluate the effect of shortening scarf osteotomy on pain relief and range of motion (ROM) of the first metatarsophalangeal joint in hallux rigidus patients. Materials and Methods: Twenty-three cases of 19 patients who had been treated with shortening scarf osteotomy for the hallux rigidus between January 2007 and December 2013 were reviewed. The mean follow-up period was 21.4 months, and the mean age was 59.2 years. The first metatarsal bone was shortened until the ROM of the first metatarsophalangeal joint was greater than 80° or 40° of dorsiflexion. The length shortened by scarf osteotomy was measured. The authors also measured and compared the joint interval difference of the standing foot using an anteroposterior radiography. Moreover, the difference of ROM of the first metatarsophalangeal joint between the preoperative and final follow-up periods was also compared. The clinical results were evaluated and compared using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring system and visual analogue scale (VAS) score. Results: The mean shortening length was about 6.5 mm (range, 4∼9 mm). The joint space has been increased to 1.8 mm, and the ROM of the first metatarsophalangeal joint has also been increased to 18.4° after the operation. In three cases, the postoperative ROM has been decreased to less 10°. The AOFAS score has been improved from 41.7 (range, 32∼55) to 86.2 (range, 65∼95), and the VAS score was also decreased from 3.7 (range, 3∼5) to 1.3 (range, 0∼3). Two cases have shown no decrease in pain even after the operation. Conclusion: Shortening scarf osteotomy was found to decrease joint pain by decompressing the pressure of the first metatarsophalangeal joint. This osteotomy also helped improve the ROM of the first metatarsophalangeal joint. Shortening scarf osteotomy can be considered one of the effective methods for joint preservation.

Daily sesame oil supplement attenuates joint pain by inhibiting muscular oxidative stress in osteoarthritis rat model

Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague–Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose-dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model.

Extracorporeal shock-wave therapy reduces progression of knee osteoarthritis in rabbits by reducing nitric oxide level and chondrocyte apoptosis

The goal for treating osteoarthritis (OA) is finding ways to decrease joint pain and dysfunction and prevent and slow the cartilage degeneration. Extracorporeal shock-wave therapy (ESWT) has been found to improve motor dysfunction and ameliorate pain with OA in animals. However, few studies have found that it can prevent and slow joint degeneration in vivo. The aim of study was to investigate the effect of ESWT on OA in rabbit. A total of 30 male New Zealand white rabbits were divided into 3 groups: control, OA induced by anterior cruciate ligament transaction (ACLT), and ALCT plus ESWT. The animals were killed at 4 and 8 weeks. Nitric oxide (NO) level was measured in the synovial cavity of knee joints, and cartilage sections were graded macroscopically by a Mankin scoring system. Chondrocyte apoptosis was investigated by flow cytometry and the expression of active caspase 3 by indirect immunohistochemistry. ESWT significantly reduced the NO level in the synovial cavity of knee joints (P < 0.05) and chondrocyte apoptosis (P < 0.05) of rabbits with OA. ESWT treatment significantly decreased the severity of cartilage lesions at both times as compared to rabbits with OA alone (P < 0.05). ESWT reduced the progression of OA in rabbits. This effect may be related to decreased level of NO and is likely mediated by reduced chondrocyte apoptosis. ESWT may be a useful treatment for knee OA.

Avaliação do papel de opioides endógenos na analgesia do laser de baixa potência, 820 nm, em joelho de ratos Wistar

