Preoperative intra-articular steroid injections within 3 months increase the risk of periprosthetic joint infection in total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Albeit with no disease-modifying effects, intra-articular steroid injections (IASIs) are still widely used to relieve symptoms of knee osteoarthritis. Previous literature has reported conflicting results regarding the safety of IASI in terms of periprosthetic joint infection (PJI) in total knee arthroplasty (TKA). This study tried to determine whether preoperative IASIs increased the risk of PJI, with different time intervals between the injections and surgery. METHODS: A computerized search of MEDLINE, EMBASE, and Cochrane Library was conducted for studies published before October 2022, which investigated the PJI rates of patients who received IASIs before TKA and patients who did not. The primary outcome was the association between preoperative IASI and PJI in TKA. The time point from which IASIs could be applied without risking PJI was also assessed. RESULTS: Fourteen studies, with 113,032 patients in the IASI group and 256,987 patients in the control group, were included. The pooled odds ratio of PJI was 1.13 (95% confidence interval [CI] 1.00-1.27, p = 0.05), indicating no increased risk of PJI. With the time interval < 6 months, the pooled odds ratio was 1.19 (95% CI 0.99-1.43, p = 0.06). However, with the time interval < 3 months, the pooled odds ratio was 1.26 (95% CI 1.06-1.50, p < 0.01). CONCLUSION: IASI is not a safe procedure for patients who are expected to undergo TKA. The time interval between the injections and surgery was an important factor in assessing the safety of IASI. Preoperative injections that were applied within 3 months increased the risk of PJI in TKA.

Does intra-articular injection of tenoxicam after arthrocentesis heal outcomes of temporomandibular joint osteoarthritis? A randomized clinical trial.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease and manifests itself with pain and limitation of movement in the jaws. Arthrocentesis alone or in combination with intraarticular injections is one of the most commonly used treatment methods in these patients. The aim of the study is to examine the effectiveness of arthrocentesis plus tenoxicam injection and to compare it with arthrocentesis alone in patients with TMJ-OA. METHODS: Thirty patients with TMJ-OA who were treated randomly with either arthrocentesis plus tenoxicam injection (TX group) or arthrocentesis alone (control group) were examined. Maximum mouth opening (MMO), visual analog scale (VAS) pain values, and joint sounds were the outcome variables, which were evaluated at pre-treatment and at 1, 4, 12, and 24 weeks after treatment. Statistical significance was set at p < 0.05. RESULTS: The gender distribution and mean age were not significantly different between the two groups. Pain values (p < 0.001), MMO (p < 0.001), and joint sounds (p < 0.001) improved significantly in both groups. However, there was no significant difference between the groups in terms of outcome variables [pain (p = 0.085), MMO (p = 0.174), joint sounds (p = 0.131)]. CONCLUSIONS: Arthrocentesis plus tenoxicam injection showed no better outcomes in terms of MMO, pain, and joint sounds compared with arthrocentesis alone in patients with TMJ-OA. TRIAL REGISTRATION: Injection of Tenoxicam Versus Arthrocentesis Alone in the Treatment of Temporomandibular Joint Osteoarthritis, NCT05497570. Registered 11 May 2022. Retrospectively registered, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000CD7A&selectaction=Edit&uid=U0006FC4&ts=6&cx=f3anuq.

The efficacy of intra-articular triamcinolone acetonide 10 mg vs. 40 mg in patients with knee osteoarthritis: a non-inferiority, randomized, controlled, double-blind, multicenter study.

