Osteoarthritis Pain Research Articles

THU471 Resolution Of Elevated Alkaline Phosphatase After Joint Replacement In Severe Osteoarthritis

Abstract Disclosure: J. Rakholiya: None. S. Nagaraj: None. P. Sharma: None. Introduction: Alkaline phosphatase (ALP) elevation is commonly seen in hepatobiliary disorders. Conditions of high turnover such as healing fractures, hyperparathyroidism, Pagets’ disease of the bone, also lead to ALP elevation (1). Osteoarthritis (OA), characterised by degeneration of articular cartilage, joint space narrowing, and osteophyte formation, rarely causes ALP elevation. We present a case of ALP elevation that resolved after the arthritic joint was replaced. Case Presentation: A 60-year-old female with history of bilateral knee OA presented to the endocrinology clinic due to elevated ALP for over a year. She reported chronic fatigue, sleep disturbance, dry skin, hair loss, inability to lose weight and anxiety. ALP level at presentation was 165 U/L. An extensive work-up showed unremarkable serum and ionized calcium, serum phosphorus, parathyroid hormone, vitamin D 25-OH, calcitriol, 24-hour urine calcium, serum protein electrophoresis, and 24-hour urine protein electrophoresis. Dual x-ray absorptiometry (DXA) scan was normal with Fracture risk assessment tool (FRAX) score 5.9% for major osteoporotic fracture and 0.2% for hip fracture. Patient underwent total left knee arthroplasty following which ALP improved from 165 U/L to 135 U/L within 9 weeks of the procedure. Five months later, ALP was elevated (164 U/L) again. She then underwent right knee arthroplasty and ALP dropped to normal level (114 U/L) within 1 week post-surgery. Discussion: We report the rare phenomenon of ALP elevation in severe OA, that resolved after joint replacement. OA is characterised by inflammation mediated cartilage destruction, subchondral bone change, osteophyte formation, and alterations of ligaments and meniscuses. Bone change in severe OA is associated with increased synovial fluid ALP level. However, there is a paucity of literature studying the association of ALP with OA. A cross-sectional study of 3060 patients demonstrated higher serum ALP with symptomatic knee OA. Another study showed higher ALP levels with increased joint stiffness. The ALP elevation was attributed to low grade inflammation causing an inflammatory response in chondrocytes, and osteoarthritic pain. There is a need for more studies to evaluate the utility of serum ALP as a biomarker for severe OA. Presentation: Thursday, June 15, 2023

SAT295 Metabolic And Endocrine Risks In Association With The Use Of Intraarticular Glucocorticoid Injections: A Retrospective Study

Abstract Disclosure: E. Rabiei-Flori: None. Y. Yin: None. F. Hasan: None. Introduction: The use of intraarticular glucocorticoid injections (IGCI) to alleviate chronic pain from degenerative joint disease (DJD) is very common and the frequency of their use is probably underestimated. In our clinical experience the harmful metabolic effects of the frequent IGCI use are concerning, yet are not well studied. It is well-known that chronic exposure to systemic glucocorticoids is the most common cause of Cushing’s syndrome; i.e., iatrogenic Cushing’s (IC). There are, however, limited data assessing the link between IGCI use and IC. Methods: In this retrospective study we compare the outcomes in two large populations, both of which had received intraarticular injections to alleviate DJD pain. The first population received IGCI, while the second (comparison) population received a non-steroid, hyaluronic acid injection (IAHA). We hypothesize that, compared to the use of IAHA, the use of IGCI is associated with worse metabolic and endocrine outcomes, such as higher frequencies of diabetes, insulin requirement, obesity, hypertension, osteoporosis, and vertebral compression fractures. We included patients aged 18-90 years who received ≥1 IAHA dose versus ≥ 5 IGCI to a major joint (hip, knee, or shoulder) between 1/1/2017-9/30/2021. Results: During the study period 34,600 subjects received at least one of the two treatments (30,273 received IGCI vs 4327 who received IAHA; ratio of IGCI to IAHA population ≈ 7). Among the IGCI population 2421 (8%) received ≥ 5 IGCI injections. Comparisons are provided for this subset vs. IAHA. At baseline, mean age in the IGCI vs IAHA groups were 66.3 (±11.5) and 63.8 (±11.8) years, respectively. The use of IGCI was 2 folds higher and the use of IAHA was 1.5 folds higher in females than males. Most patients were White (88.6% and 90% in the IGCI and IAHA groups, respectively). There was no difference in BMI between the groups at baseline (both 32.7 ± 7). Compared to the IAHA population, those who received ≥ 5 IGCI had significantly higher frequency of incident diabetes (42.1% vs. 35.3%, p 0.0006), requiring insulin therapy for diabetes (14.8% vs 12.6%, p=0.02), hypertension (55.4% vs. 43.6%, p <0.001), osteopenia (7.9% vs 5.7%, p=0.001), osteoporosis (8.8% vs 4.9%, p<0.0001), vertebral compression fracture (2.1% vs. 1.3%, p=0.04), depression (14.3% vs. 9.5%, p<0.001), cataract (3.6% vs. 2 %, p=0.0008), emergency room visit (48.8% vs 43.2%, p < 0.0001), ER visit for hypertension (3.4% vs 2.3%, p=0.02) and hospitalization for any reason (32.6% vs 27%, p<0.0001). Furthermore, the IGCI population had significantly lower lumbar spine BMD on DXA scan (0.98 vs 1.04 g/cm3, p=0.02). In contrast, the prevalence of obesity or severe obesity was not different between the two populations. Conclusion: compared to IAHA, the use of IGCI is associated with increased frequency of endocrine and metabolic risks that are observed in iatrogenic Cushing’s syndrome. Presentation: Saturday, June 17, 2023