JUSTIFICATIVA E OBJETIVOS: A sensação de dor pode resultar em incapacidade, sendo associada à lesão estrutural. O laser de baixa potência mostra-se útil em terapias que objetivam a redução da dor articular e o reparo tecidual, mas ainda com algumas controvérsias. O objetivo deste estudo foi avaliar se a analgesia produzida pelo laser de baixa potência, 820 nm, sofre interferência pela aplicação de um inibidor de opioides endógenos. MÉTODO: Foram utilizados 24 ratos Wistar submetidos à hiperalgesia e divididos em quatro grupos: G1: não tratados; G2: tratados com laser 820 nm; G3: prévio a lesão, injeção de naloxona e não tratados; G4: naloxona e tratados com laser 820 nm. Para a produção de hiperalgesia foi administrado 100 µL de formalina a 5% no espaço articular tíbio-femoral direito. A avaliação da nocicepção ocorreu pelo tempo de elevação da pata (TEP), em cinco momentos, sendo AV1 (pré-lesão), AV2 (15 min/pós), AV3 (30 min/pós), AV4 (1 hora pós) e AV5 (2 horas pós). RESULTADOS: Todos os grupos apresentaram diferença significativa entre AV1 e AV2, mas, apenas G2 não apresentou diferença entre AV1 e AV3. Para os momentos seguintes não houve diferenças com relação à AV1. CONCLUSÃO: A analgesia oriunda do laser de baixa potência, 820 nm, sofre interferências com aplicação de naloxona.

아로마요법이 류마티스 관절염 환자의 통증과 염증반응에 미치는 효과

Purpose: The aim of the present study was to examine the effects of a 4-week aromatherapy on pain and inflammation in patients suffering from rheumatoid arthritis. Methods: A quasi-experimental study using a nonequivalent control group, pretest-posttest non-synchronized design was used. To analyze the data, descriptive statistics, Chi-square test, independent samples t-test, and Fisher's exact test were used. Results: After a 4-week aromatherapy, tender joint count (M=5.67 to 4.17), swollen joint count (M=4.13 to 2.54), and patient's assessment of pain (M=43.33 to 31.08) decreased significantly for the aromatherapy participants compared to the control group. But there was no significant difference between the groups in erythrocyte sedimentation rate. Conclusion: These findings suggest that aromatherapy could decrease joint pain, tenderness, and swelling in patients with rheumatoid arthritis, but some modifications in aromatherapy intervention and research method will be required to examine the effects of aromatherapy on inflammatory level in this population.

Fixed Orthodontic Therapy in Temporomandibular Disorder (TMD) Treatment: An Alternative to Intraoral Splint

This study evaluated the use of a fixed orthodontic appliance in treatment of temporomandibular disorder (TMD) compared to the use of an intra-oral splint. Fifty (50) adult patients, with confirmed anterior disk displacement with reduction in at least one temporomandibular joint (TMJ), were divided into three groups: 20 patients treated with AR splint (Group I); 20 patients treated with a fixed orthodontic appliance (Group II) and 10 patients who underwent no treatment (Control Group). Joint pain, joint noise, muscle pain, and subjective relief were evaluated monthly before the treatment began (T0) and for six months thereafter. Subjects in Group I and Group II displayed a significant decrease in joint pain (p<0.01) from T2 and in muscle pain from T1 (p<0.01) to T6. Subjects in Group I showed a higher decrease in the frequency of joint noise (p<0.05) from T1 to T6, compared with Group II. At T2 and T3, the patients in Group II reported a significantly lower discomfort level associated with the devices than subjects treated with the AR splint (p<0.05). However, at T5 and T6, this observation was inverted. The use of a fixed orthodontic appliance seems to be as efficacious as the use of an AR maxillary splint in the treatment of joint pain and muscle pain, but not in the treatment of joint noise. These results are valid, at least for the short-term clinical results (first six months of treatment). Clinical implications for long-term use are not clarified by these results.

Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol®

In a previous, double-blind, placebo-controlled study we evaluated the efficacy of a 3-month treatment with Pycnogenol® for 156 patients with osteoarthritis of the knee. Pycnogenol® significantly decreased joint pain and improved joint function as evaluated using the WOMAC score and walking performance of patients on a treadmill. In this study, we further investigated the anti-inflammatory and antioxidant activity of Pycnogenol® in a subset of the osteoarthritis patients presenting with elevated C-reactive protein (CRP) and plasma-free radicals. Elevated CRP levels have been suggested to be associated with disease progression in osteoarthritis. In our study, 29 subjects of the Pycnogenol® group and 26 patients in the placebo group showed CRP levels higher than 3 mg/l at baseline. Comparison of blood specimens drawn at baseline and after 3-month treatment showed that Pycnogenol® significantly decreased plasma free radicals to 70.1% of baseline values. Plasma CRP levels decreased from baseline 3.9 mg/l to 1.1 mg/l in the Pycnogenol® group whereas the control group had initial values of 3.9 mg/l which decreased to 3.6 mg/l. The CRP decrease in the Pycnogenol® was statistical significant as compared to the control group (P < 0.05). Fibrinogen levels were found to be lowered to 62.8% of initial values (P < 0.05) in response to Pycnogenol®. No significant changes for plasma free radicals, CRP and fibrinogen were found in the placebo-treated group. The decrease of systemic inflammatory markers suggests that Pycnogenol® may exert anti-inflammatory activity in osteoarthritic joints and patients did not present with other ailments or infections. The nature of the anti-inflammatory effects of Pycnogenol® with regard to CRP warrants further investigation.

Long term effects of intra-articular botulinum toxin a for refractory joint pain

The purpose of this case series review is to describe our 12 month clinical experience with intra-articular injections of Botulinum toxin Type A (BoNT/A) for refractory joint pain. Eleven patients with chronic arthritis who had failed treatment with oral and/or intra-articular medications and were not surgical candidates were referred to us for management of moderate to severe refractory joint pain in 15 joints. The use of BoNT/A to treat joint pain is a non-FDA approved "off label" treatment with potential side effects. After a detailed explanation of the joint injection procedure, signed informed consent was obtained for the procedure. Fifteen joints were injected with BoNT/A (Allergan, Inc): six lower extremity joints (3 knees, 3 ankles) with 25-50 units and nine shoulders with 50-100 units. Patients were followed for one year or longer. Maximum relief of pain was measured by comparing baseline pain on a numeric rating scale (0-10) to pain at the time of maximum relief (paired t-test). Maximum improvement in function was assessed using paired t-tests for improvement in active flexion and abduction for the shoulder joint, and by the time to perform sit to stand ten times (the timed stands test, TST) for the lower extremity joints. Two patients were female and nine were male, aged 42-82 years. Five had osteoarthritis (OA), five had rheumatoid arthritis (RA) and one had psoriatic arthritis. All patients were on analgesic and/or anti-inflammatory medications and all joints had previous intra-articular steroid or viscosupplement injections with inadequate or unsatisfactory benefit. A clinically and statistically significant improvement was noted after IA-BoNT/A injections. The mean maximum decrease in lower extremity joint pain was 55% (p =0.02) and the 36% (p =0.044) improvement in the Timed Stands Test was noted at four to ten weeks after injection. There was a 71% mean maximum reduction in shoulder pain severity from 8.2 +/- 1.1 to 2.4 +/- 1.9 (p <0.001). Active range of motion increased 67% in flexion (from 67.8 +/- 27.6 to 113.3 +/- 46.6 degrees, p =0.001) and 42% in abduction (from 50 +/- 18.5 degrees to 71.1 +/- 23.1 degrees p =0.01). No immediate or delayed adverse effects related to BoNT/A were noted after the injection. Duration of pain relief was variable and ranged from 3 to 12 months. Five joints were re-injected with IA-Bont/A and had a similar decrease in joint pain that lasted 3 to 12 months. This is the first report of the long term effects of intra-articular BoNT/A injections to treat chronic joint pain and the efficacy of repeated injections. Although this study was small, and uncontrolled the results suggest that IA-BoNT/A injections are an effective and safe treatment for chronic joint pain disorders.

