Osteoarthritis Pain Research Articles

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple Food and Drug Administration-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics—invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. We have identified a key regulator of CaV2.2 channels, collapsin response mediator protein 2, that allows us to indirectly regulate CaV2.2 expression and function. We previously developed a peptidomimetic modulator of collapsin response mediator protein 2, CBD3063, that effectively reverses neuropathic and inflammatory pain without negative side effects by reducing membrane expression of CaV2.2. The potent analgesic properties of CBD3063, combined with the lack of negative side effects, prompted us to assess the efficacy of CBD3063 in a rodent model of OA pain. Here, we demonstrate the intraperitoneal administration of CBD3063 alleviates both evoked and nonevoked behavioral hallmarks of OA pain. Further, we reveal that CBD3063 reduces OA-induced increased neural activity in the parabrachial nucleus, a key supraspinal site modulating the pain experience. Together, these studies suggest that CBD3063 is an effective analgesic for OA pain. PerspectiveDespite the high prevalence of OA pain worldwide, current treatment options remain limited. We demonstrate that CBD3063-mediated disruption of the CaV2.2-collapsin response mediator protein 2 interaction alleviates pain in a preclinical joint pain model, providing a promising basis for the development of new OA pain treatments.

Effectiveness of Intra-articular Botulinum Toxin Type A with Hyaluronic Acid Compared to Intra-articular Platelet-rich Plasma with Hyaluronic Acid in Improving Pain and Functional Limitation in Knee Osteoarthritis

Abstract Background: Knee osteoarthritis (KOA) is the most common cause of chronic knee pain causing functional disability and dependency. Multiple interventions have been used in reducing pain and improving functionality. We intend to compare the efficacy of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) with botulinum toxin type A and HA in bilateral Grade 3 and 4 KOA. Methods: Prospective single-blinded randomized controlled trial conducted for 6 months. Among 54 participants, 27 received intra-articular botulinum toxin type A with HA (Group A), and the other 27 received intra-articular PRP with HA (Group B), single session. Pain (Numerical Rating Scale [NRS]) and functional limitation (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were assessed at 2, 4, 12, and 24 weeks postintervention. Effect of weight and physiotherapy on NRS and WOMAC score were assessed. P <0.05 was considered statistically significant. Data were analyzed by statistical software R version 4.2.3. Results: Fifty-four participants were enrolled. There was no loss to follow-ups. Except for age (P < 0.001) and mean height (P = 0.013), other demographic data were insignificant. Preprocedural NRS was significantly high in Group A (P = 0.04). Overall NRS postprocedure was significantly lesser in Group B, P < 0.001. The mean WOMAC score postprocedure was significantly low in Group B, P < 0.001. Group B had increased heart rate which was statistically significant (P = 0.051). The mean reduction in WOMAC score was observed with regular physiotherapy in Group B (P = 0.023). Reduction in weight was directly proportional to reduction in NRS (P = 0.015). Conclusion: Intra-articular PRP with HA, single session, is effective in improving pain, functionality, and safe in Grade 3 and 4 KOA.

Gut Microbiomics of Sustained Knee Pain in Knee Osteoarthritis Patients.

To examine whether gut microbes were associated with post-surgery sustained knee pain in knee osteoarthritis (OA) patients by a gut microbiomics approach. Total knee replacement (TKR) patients due to primary knee OA were recruited. Sustained knee pain status at least one year after TKR was defined by the Western Ontario and McMaster University Arthritis Index (WOMAC). Fasting plasma sample and fecal sample were collected. Metabolomic profiling was performed on fasting plasma. 16S rRNA sequencing was performed on fecal samples to determine microbial composition. Twenty TKR patients due to primary knee OA were included in the study with 10 experiencing sustained post-surgery pain and 10 without such pain. Age, sex, and BMI were matched. Linear discriminant analysis of microbiome data identified 13 bacterial taxa that were highly abundant in the pain group, and 5 that were highly abundant in the non-pain group (all P < 0.05). Plasma metabolomic profiling measured 622 metabolites. The correlation analysis indicated that the 18 taxa were significantly correlated with 231 metabolites (all P < 0.05). sPLS-DA analysis showed that 30 out of the 231 metabolites explained 29% of total variance and can be used to clearly separate sustained knee pain patients from non-pain patients. Pathway enrichment analysis showed that these significant metabolites were enriched in arachidonic acid metabolic pathway, bile acid biosynthesis, and linoleic acid metabolism. The gut microbes may play a significant role in sustained knee pain in knee OA patients after TKR potentially through their activation of inflammatory pathways, lipid metabolism, and central sensitization.