Demographic predictors of central sensitization in patients of knee osteoarthritis

Context: Evidence suggests that central sensitization (CS) may contribute to pain in osteoarthritis (OA) knee patients, which cannot be treated by locally directed treatment strategies. Aims: The aim of this study was to examine differences in demographic profile of patients with and without central sensitization in osteoarthritis knee. Settings and Design: Observational cross-sectional study at tertiary care hospital. Materials and Methods: The study was conducted in the Department of Physical Medicine and Rehabilitation, VMMC and Safdarjung Hospital in 345 OA knee patients. Demographic profiles including age, gender, education, occupations, type of family, marital and socioeconomic status and central sensitization were assessed. The association between CS and various demographic parameters was investigated. Statistical Analysis Used: Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, version 21.0. For statistical significance, P value of less than 0.05 was considered statistically significant. Results: Ninety out of 345 (26%) of study subjects had CS; out of which 96% were females. Younger homemaker and those with unskilled/semiskilled type of job had higher chances of having CS in comparison with those with skilled and professional job (P < .001). Conclusions: Elicitation of specific demographic factors that can predict CS in people with knee OA may help in early identification and management of CS in OA knee patients.

Effect of acupuncture duration in patients with knee osteoarthritis: A secondary analysis of a multi-center randomized controlled trial: 治疗时长对针刺治疗膝骨关节炎疗效的影响:一项多中心随机对照试验的二次分析

ObjectiveTo explore the influence of acupuncture duration on the effect of acupuncute for patients with knee osteoarthritis (KOA). MethodsThis secondary analysis was conducted based on the data of a randomized controlled trial about acupuncture on KOA. A total of 480 patients were recruited at nine centers. Only data from the manual acupuncture (MA) group and electroacupuncture (EA) group were included in this secondary analysis. The needles were retained for 30-min each time and treatment was given three times a week for 8 weeks. The follow-up visit lasted until week 26. Outcomes were numerical rating scale (NRS) on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function and the response rate. ResultsThe NRS and WOMAC function at week 8 were lower than those at week 4 (P<0.05), and were no significant difference compared with those at week 26 in MA and EA groups (P>0.05). Greater changes were observed in NRS and WOMAC function during 0–4 weeks compared with those during 4–8 weeks (P<0.05) in both groups. The response rate at week 8 was higher than it at week 4 (P<0.05), and was no significant difference compared with it at week 26 (P>0.05) in both groups. Association was found between BMI and changes of NRS (P<0.05), but not between BMI and WOMAC function (P>0.05) in MA group, while no asscoaition was found between BMI and NRS or WOMAC function in EA group (P>0.05). There was no association found between other factors and NRS or WOMAC function in both groups (P>0.05). ConclusionFor KOA patients, 8-week acupuncture was more effective than 4-week acupuncture in relieving pain and improving joint function, but growth rate of the effect slowed down with increasing duration of intervention. It was uncertain whether the long-term effect of 8-week acupuncture was better than that of 4-week acupuncture. Further studies are required to further determine the effect of duration of intervention.