BACKGROUND: Intra-articular (IA) corticosteroid injection is recommended in refractory knee osteoarthritis patients. However, 40-mg of triamcinolone IA every 3 months for 2 years reduces cartilage volume as compared to saline IA. OBJECTIVE: To determine the non-inferiority of 10-mg versus 40-mg of triamcinolone acetonide (TA) for treatment of pain in symptomatic knee osteoarthritis at week 12. METHODS: This was a double-blind, randomized, controlled trial conducted in 84 symptomatic knee osteoarthritis patients. The 10-mg or 40-mg of TA were 1:1 randomized and injected to the affected knees. The primary outcome was the 12-week difference from baseline in pain VAS, with a pre-specified lower margin for non-inferiority of 10 mm. The measuring instruments used were: Visual analog scale (VAS: 0-10), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Group 5 Dimensions (EQ5D), Knee Injuries and Osteoarthritis Outcome Score (KOOS) questionnaire, chair standing test and 20-m walking time at baseline, at week 4, and week 12 after randomization. Adverse events were recorded. RESULTS: Baseline characteristics were similar between two groups. The mean differences of pain VAS (95% confidence interval: CI) between the two groups at baseline and week 12 were 0.8 (-0.8, 2.4) with p of 0.002 for non-inferiority. There were no differences in pain reduction and quality of life improvement between 10-mg and 40-mg groups. The mean differences (95%CI) of WOMAC, KOOS pain, EQ5D and KOOS quality of life between baseline and week 12 were 0.4 (-1.1, 1.9). -8.7 (-21.3, 3.9), 1.3(-7.1, 9.6) and 1.8 (-11.5, 15.0), respectively. There were significant improvements in pain and quality of life between baseline and week 12 in both groups. CONCLUSION: The 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. Both 10 mg and 40 mg of TA significantly improved pain and quality of life in patients with symptomatic knee OA. TRIAL REGISTRATION: TCTR, I TCTR20210224002. Retrospectively registered 24 February 2021, http://www.thaiclinicaltrials.org/show/TCTR20210224002.

Efficacy of high-volume vs very low volume corticosteroid subacromial injection in subacromial impingement syndrome: a randomized controlled trial.

Subacromial corticosteroid injections (SCI) treat shoulder pain from subacromial impingement syndrome (SIS). However, a high-volume corticosteroid injection (HVCI) increases the incidence of local and general complications from lidocaine. This study aimed to compare the results of functional and clinical outcomes between the very low-volume corticosteroid injection (VLVCI) and HVCI including to WORC (Western Ontario Rotator Cuff Index), VAS (Visual Analog Scale), DASH (The disabilities of the arm, shoulder, and hand) and ROM (Range of Motion). A total of 64 patients presenting with SIS were evaluated in two SCI volume in a randomization-controlled trial study. The VAS for pain pre-injection and post-injection at 15 min, was from 5.34 ± 2.44 at before injection to 2.44 ± 1.58 at post injection 15 min in the HVCI group (P < 0.001) and from 5.19 ± 2.33 to 2.84 ± 1.49 in VLVCI group (P < 0.001). Not significant differences at mean difference VAS post-injection 15 min VAS (P = 0.324) and Percentage difference VAS pre-injection and post-injection (P = 0.24). All follow-up timing, there were no significant differences in WORC, DASH and ROM between two groups (P > 0.05). The results revealed the VLVCI is non-inferior to HVCI both of functional outcomes and VAS.

Efficacy of Phrenic Nerve Block and Suprascapular Nerve Block in Amelioration of Ipsilateral Shoulder Pain after Thoracic Surgery: A Systematic Review and Network Meta-Analysis.