Prevalence and Factors Associated With High-Impact Chronic Pain in Knee Osteoarthritis: The Johnston County Health Study

Pain is a hallmark symptom of knee osteoarthritis (KOA), yet intensity and severity vary widely among individuals. There is a knowledge gap in understanding key characteristics of high-impact chronic pain (HICP) within the context of KOA. Therefore, our first purpose was to examine the prevalence of HICP in a cohort of individuals with radiographic evidence of KOA, and our second purpose was to assess patient-level factors associated with HICP. Data from the Johnston County Health Study were used to compare those with and without HICP. Variables included sociodemographic factors, clinical factors, health care use, and psychosocial distress. HICP status was classified with Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function measures. The results indicated that 15.5% (48/310) of participants were classified as having HICP when the PROMIS-Pain Interference cutoff score was used, while 21.2% (66/310) were classified as having HICP with a PROMIS-Physical Function cutoff score. Multivariable analyses indicated that HICP was consistently characterized by increased kinesiophobia and somatization, regardless of PROMIS measure used for HICP status. A secondary insight was that HICP was not consistently characterized by sociodemographic and clinical variables, as these findings were dependent on PROMIS measure used. These findings could be used to develop intervention approaches specific to individuals with KOA and to inform future investigations of sociodemographic and clinical factors associated with HICP. PerspectiveThese findings provide additional information on the characterization of HICP for individuals with KOA. There was consistency in psychosocial factors associated with HICP, while sociodemographic and clinical factors varied based on how HICP status was defined.

The Interplay of Microbiota, Long COVID, and Musculoskeletal Pain: A Narrative Review

Context: Long COVID, a condition that persists after the acute phase of COVID-19, poses a significant burden, with 10 - 45% of recovered patients experiencing persistent symptoms. Among these, approximately 46% report musculoskeletal pain. This narrative review explores the potential connections between gut microbiota, Long COVID, and musculoskeletal pain, aiming to introduce new therapeutic avenues and preventive strategies for managing musculoskeletal symptoms in Long COVID patients. Evidence Acquisition: A comprehensive search was conducted using Google Scholar, Lens.org, and ConnectedPaper.com to identify relevant articles published between 2019 and 2024. Keywords related to microbiota, Long COVID, and musculoskeletal pain were used. Articles were selected based on predefined inclusion and exclusion criteria, and their quality was assessed. Data from the selected articles were synthesized to provide an overview of the interplay between microbiota, Long COVID, and musculoskeletal pain. Results: Recent research highlights the significant role of gut microbiota in modulating immune responses and systemic inflammation. Dysbiosis has been linked to the severity and progression of COVID-19 and the persistence of Long COVID symptoms. Individuals with Long COVID often experience new-onset musculoskeletal manifestations, such as joint pain, myalgia, and chronic musculoskeletal pain. Additionally, gut dysbiosis has been associated with conditions like lower back pain and knee osteoarthritis. This suggests that the relationship between gut dysbiosis and musculoskeletal problems in general may also extend to musculoskeletal pain in Long COVID patients, indicating broader implications for musculoskeletal outcomes. Therapeutic strategies targeting the gut microbiota, such as probiotics, prebiotics, and dietary interventions, have shown promise in managing these symptoms and improving overall health outcomes. Conclusions: The evidence underscores the importance of understanding the microbiota-musculoskeletal nexus in Long COVID. Gut dysbiosis contributes to systemic inflammation, exacerbating musculoskeletal symptoms in Long COVID patients. The associations between gut dysbiosis and other musculoskeletal conditions emphasize the need for microbiota-targeted therapeutic strategies. Future research should focus on elucidating the mechanisms linking gut dysbiosis to musculoskeletal pain, exploring the gut-brain axis, and developing personalized approaches to modulate the microbiota. Advancing our understanding of this nexus can pave the way for innovative therapeutic strategies to address the complex health challenges posed by Long COVID and other musculoskeletal conditions.

Efficacy of arch contouring foot orthoses for midfoot osteoarthritis: Protocol for a randomised controlled trial.