Effect of acupuncture duration in patients with knee osteoarthritis: A secondary analysis of a multi-center randomized controlled trial 治疗时长对针刺治疗膝骨关节炎疗效的影响:一项多中心随机对照试验的二次分析

ObjectiveTo explore the influence of acupuncture duration on the effect of acupuncute for patients with knee osteoarthritis (KOA). MethodsThis secondary analysis was conducted based on the data of a randomized controlled trial about acupuncture on KOA. A total of 480 patients were recruited at nine centers. Only data from the manual acupuncture (MA) group and electroacupuncture (EA) group were included in this secondary analysis. The needles were retained for 30-min each time and treatment was given three times a week for 8 weeks. The follow-up visit lasted until week 26. Outcomes were numerical rating scale (NRS) on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function and the response rate. ResultsThe NRS and WOMAC function at week 8 were lower than those at week 4 (P<0.05), and were no significant difference compared with those at week 26 in MA and EA groups (P>0.05). Greater changes were observed in NRS and WOMAC function during 0-4 weeks compared with those during 4-8 weeks (P<0.05) in both groups. The response rate at week 8 was higher than it at week 4 (P<0.05), and was no significant difference compared with it at week 26 (P>0.05) in both groups. Association was found between BMI and changes of NRS (P<0.05), but not between BMI and WOMAC function (P>0.05) in MA group, while no asscoaition was found between BMI and NRS or WOMAC function in EA group (P>0.05). There was no association found between other factors and NRS or WOMAC function in both groups (P>0.05). ConclusionFor KOA patients, 8-week acupuncture was more effective than 4-week acupuncture in relieving pain and improving joint function, but growth rate of the effect slowed down with increasing duration of intervention. It was uncertain whether the long-term effect of 8-week acupuncture was better than 4-week acupuncture. Further studies are required to further determine the effect of duration of intervention.

Clinical and Radiographic Outcomes of Supramalleolar Osteotomy for the Old Age Patients with Medial Compartment Ankle Osteoarthritis

Category: Ankle Arthritis Introduction/Purpose: Supramalleolar osteotomy (SMO) has recently been accepted as the major surgical option for treating painful asymmetric ankle arthritis. However, in many literatures, old age is regarded as relative contraindication for SMO. This study aimed to evaluate clinical and radiographic outcomes of medial compartment ankle osteoarthritis (OA) treated with SMO for the patients of relatively old age. Also, the study is aimed to compare the outcomes between old age group (≥ 65 years) and the group younger than 65 years. Methods: The study is based on consecutive 60 ankles of medial compartment ankle arthritis (60 patients) with moderate to severe medial ankle pain (at least 1-year follow-up). SMO and fibular valgization oblique osteotomy were performed. As for the functional evaluation, visual analogue scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) ankle- hindfoot scores and ankle range of motion (ROM) were evaluated. On radiographs, tibial anterior surface angles (TAS), tibial lateral surface angles (TLS), and talar tilt angles (TT) were measured and the severity of ankle OA was classified by the Takakura stage. To evaluate how the age affects the outcomes of SMO procedures, the subjects were classified as two groups (Group 1: ≥ 65 years, 14 ankles, Group 2: &lt; 65 years, 46 ankles) and the comparison between the groups were made. Using second look arthroscopy, regeneration of articular cartilage was evaluated and compared between the groups. Results: The postoperative VAS pain score and ROM in group 1 were not inferior to those in group 2 (2.0 ± 2.0 vs 1.0 ± 1.4, p=0.949 / 50.7 ± 12.8 vs 52.0 ± 13.5, p=0.764). Also, the postoperative TLS angle and TT angle showed no significant difference between two groups. However, the postoperative AOFAS score was significantly higher in group 2 (79.0 ± 12.6 vs 88.0 ± 9.4, p&lt; 0.05). In terms of delayed union, there was no significant difference between two groups (3/14, 21.4% vs 9/46, 19.6%, p=0.818). As to complication rate, there was also no significant difference between two groups (1/14, 7.1% vs 6/46, 13.0%, p=0.899). There were no significant difference according to articular cartilage regeneration after SMO between two groups. Conclusion: SMO for the relatively older patients with painful medial compartment ankle OA achieved favorable clinical and radiological outcomes. In terms of osteotomy site union and complications, older age group (≥ 65 years) showed the results not inferior to those of younger age group ( &lt; 65 years). Even in the older age group, SMO could be one of the surgical options for the medial ankle OA.