Background and Objectives: Ipsilateral shoulder pain (ISP) is a common complication after thoracic surgery. Severe ISP can cause ineffective breathing and impair shoulder mobilization. Both phrenic nerve block (PNB) and suprascapular nerve block (SNB) are anesthetic interventions; however, it remains unclear which intervention is most effective. The purpose of this study was to compare the efficacy and safety of PNB and SNB for the prevention and reduction of the severity of ISP following thoracotomy or video-assisted thoracoscopic surgery. Materials and methods: Studies published in PubMed, Embase, Scopus, Web of Science, Ovid Medline, Google Scholar and the Cochrane Library without language restriction were reviewed from the publication's inception through 30 September 2022. Randomized controlled trials evaluating the comparative efficacy of PNB and SNB on ISP management were selected. A network meta-analysis was applied to estimate pooled risk ratios (RRs) and weighted mean difference (WMD) with 95% confidence intervals (CIs). Results: Of 381 records screened, eight studies were eligible. PNB was shown to significantly lower the risk of ISP during the 24 h period after surgery compared to placebo (RR 0.44, 95% CI 0.34 to 0.58) and SNB (RR 0.43, 95% CI 0.29 to 0.64). PNB significantly reduced the severity of ISP during the 24 h period after thoracic surgery (WMD -1.75, 95% CI -3.47 to -0.04), but these effects of PNB were not statistically significantly different from SNB. When compared to placebo, SNB did not significantly reduce the incidence or severity of ISP during the 24 h period after surgery. Conclusion: This study suggests that PNB ranks first for prevention and reduction of ISP severity during the first 24 h after thoracic surgery. SNB was considered the worst intervention for ISP management. No evidence indicated that PNB was associated with a significant impairment of postoperative ventilatory status.

Evaluation of the efficiency of hyaluronic acid, PRP and I-PRF intra-articular injections in the treatment of internal derangement of the temporomandibular joint: A prospective study.

This study aimed to evaluate the clinical effects of hyaluronic acid (HA), platelet-rich plasma (PRP), and platelet-rich fibrin (I-PRF) injections in the internal derangement of the temporomandibular joint. Adult patients who had failed to respond to nonsurgical treatment were were included in the study. The patients were divided into three treatment groups according to the given substance: 1) HA administration three times in a row on a weekly basis, 2) a single dose of PRP, or 3) a single dose of I-PRF. Clinical assessment was performed preoperatively and 6 and 12 months after the treatment, including maximal mouth opening (MMO) and pain level (Visual Analog Scale). Low and high molecular weight (HAL, HAH) hyaluronic acid forms were also compared. 68 adult patients, with a total of 109 joints were included in the study. The mean age was 53 ± 16 years. The statistical analysis showed a significant improvement in MMO in the HA group (p < 0.01). The pain level significantly decreased in all treatment groups (pHA,PRP,I-PRF<0.01). Comparing HAL and HAH forms, no significant difference was found in the evaluation of MMO and VAS values. Within the limitations of the study it seems that due to the similar effects of HA and the autologous blood substances, the platelet concentrates should be preferred in the intra-articular treatment in order to reduce the risk of possible adverse effects.

Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

Comparison of intra-articular injection of ArtiAid®-Mini with Ostenil®-Mini for trapeziometacarpal osteoarthritis: A double-blind, prospective, randomized, non-inferiority trial.

OBJECTIVES: This study aims to compare the effectiveness and safety of intra-articular hyaluronic acid (HA) injections of ArtiAid®-Mini (AAM) and Ostenil®-Mini (OM) for the treatment of trapeziometacarpal joint osteoarthritis. PATIENTS AND METHODS: Between February 2018 and April 2020, this 24-week, double-blind, prospective, randomized, non-inferiority trial included a total of 17 patients (8 males, 9 females; mean age: 60.3±9.5 years; range, 42 to 76 years) who were treated with either intra-articular AAM (n=8) or OM (n=9). The primary outcome was pain according to a change in Visual Analog Scale (VAS) at 12 weeks after the last injection. The secondary outcomes included the change of VAS at Weeks 2, 4, and 24 after the injection, satisfaction, range of motion (ROM) of trapeziometacarpal joint, pinch strength, grip strength, and adverse events at Weeks 2, 4, 12, and 24 after the injection. RESULTS: Eight patients with AAM and eight patients with OM completed the follow-up. No significant differences in primary and secondary outcomes were observed between the two groups at baseline and each time point (p>0.05). The intra-group differences were significant in each time point. CONCLUSION: The intra-articular injection of either AAM or OM is effective and safe for patients with trapeziometacarpal osteoarthritis up to 24 weeks.

Comparison of the efficacy of intra-articular injections of hyaluronic acid and lactoferrin in mono-iodoacetate-induced temporomandibular joint osteoarthritis: A histomorphometric, immunohistochemistry, and micro-computed tomography analysis.