Midfoot osteoarthritis (OA) is a painful and disabling condition. Arch contouring foot orthoses have been recommended for midfoot OA, yet there is no high-quality evidence from randomised controlled trials to support their use. This clinical trial aims to evaluate the efficacy of arch contouring foot orthoses for midfoot OA. This will be a parallel-group randomised controlled superiority trial. One-hundred and forty community-dwelling people with painful midfoot OA will be randomised to receive either arch contouring foot orthoses or flat sham inserts. Outcome measures will be obtained at baseline, 4, 8 and 12weeks; the primary endpoint for assessing efficacy being 12weeks. The primary outcome measure will be average midfoot pain whilst walking over the last 7days on an 11-point numerical rating scale. Secondary outcome measures include function (walking/standing subscale of the Manchester-Oxford Foot Questionnaire), participants' perception of overall treatment effect (self-reported global rating of change on a 15-point Likert scale), physical activity (Incidental and Planned Exercise Questionnaire), general health-related quality of life (Short Form-12 Version® 2.0), use of co-interventions and adverse events. This trial will evaluate the efficacy of arch contouring foot orthoses for relieving pain and improving function, physical activity and health-related quality of life in people with midfoot OA. The findings will provide high-quality evidence as to whether arch contouring foot orthoses are efficacious and will help to inform clinical guidelines about the use of foot orthoses for midfoot OA. Australian and New Zealand Clinical Trial Registry (ACTRN12623000953639).

Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial.

Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. To assess symptomatic benefits of methotrexate in knee OA (KOA). A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). 15 secondary care musculoskeletal clinics in the United Kingdom. A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. Versus Arthritis.

Transcutaneous Pulsed Radiofrequency Treatment in Patients with Osteoarthritis of the Upper Extremity

Background: Non-invasive treatment options are preferred for managing upper extremity pain due to osteoarthritis (OA). Transcutaneous pulsed radiofrequency (TcPRF) is a promising technique and appears effective in managing knee and shoulder pain. Objectives: To investigate whether TcPRF treatment is effective in reducing pain and safe to use among patients with OA of the upper extremity. Methods: In this retrospective study, patients with painful OA of the upper extremity who underwent TcPRF treatment from February 2021 to February 2022 were included. The primary outcome measure was the change in NRS pain scores between baseline and 1, 2, and 6 weeks of follow-up. Secondary outcome measures included adverse events. Data were extracted from electronic medical records and via telephone consultation after the 6-week follow-up. Results: A total of 41 initial TcPRF treatments were performed among 37 patients. The NRS score at rest showed a statistically significant improvement at 6 weeks [median = 5 [interquartile range (IQR) 2 - 8)] compared with baseline [median = 6 (IQR 4 - 8)], P = 0.023, with a moderate effect size, r = -0.44. For NRS scores during activity, all follow-up moments had lower NRS scores [median = 7 (IQR 5 - 8)] than before TcPRF [median = 8 (IQR 7 - 9)], P = 0.002 - 0.006, with moderate to large effect sizes, r = -0.45 to r = -0.51. No adverse events were reported. Conclusions: Transcutaneous pulsed radiofrequency treatment is effective in reducing pain and is safe to use among patients with upper extremity pain due to OA.

The combined application of pulsed electromagnetic fields and platelet-rich plasma in the treatment of early-stage knee osteoarthritis: A randomized clinical trial.

This study aims to evaluate the therapeutic efficacy of combined treatment with pulsed electromagnetic fields (PEMFs) and platelet-rich plasma (PRP) injection in improving pain and functional mobility among patients with early-stage knee osteoarthritis (KOA). We hypothesize that this combined therapy can yield superior treatment outcomes. Based on the different treatment regimens, we divided 48 patients diagnosed with Kellgren-Lawrence grades I-III KOA into 3 groups: the PRP group, the PEMFs group, and the PRP + PEMFs group. Each subtype of KOA patients was randomly assigned to different treatment groups. In the PRP group, patients received intra-articular injections of leukocyte-rich platelet-rich plasma once a month for 3 consecutive months. In the PEMFs group, patients receive low-frequency PEMFs irradiation therapy with a frequency of 30 Hz and intensity of 1.5 mT, once daily, 5 times a week, for a consecutive treatment period of 12 weeks. In the PRP + PEMFs group, patients receive both of the aforementioned treatment protocol. The treatment effects on patients are evaluated at baseline and at weeks 4, 8, and 12 post-treatment. Assessment parameters include visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne Index score, and knee joint range of motion. From the 4th to the 12th week of treatment, the visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis Index scores, and Lequesne index scores of patients in all 3 groups gradually decreased, while knee joint mobility gradually increased (P < .05). At weeks 4, 8, and 12 after treatment, the PRP combined with PEMFs group showed significantly better scores compared to the PRP group and the PEMFs group, with statistically significant differences (P < .05). A total of 7 patients experienced adverse reactions such as knee joint swelling, low-grade fever, and worsening knee joint pain after treatment, all of which disappeared within 1 week after treatment. The incidence of complications did not differ significantly among the 3 groups (P = .67). PRP, PEMFs, and the combination of PRP and PEMFs therapy all effectively alleviate knee joint pain and improve joint function. However, compared to single treatment modalities, the combined therapy of PRP and PEMFs demonstrates more pronounced efficacy.