Less pain reported 5 years after cementless compared to cemented unicompartmental knee replacement: an analysis of pain, neuropathy, and co-morbidity scores

PurposeTo compare patient-reported pain scores and assess the influence of neuropathy and co-morbidity, on knee pain following cemented and cementless medial unicompartmental knee replacement (UKR) 5 years after surgery.MethodIn this longitudinal study, 262 cemented and 262 cementless Oxford UKR performed for the same indications and with the same techniques were recruited. Patients were reviewed at five years, evaluating patient-reported pain and association with clinical outcomes. Intermittent and Constant Osteoarthritis Pain (ICOAP), PainDETECT (PD), Charnley score, Oxford Knee Score (OKS) and American Knee Society Score (AKSS) were compared.ResultsIn both cohorts, intermittent pain was more common than constant pain (47% vs 21%). Cementless knees reported significantly less pain than cemented (ICOAP-Total 5/100 vs 11/100, p < 0.0001). A greater proportion of cementless knees experienced no pain at all (ICOAP = 0/100, 61% vs 43%, p < 0.0001) and 75% fewer experienced severe or extreme pain. Pain sub-scores in PD, OKS and AKSS follow this trend. Pain was unlikely to be neuropathic (PD positive: 5.26%), but patients reporting high levels of ‘strongest’ pain were three times more likely to be neuropathic. Patients with co-morbidities (Charnley C) experienced greater pain than those without (Charnley A+B) across all knee-specific scores, despite scores being knee specific.ConclusionBoth cemented and cementless UKR in this study had substantially less pain than that reported in literature following TKR. Cementless UKR had significantly less pain than cemented UKR in all scores. Two-thirds of patients with a cementless UKR had no pain at all at 5 years, and pain experienced was most likely to be mild and intermittent with no patients in severe or extreme pain. Patients with cementless UKR that had higher levels of pain were more likely to have co-morbidity or evidence or neuropathic pain. It is unclear why cementless UKR have less pain than cemented; further study is necessary.

A systematic review of the psychometric properties of pressure pain detection threshold in evaluating mechanical pain threshold in people with hand or wrist injuries

PurposeThe aim of this study was to conduct a systematic review of the psychometric properties of Pressure Pain Detection Threshold (PPDT) measures in people with hand or wrist injuries. Study Design and MethodsMEDLINE, Embase, and CINAHL databases were searched to identify eligible studies evaluating psychometric properties of PPDT in samples composed of at least 50% of people with hand or wrist injury. The Consensus-based Standards for the Measurement of Health Instruments' risk of bias checklist was used to critically appraise the included studies, and qualitative synthesis was performed by pooling the results of all studies that presented the same measurement property using Grading of Recommendations, Assessment, Development, and Evaluation. ResultsFrom 415 studies, 11 relevant studies were identified. Of the 11 studies, four hand or wrist injuries were represented; carpal tunnel syndrome, distal radius fractures, osteoarthritis, and complex regional pain syndrome. Intra-rater reliability was considered sufficient (intraclass correlation coefficient 0.64-0.94), with small reported standard error of the mean values (5.3-39.2 kPa). Results of validity and responsiveness could not be synthesized due to heterogeneity. Risk of bias for reliability and measurement error was assessed as very good or adequate, whereas validity and responsiveness were doubtful or inadequate. Overall quality of evidence was low or very low for all measurement properties. ConclusionsInconsistent results and low quality evidence provide little confidence in the overall measurement properties of PPDT in a hand or wrist injury population. No criterion standard for pain further highlights complexities around pain measurement such that the results obtained from PPDT measures in clinical practice cannot be compared to a gold standard measure.