OBJECTIVES: This study aims to evaluate the efficacy of high-molecular-weight hyaluronic acid (HMWHA) and lactoferrin (LF) injections on temporomandibular joint (TMJ) cartilage and subchondral bone in mono-iodoacetate (MIA)-induced temporomandibular joint osteoarthritis model in rats. MATERIALS AND METHODS: In this in vivo study, a total of 24 rats were divided into three groups as follows: saline group (Group 1), HMWHA group (Group 2), and LF group (Group 3) including eight rats in each group. The intra-articular injections were administered once a week for three weeks after osteoarthritis was induced. All animals were euthanized 28 days after induction of osteoarthritis, and TMJs were harvested for histomorphometric, immunohistochemical, and micro-computed tomography (CT) analysis. RESULTS: There was no significant difference between the HMWHA and LF groups in terms of the histomorphometric and immunohistochemical analysis results (p>0.05). According to the micro-CT analysis, the LF group had the highest mean bone volume fraction (74.9±0.5) and trabecular thickness (0.122±0.002), while the saline group had the lowest mean values (55.0±0.3 and 0.071±0.002, respectively) (p<0.001). There was no significant difference between the HMWHA and LF groups according to the micro-CT analysis (p>0.05). Both groups had better healing effects than the saline group in all analyses. CONCLUSION: Lactoferrin has a healing effect at least as much as HMWHA in MIA-induced TMJ osteoarthritis. We suggest that LF may be evaluated in future clinical studies as a promising agent in the treatment of osteoarthritis.

Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. METHODS: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). DISCUSSION: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk-benefit profile of this treatment in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.

Cost-utility analysis and net monetary benefit of Platelet Rich Plasma (PRP), intra-articular injections in compared to Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone in knee osteoarthritis in Iran.

PURPOSE: To evaluate the cost-effectiveness of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone as effective treatment approaches in knee osteoarthritis management from Iran Health care perspective. METHODS: A decision tree model was conducted to assess the cost-effectiveness of four common intra-articular treatment approaches in patients with mild and moderate knee osteoarthritis. The data on clinical effectiveness was obtained from a randomized controlled trial (RCT) conducted in Iran and used to estimate utility values. The direct medical costs were estimated according to tariffs for public medical centers and hospitals, approved by the Iran Ministry of Health and Medical Education in 2021. The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NMB) were used to evaluate the cost-utility analysis. Deterministic and probabilistic sensitivity analyses are performed to investigate the robustness of the results and account for the different sources of uncertainty. RESULTS: In this study, HA intra-articular injection-related costs ($581.67/patient) were defined as the highest cost, followed by PRGF ($328.10/patient), PRP (318.58/patient), and Ozone (103.20/patient). According to the utility value, PRP and PRGF (0.68) have the same and the most utility among Intra-articular injections in knee osteoarthritis management. However, the PRP injection method was identified as the most cost-effective intervention due to its high NMB and ICER estimates. Based on the Monte Carlo Simulation, PR intervention, compared to other ones, was introduced as the dominant strategy regarding knee OA management, with a WTP of $10,000 for 100% of cases. CONCLUSION: The study result demonstrated that intra-articular injection of PRP, compare to other injections, is a cost-effective treatment option for patients with mild and moderate knee osteoarthritis. In addition, intra-articular injection of PRP was identified as the best injection, with the highest level of net monetary benefit, for knee OA management.

Restoring Study PRGF: a randomized clinical trial on plasma rich in growth factors for knee osteoarthritis.