Intra-articular and Muscle Symptoms and Subjective Relief During TMJ Internal Derangement Treatment with Maxillary Anterior Repositioning Splint or SVED and MORA Splints: A Comparison with Untreated Control Subjects

Discomfort associated with wearing an intraoral splint represents a problem in the management of temporomandibular joint (TMJ) internal derangement. This study evaluated whether the use of a mandibular splint during the day and a maxillary splint at night could be more comfortable and therefore as efficacious in internal derangement treatment as a maxillary splint (AR splint). Fifty (50) patients (average age 28.8; range 14-63) with confirmed internal derangement in at least one TMJ were divided into three groups: 20 patients treated with AR splint (Group I); 20 patients treated with a SVED (Sagittal Vertical Extrusion Device) and a MORA (Mandibular Anterior Repositioning Splint) (Group II); and 10 patients who underwent no treatment (Control Group). Joint noise, pain intensity and its character (as constant or chewing/biting pain), muscular pain, and subjective relief were evaluated monthly before treatment began (T0) and for six months thereafter. The following results were found: 1. Subjects in Group I and Group II displayed a significant decrease in joint pain (p<0.001), constant pain (p<0.001), chewing/biting pain (p<0.001), joint noise and muscle pain from the beginning through the sixth month follow-ups; 2. At T1 and T2, subjects in Group II reported significantly lower discomfort associated with the devices than subjects in Group I. The use of two splints seems to be as efficacious as the use of an AR maxillary splint; however an AR splint is considered more comfortable by patients, especially during the first months of therapy.

Comparison of glucosamine‐containing dietary supplements on knee osteoarthritis symptoms

A preliminary, randomized, double-blind, placebo-controlled, parallel-group clinical study compared efficacy and tolerability of dietary supplements on 107 total subjects with mild to moderate osteoarthritis (OA) of the knee over 8 weeks. Average age was 57 ± 10 years. 18 subjects per group took either placebo (maltodextrin) (Group 1), glucosamine HCl (1500 mg) (Group 2), glucosamine HCl (1500 mg) & chondroitin sulfate (1200 mg) (Group 3), glucosamine HCl (1500 mg) & chondroitin (1200 mg) & sodium hyaluronate (3.3 mg) (Group 4), glucosamine HCl (1500 mg) & a proprietary herbal extract (250 mg) & sodium hyaluronate (3.3 mg) (Group 5), or an experimental formula (Group 6). Acetaminophen was used as rescue medication. WOMAC, SF-36v2, Brief Pain Inventory (BPI), and Pain Relief Diary (PRD) outcomes were measured at 0, 1, 2, 4, and 8 weeks. Comparisons of Intention-To-Treat data across all groups were performed using one-way factorial ANOVA. There were no significant differences among groups at baseline. Incidence of side effects among groups was not different. All of the groups reported improvements in the subjects’ perceptions of their condition (pain, quality of life, etc.). All groups showed similar efficacy, except for the following: Group 3 was less effective in relieving pain than the other groups; and Group 5 was rated best by the subjects in decreasing joint pain and muscle aches, and showed the greatest amount of rapid-onset improvement in physical functioning. Supported by Schiff Nutrition International, Inc.

P.358 Autotaxin and lysophosphatidic acid in the blood in patients of viral hepatitis

Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production in vivo and determine its efficacy in animal models of musculoskeletal pain.Compound libraries were screened using an LPC coupled enzyme assay that measures the amount of choline released from LPC by the action of autotaxin. Hits from this assay were tested in a plasma assay to assess inhibition of endogenous plasma autotaxin and subsequently tested for their ability to lower plasma LPA levels upon oral dosing of rats. The best compounds were then tested in animal models of musculoskeletal pain.Compound screening led to the identification of compounds with nanomolar potency for inhibition of autotaxin activity. Studies in rats demonstrated a good correlation between compound exposure levels and a decrease in LPA levels in plasma. The leading molecule (compound-1) resulted in a dose dependent decrease in joint pain in the mono-sodium iodoacetate (MIA) and meniscal tear models and a decrease in bone fracture pain in the osteotomy model in rats.We have identified and characterized a novel small molecule inhibitor of autotaxin and demonstrated its efficacy in animal models of musculoskeletal pain. The inhibitor has the potential to serve as an analgesic for human OA and bone fracture.

Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial

Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of depression associated with the condition. 618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with with the identifier NCT00111449. 47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0.0001; difference 42%, 95% CI 36-48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5.0 vs 1.9; p<0.0001, difference 3.0, 95% CI 1.6-4.5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain. Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.

Alflutop in osteoarthritis therapy

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