Role of Nigella sativa L. in the Management of Osteoarthritis: A Systematic Review

Because of the anti-inflammatory properties of thymoquinone (TQ), as the main bioactive substance of Nigella sativa L., this systematic review aimed at assessing the therapeutic effects of N. sativa and its main bioactive substance in the management of patients with osteoarthritis (OA) based on the in vivo, in vitro, and in clinical studies. The methodology was adjusted based on the Cochrane Handbook recommendations. All published articles focusing on N. sativa as a therapeutic agent for the treatment of OA or its animal model were searched up to 20 April 2022 in PubMed, Medline, Web of Sciences, and Scopus databases. The search process was carried out using the following keywords: "Nigella sativa", "Black seed', "Black cumin", and "Thymoquinone" in combination with "Osteoarthritis". Finally, 14 articles remained, including five intervention clinical trial, two human studies, and seven animal studies. Four of five intervention studies showed that N. sativa administration led to relief in pain intensity. In the other clinical trial, no difference was reported between the N. sativa and control groups in terms of pain relief among OA patients. Studies demonstrated the anti-inflammatory and chondroprotective effects of TQ as the main bioactive substance of N. sativa. The evidence confirmed the anti-inflammatory and chondroprotective effects of N. sativa in the management of OA patients. Considering the lack of significant adverse effects such as allergic reaction to N. sativa in the aforementioned studies, this substance can be recommended as a safe adjuvant treatment to relieve OA pain, compared to nonsteroidal anti-inflammatory drugs and other analgesics.

Anti-Osteoarthritic Effects of Antarctic Krill Oil in Primary Chondrocytes and a Surgical Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive cartilage destruction and synovitis; however, there are no approved disease-modifying OA drugs. Krill oil (KO) has been reported to possess anti-inflammatory properties and alleviate joint pain in knee OA, indicating its potential to target the inflammatory mechanism of OA. Therefore, the anti-OA effects of KO were investigated in primary chondrocytes and a surgical rat model of knee OA. The oral administration of KO at 200 and 100 mg/kg for 8 weeks improved joint swelling and mobility in the animal model and led to increased bone mineral density and compressive strength in the cartilage. The oral KO doses upregulated chondrogenic genes (type 2 collagen, aggrecan, and Sox9), with inhibition of inflammation markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in the cartilage and synovium. Consistently, KO treatments increased the viability of chondrocytes exposed to interleukin 1α, accompanied by the upregulation of the chondrogenic genes and the inhibition of the ECM-degrading enzymes. Furthermore, KO demonstrated inhibitory effects on lipopolysaccharide-induced chondrocyte inflammation. Histopathological and immunohistochemical analyses revealed that KO improved joint destruction and synovial inflammation, probably due to the anti-inflammatory, anti-apoptotic, and chondrogenic effects. These findings suggest the therapeutic potential of KO for knee OA.

Conditioned pain modulation and analgesia of local acupuncture for chronic musculoskeletal pain: An exploratory study

ObjectiveConditioned pain modulation (CPM) has been found to be inefficient in patients with chronic pain. Animal and human studies showed that CPM is involved in acupuncture analgesia. This study explored the relationship between the potency of CPM and the extent of acupuncture analgesia. Materials and methodsThirty-five (35) participants with chronic non-specific low back pain or knee osteoarthritis were given sessions of acupuncture treatment at the pain sites twice per week for four weeks. Participants were asked to complete a diary, before and after the treatment, to monitor changes in clinical pain intensity, daily pain duration and analgesic intake. The potency of CPM was assessed before and after the treatment course. Correlation between potency of CPM and extent of acupuncture analgesia was analysed. ResultsClinical average pain intensity (0.79 ± 1.09, p < 0.01), daily pain duration (1.45 ± 3.77 hr, p = 0.03) and analgesic intake (1.41 ± 3.96, p = 0.04) decreased significantly after treatment, while potency of CPM increased significantly (18.21 ± 49.94%, p = 0.04). Pearson correlations showed those with less efficient baseline CPM presented with better pain reduction after treatment. Those with less efficient baseline CPM were associated with greater improvement in potency of CPM after treatment (r = 0.60, p < 0.01). There was no association between the change in potency of CPM and the change in clinical pain intensity. ConclusionsIndividuals have varied acupuncture analgesia. People with less efficient baseline CPM would likely benefit from local acupuncture with greater pain relief and improved potency of CPM. Larger studies with a control arm are needed to confirm these results.