BACKGROUND: A randomized clinical trial assessing plasma rich in growth factors (PRGF) versus hyaluronic acid for knee osteoarthritis was published in 2012 (sponsor trial ID BTI-01-EC/07/ART). Evidence of misreporting was discovered following access to unpublished materials. In accordance with the principles of the Restoring Invisible and Abandoned Trials (RIAT) initiative, we sought to re-analyse Study PRGF based on the unpublished trial materials. METHODS: Reanalysis was made possible primarily based on two unpublished study documents (original trial protocol and final report) obtained from the authors of the original publication. A call to action, calling on the authors to correct the original publication, was publicly issued. The involved ethics committee was repeatedly approached and extensive discussion with the authors ensued. After no agreement to correct the paper was reached, we embarked on this restoration. Reanalysis was focused on providing updated analyses for efficacy and safety. RESULTS: The efficacy of PRGF was not statistically different from hyaluronic acid for any prespecified primary or secondary efficacy outcomes. For the primary endpoint, the percent of patients on PRGF compared to hyaluronic acid with a decrease >40% in WOMAC pain subscale score was 5.4% higher; 95% confidence interval (CI) -10.4% to 21.3%; p = 0.505. This differs from the original publication that reported a non-prespecified primary endpoint (decrease >50% in WOMAC pain subscale score) which was 14.1% higher; 95% CI 0.5 to 27.6%; p=0.044. Furthermore, in contrast to the article statement that all the adverse events disappeared in 48 h, at least two patients in the hyaluronic arm and five patients in the PRGF arm reported persistent adverse events. Inadequate disclosure of conflicts of interest in the original publication was also noted. CONCLUSIONS: This reanalysis of Study PRGF found no clinically or statistically significant benefit from PRGF compared to hyaluronic acid. The restoration of Study PRGF shows the urgency of important changes to trial reporting and oversight practices. In the future, timely access to all clinical trial documents is needed to minimize the risk of reporting bias. Similarly, ethics committees should be ready to intervene whenever a case of potential misconduct arises. TRIAL REGISTRATION: This is a RIAT project, whose original trial was approved and registered on 19 December 2007 by the Ethics Committee of the Basque Country, Spain, as BTI-01-EC/07/ART.

Intra-Articular Injection of Botulinum Toxin for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached "Good quality" standard, three were ranked as "Fair", and the rest were considered "Poor". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.

Comparison of Outcomes of Two Different Corticosteroid Injection Approaches for Primary Frozen Shoulder: A Randomized Controlled Study.

OBJECTIVE: Corticosteroid injection is a common treatment for primary frozen shoulder, but controversy remains regarding whether different injection approaches to the glenohumeral joint have similar clinical benefits. DESIGN: Randomized controlled clinical trial. PATIENTS: A total of 60 patients with primary frozen shoulder were divided randomly into either anterior or posterior approach groups. METHODS: Both groups received a 5-mL drug injection, including 1 mL 40 mg/mL triamcinolone acetonide and 4 mL 2% lidocaine. Follow-up time-points were 4, 8 and 12 weeks post-injection. Outcome measures included visual analogue scale score, Constant-Murley score, and passive range of motion of the shoulder joint. RESULTS: All outcome measures improved over the follow-up period compared with those of previous follow-up time-points within the groups. The primary finding was that the visual analogue scale score in the anterior group was better than that in the posterior group at each follow-up time-point (all p < 0.05). In addition, improvement in function score and external rotation was faster and significant in the anterior group in the early stages (p = 0.02). CONCLUSION: The anterior approach achieves more satisfactory results in pain control and offers better recovery of functional activity than posterior approach in the early period for primary frozen shoulder.

Comparison of chemical-induced temporomandibular osteoarthritis rat models (monosodium iodoacetate versus collagenase type II) for the study of prolonged drug delivery systems.