Computational linguistics and sentiment analysis of misconceptions in pharmacotherapy of osteoarthritis pain

Background. Osteoarthritis (OA) is one of the leading causes of chronic pain in adults, wherein half of the cases is coupled to a neuropathic component. Agents with chondroprotective properties such as chondroitin sulfate (CS) and glucosamine sulfate (GS) have been successfully used in the treatment of OA-related pain. CS/GS exhibit diverse analgesic, anti-inflammatory, antioxidant and chondroregenerative effects that contribute to the restoration of cartilage tissue.Objective: to analyze the misconceptions associated with the medical terminology used for CS/HS in the treatment of OA-related pain, approaches to standardize the quantitative and qualitative composition of CS/HS extracts.Material and methods. Expert analysis was performed along with computational linguistics methods (sentiment analysis, i.e. analysis of text-related emotional modality). Sentiment analysis was carried out using the topological theory of data analysis and algorithms, with 90% accuracy allowing to classify texts into 16 classes of sentiment (manipulative constructs, research without positive results, propaganda, data falsification, etc.). This technique was tested earlier on 20 million publications retrieved from PubMed/MEDLINE database.Results. In recent years, the use of highly dubious terms such as “symptomatic slow acting drug for osteoarthritis, SYSADOA”, etc., has been extensively promoted at certain international conferences. The introduction of such barely scientific terms is not justified neither by the results of basic research nor clinical practice. Using the methods of computational linguistics and data mining of the biomedical literature, we have shown that some misconceptions actively promoted at the so-called "grand conferences" and "international congresses" virtually lack in real-world published scientific literature. Such misconceptions, logically contradicting the entire system of other medical terms, confuse scientific terminology. Moreover, texts promoting this misconceptions are easily recognized as manipulative not only by experts in the analysis of medical literature, but also by artificial intelligence algorithms.Conclusion. A number of misconceptions associated with inadequate interpretation of data obtained during basic and clinical studies of CS/GS has been explored. Specific examples show how practitioners can distinguish between manipulative propaganda and a balanced presentation of research data.

Specification, validation, and adherence of quality indicators to optimize the safe use of nonsteroidal anti-inflammatory drugs for knee osteoarthritis pain in the primary care setting

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) used for osteoarthritis (OA) in primary care may cause gastrointestinal or renal injury. This study estimated adherence to two quality indicators (QIs) to optimize NSAID safety: add proton pump inhibitors (PPI) to NSAIDs for patients with gastrointestinal (GI) risk (QI #1 NSAID-PPI) and avoid oral NSAIDs in chronic kidney disease (CKD) stage G4 or G5 (QI #2 NSAID-CKD).MethodsThis retrospective study included index primary care clinic visits for knee OA at our health system in 2019. The validation cohort consisted of a random sample of 60 patients. The remainder were included in the expanded cohort. Analysis of structured data extracts was validated against chart review of clinic visit notes (validation cohort) and estimated QI adherence (expanded cohort).ResultsAmong 60 patients in the validation cohort, analysis of data extracts was validated against chart review for QI #1 NSAID-PPI (100% sensitivity and 91% specificity) and QI #2 NSAID-CKD (100% accuracy). Among 335 patients in the expanded cohort, 44% used NSAIDs, 27% used PPIs, 73% had elevated GI risk, and only 2% had CKD stage 4 or 5. Twenty-one percent used NSAIDs and had elevated GI risk but were not using PPIs. Therefore, adherence to QI #1 NSAID-PPI was 79% (95% CI, 74–83%). No patients with CKD stage 4 or 5 used NSAIDs. Therefore, adherence to QI #2 NSAID-CKD was 100%.ConclusionA substantial proportion of knee OA patients with GI risk factors did not receive PPI with NSAID therapy during primary care visits.

Subgrouping of facilitatory or inhibitory conditioned pain modulation responses in patients with chronic knee pain. Explorative analysis from a multicentre trial.

Facilitatory and inhibitory conditioned pain modulation (CPM) responses are observed in healthy volunteers and chronic pain patients, but the clinical implications for phenotyping are unknown. This study aimed to subgroup and compare chronic knee pain patients according to their CPM responses. This explorative, cross-sectional study included 127 patients with chronic knee pain (osteoarthritis or following total knee arthroplasty). Individual CPM responses were categorized as facilitatory (test stimuli pain intensity increased when conditioning stimuli were applied), as inhibitory (test stimuli pain intensity decreased) or as no change (defined as less than 5.3% change in pain intensity). Outcomes were clinical pain intensities, temporal summation, widespread pain, self-reported physical function, PainDETECT questionnaire and Pain Quality Assessment Scale. Data were analysed as comparisons between the inhibitory and the facilitatory groups and using multivariate linear regression models. Fifty-four patients had facilitatory CPM responses, 49 had inhibitory CPM responses, and 24 showed no change in CPM response. A between-group difference was observed for self-reported physical function, with the facilitatory CPM group reporting better function (54.4 vs. 46.0, p = 0.028) and the facilitatory CPM group reported more deep pain sensations (3.2 vs. 2.0, p = 0.021). The remaining outcomes showed no between-group differences. Higher clinical pain intensity and facilitated temporal summation were associated in the facilitated CPM group but not in the inhibitory CPM group. These explorative findings indicated that quantitative clinical and experimental differences exist between facilitatory or inhibitory CPM responses in a chronic knee pain patient population. Differences in patients' CPM responses should be further investigated to unravel possible clinical importance. Our findings confirm that conditioned pain modulation consist of inhibitory and facilitatory responders among a patient population with chronic knee pain. This explorative study indicates that patients with either facilitatory or inhibitory conditioned pain modulation could exhibit differences in pain outcomes. Subgrouping of chronic pain patients depending on individual conditioned pain modulation responses could be considered in phenotyping patients prior to inclusion in clinical trials or used for personalizing the management regime.

Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway.

Chronic pain caused by persistent inflammation is current in multiple diseases and has a strong negative impact on society. It is commonly associated with several mental illnesses, which can exert a negative influence on pain perception, and needs to be eradicated. Nevertheless, actual therapies are not sufficiently safe and effective. Recent reports demonstrate that the induction of heme oxygenase-1 (HO-1) enzyme produces analgesic effects in animals with osteoarthritis pain and reverses the grip strength loss caused by sciatic nerve crush. In this research, we evaluated the potential use of three new HO-1 inducers, 1m, 1a, and 1b, as well as dimethyl fumarate (DMF), for treating persistent inflammatory pain induced by the subplantar injection of complete Freud's adjuvant and the functional deficits and emotional sickness associated. The modulator role of these treatments on the inflammatory and antioxidant pathways were also assessed. Our findings revealed that repeated treatment, for four days, with 1m, 1a, 1b, or DMF inhibited inflammatory pain, reversed grip strength deficits, and reversed the linked anxious- and depressive-like behaviors, with 1m being the most effective. These treatments also suppressed the up-regulation of the inflammasome NLRP3 and activated the expression of the Nrf2 transcription factor and the HO-1 and superoxide dismutase 1 enzymes in the paw and/or amygdala, thus revealing the anti-inflammatory and antioxidant capacity of these compounds during inflammatory pain. Results suggest the use of 1m, 1a, 1b, and DMF, particularly 1m, as promising therapies for inflammatory pain and the accompanying functional disabilities and emotional diseases.

Comparison of the efficacy of genicular nerve phenol neurolysis and radiofrequency ablation for pain management in patients with knee osteoarthritis.

: Genicular nerve neurolysis with phenol and radiofrequency ablation (RFA) are two interventional techniques for treating chronic refractory knee osteoarthritis (KOA) pain. This study aimed to compare the efficacy and adverse effects of both techniques. : Sixty-four patients responding to diagnostic blockade of the superior medial, superior lateral, and inferior medial genicular nerve under ultrasound guidance were randomly divided into two groups: Group P (2 mL phenol for each genicular nerve) and Group R (RFA 80°C for 60 seconds for each genicular nerve). The numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate the effectiveness of the interventions. : RFA and phenol neurolysis of the genicular nerves provided effective analgesia within groups at 1 week, 1 month, and 3 months compared to baseline. There was no significant difference between the groups in terms of NRS and WOMAC scores at all measurement times. At the 3rd month follow-up, 50% or more pain relief was observed in 53.1% of patients in Group P and 50% of patients in Group R. The rate of transient paresthesia was 34.4% in Group P and 6.3% in Group R, and this was significantly higher in Group P. : Neurolysis of the genicular nerves with both RFA and phenol is effective in the management of KOA pain. Phenol may be a good alternative to RFA. Further studies are needed on issues such as dose adjustment to prevent transient paresthesia response.

Efficacy of Transcutaneous 4.4 MHz Radiofrequency Diathermy versus Therapeutic Ultrasound for Pain Relief and Functional Recovery in Patients with Knee Osteoarthritis: A Randomized Controlled Study.

Knee osteoarthritis (KOA) is a prevalent common cause of disability and pain among adults. Transcutaneous radiofrequency (RF) diathermy and therapeutic ultrasound (US) are commonly employed treatments for addressing musculoskeletal conditions. This study aims to evaluate and compare the clinical effectiveness of transcutaneous 4.4 MHz RF diathermy and therapeutic US therapy in individuals diagnosed with KOA. A total of 108 patients with KOA were randomly assigned to either the RF or US groups. Each participant underwent a series of 10 treatment sessions over four weeks and was evaluated at different time points. The assessments included physical evaluations, vital sign measurements, the Numeric Rating Scale (NRS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, the Lequesne index, gait analysis, the 36-Item Short Form Health Survey (SF-36), and analysis of adverse responses. Both groups showed significant differences in NRS, WOMAC scores, and Lequesne index compared to baseline values at both the 10th treatment session and the one-month follow-up assessment. However, no significant disparities were observed between the two groups at each assessment point. In the gait analysis, following the 10th treatment, the RF group showed significant changes in stride length and stride velocity compared to baseline. Four weeks after the completion of treatment, both groups exhibited significant alterations in stride length and stride velocity when compared to baseline measurements. However, regarding cadence, only the RF group exhibited a significant difference compared to baseline. The findings suggest that transcutaneous 4.4 MHz RF diathermy displays a comparable effectiveness to therapeutic US in reducing pain and enhancing functional capacity among individuals with KOA. Further research endeavors are warranted to advance the efficacy of noninvasive treatments for KOA.

Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis

Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis.

Features of Knee and Multijoint Osteoarthritis by Sex and Race and Ethnicity: A Preliminary Analysis in the Johnston County Health Study.

To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort. Participants (n = 544) enrolled in the Johnston County Health Study (JoCoHS) as of January 2023 were categorized by radiographic and symptomatic KOA and MJOA phenotypes, and frequencies were compared by sex and race and ethnicity. Symptoms were assessed according to the Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain, aching, and stiffness (PAS) scores at various joints. Models produced estimates (odds ratio [OR] or mean ratios [MR] and 95% CI) adjusted for age, BMI (kg/m2), and education. Men had twice the odds of having MJOA-6 (≥ 3 lower extremity joints affected); there were no significant differences in MJOA phenotypes by race and ethnicity. Women had 50% higher odds of having KOA or having various features of KOA. Women reported significantly worse KOOS Symptoms scores (MR 1.25). Black participants had higher odds of more severe KOA (OR 1.47), subchondral sclerosis (OR 2.06), and medial tibial osteophytes (OR 1.50). Black participants reported worse KOOS Symptoms than White participants (MR 1.18). Although not statistically significant, Hispanic participants (vs non-Hispanic participants) appeared to have lower odds of radiographic changes but reported worse symptoms. Preliminary findings in the diverse JoCoHS cohort suggest more lower extremity- predominant MJOA in men compared to women. Women and Black participants had more KOA features and more severe symptoms. Hispanic participants appear to have higher pain and symptoms scores despite having fewer structural changes. Studies in diverse populations are needed to understand the burden of OA.

Evaluation of the hoof centre-of-pressure path in horses affected by chronic osteoarthritic pain.

The Centre of Pressure (COP) is the single point summarising all forces transferred to the hoof during the stance phase of a stride. COP path (COPp) is the trajectory that COP follows from footstrike to lift-off. Aim of the present study was to characterize the COP and COPp in horses affected by osteoarthritis and chronic lameness. Seventeen adult horses with a diagnosis of osteoarthritis and single limb chronic lameness were recruited. The COP was recorded using a wireless pressure measuring system (TekScan®) with sensors taped to the hooves (either fore- or hind limb, depending on lameness location). The COPp coordinates were further processed. Procrustes analysis was performed to assess the variability of single strides COPp and average COPp among strides, gaits, and limbs by calculating Procrustes distances (D-values). A linear mixed-effects model was run to analyse D-values differences for lame and sound limbs. Additionally, average COPp D-values and COPp hoofprint shape indices were compared for lame and sound limbs with the Signed Rank Test. At walk and trot the single-stride COPp D-values were significantly lower in lame than in sound limbs (marginal effects p<0.001). Analysis of the average COPp D-values confirmed that each hoof COPp is highly consistent with itself over subsequent trials but is different from the contralateral. COPp and hoofprint shape indices did not differ between sound and lame limbs. Footstrike and lift-off within the hoofprint showed that most horses had lateral footstrike and lift-off, independently of the lameness location. Our findings are in line with previous observations that COPp are highly repetitive and characteristic for each horse and limb. There seems to be a further decrease in COPp variability in the presence of a painful limb pathology.