OBJECTIVE: To compare two agents that can induce a rat model of temporomandibular joint osteoarthritis (TMJOA) by chemical induction: monosodium iodoacetate (MIA) and collagenase type 2 (Col-2). We wished to ascertain the best agent for assessing drug-delivery systems (DDSs). METHOD: Male Wistar rats underwent intra-articular injection with MIA or Col-2. They were manipulated for 30 days. The head withdrawal threshold (HWT), immunohistological assessment, and positron emission tomography (PET) were used to evaluate the relevance of our models. RESULTS: For both the MIA and Col-2 groups, pain persisted for 30 days after injection. Change in the HWT showed that Col-2 elicited a strong action initially that decreased progressively. MIA had a constant action upon pain behavior. Histology of TMJ tissue from both groups showed progressive degradation of TMJ components. CONCLUSIONS: MIA and Col-2 induced orofacial pain by their local chemical action on TMJs. However, based on a prolonged and greater sustained effect on the pain threshold, persistent histological changes, and imaging results, MIA appeared to be more suitable for creation of a rat model of TMJOA for the study of DDSs.

Can pre-operative intraarticular injection predict pain relief after total hip arthroplasty?

BACKGROUND: To study if pain relief after injection and arthroplasty correlate. METHODS: A retrospective cohort study included consecutive patients (n = 88; median age 64 (interquartile range (IQR) 22) years, 49 (56%) females) that received fluoroscopic-guided intra-articular hip injection with contrast agent, anaesthetic (diagnostic), and corticosteroid (therapeutic) before implantation of primary total hip arthroplasty. Pain scores were assessed pre-injection, post-injection after 15 min (diagnostic phase) at first clinical follow up (therapeutic phase; median 2 (IQR 2) months), and postoperatively (last follow up (median 15 (IQR 5) months)). Responders had reduction in pain score ≥ 20 (numeric rating scale 0-100) points. The primary outcome was the same (or inverse) response to injection and arthroplasty. RESULTS: The median pain scores were higher pre-injection (68 (IQR 30) points) compared to the diagnostic phase (18 (IQR 40) points; p < 0.001), therapeutic phase (50 (IQR 40) points; p < 0.001), and post-operatively (2 (IQR 15) points; p < 0.001). On the one hand, 69 (78%) cases had the same response in the diagnostic phase and post-operatively (rho = 0.58; p < 0.001; sensitivity 83%); on the other hand 32 (36%) cases had the same response in the therapeutic phase and post-operatively (rho = 0.25; p < 0.001; sensitivity 33%). Furthermore, 57% and 91% of patients had an even better response post-operatively than in the diagnostic and therapeutic phases. CONCLUSIONS: Pre-operative intraarticular injection can predict pain relief after primary total hip arthroplasty. A positive response to hip arthroplasty may be better predicted by the response to local anaesthetic (diagnostic phase) than corticosteroids. Most patients (91%) with osteoarthritis may expect better pain relief after arthroplasty compared to the therapeutic phase after injection.

Pain Intensity and Trajectory Following Intra-Articular Injection of Mono-Iodoacetate in Experimental Osteoarthritis: A Meta-Analysis of In Vivo Studies.

OBJECTIVE: Although most frequently used in experimental osteoarthritis (OA) pain induction, intra-articular mono-iodoacetate (MIA) injection lacks concluded references for dose selection and timing of intervention. Herein, we aimed to compare the pain intensity of rats induced by different doses of MIA and explored the trajectory of pain. DESIGN: PubMed, Embase, and Web of Science were searched up to June 2021 for literatures involving MIA experiments investigating OA pain. Pain intensity was measured based on weightbearing distribution (WBD) and paw withdrawal thresholds (PWT), and the pain trajectory was constructed by evaluating pain intensity at a series of time points after MIA injection. A conventional meta-analysis was conducted. RESULTS: A total of 140 studies were included. Compared with saline, MIA injections caused significantly higher pain intensity for WBD and PWT. Dose-response relationships between different doses of MIA and pain intensity were observed (P-for-trend<0.05). A pronounced increase in pain occurred from day 0 to day 7, but the uptrend ceased between day 7 and day 14, after which the pain intensity continued to rise and reached the maximum by day 28. CONCLUSIONS: Pain intensity after intra-articular MIA injection increased in a dose-dependent manner and the pain trajectory manifested a specific pattern consistent with the pathological mechanisms of MIA-induced pain, providing possible clues for proper dose selection and timing of specific OA pain interventions.