TRPA1 aggravates osteoclastogenesis and osteoporosis through activating endoplasmic reticulum stress mediated by SRXN1

Osteoporosis (OP) is a disorder of bone remodeling caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, inhibiting excessive osteoclast activity is one of the promising strategies for treating OP. A major transient receptor potential cation channel, known as transient receptor potential ankyrin 1 (TRPA1), was found to alleviate joint pain and cartilage degeneration in osteoarthritis. However, little research has focused on TRPA1 function in OP. As a result, this study aimed to explore the TRPA1 characteristics and its potential therapeutic function during osteoclastogenesis. The TRPA1 expression gradually increased in the osteoclast differentiation process; however, its suppression with small interfering RNA and an inhibitor (HC030031) significantly controlled the osteoclast count and the expression of osteoclast characteristic genes. Its suppression also inhibited endoplasmic reticulum (ER) stress-related pancreatic ER kinase (PERK) pathways. An ER stress inhibitor (thapsigargin) reversed the down-regulated levels of ER stress and osteoclast differentiation by suppressing TRPA1. Transcriptome sequencing results demonstrated that TRPA1 negatively regulated reactive oxygen species (ROS) and significantly increased the expression of an antioxidant gene, SRXN1. The osteoclast differentiation and the levels of ER stress were enhanced with SRXN1 inhibition. Finally, TRPA1 knockdown targeting macrophages by adeno-associated virus-9 could relieve osteoclast differentiation and osteopenia in ovariectomized mice. In summary, silencing TRPA1 restrained osteoclast differentiation through ROS-mediated down-regulation of ER stress via inhibiting PERK pathways. The study also indicated that TRPA1 might become a prospective treatment target for OP.

Application of the grading system for "nociplastic pain" in chronic primary and chronic secondary pain conditions: a field study.

The concept "nociplastic pain" has been developed for patients with features of nociceptive system sensitization that are not explained as nociceptive or neuropathic. Here, we tested how well the recently published grading system differentiates between chronic primary and secondary pain conditions. We recruited patients with fibromyalgia (FMS, n = 41), complex regional pain syndrome (CRPS, n = 11), osteoarthritis (OA, n = 21), or peripheral nerve injury (PNI, n = 8). We used clinical history, pain drawings, quantitative sensory testing (QST), and questionnaires to classify their pains as possibly or probably "nociplastic." All patients with chronic primary pain exhibited widespread/regional pain not explainable by either nociceptive or neuropathic mechanisms. Widespread pain occurred in 12 patients with OA but was identified as nociceptive in 11 of 12. Regional pain occurred in 4 patients with PNI but was identified as neuropathic in 3 of 4. At this step, the grading system had 100% sensitivity and 93% specificity. Clinical evidence for pain hypersensitivity by QST, and history of hypersensitivity and mental comorbidities did not differentiate between chronic primary pain (QST: 36/52 = 69%, history: 43/52 = 83%) and secondary pain conditions (QST: 20/29 = 69%, history: 24/29 83%). Based on these data, specificity remained excellent (93%), but sensitivity dropped substantially (60%) due to lacking evidence for pain hypersensitivity in many patients with FMS. This low sensitivity suggests that the published grading system is not suitable for screening purposes. We suggest structural and content modifications to improve sensitivity, including placement of patient history before clinical examination and addition of a high tender point count as evidence for widespread pain hypersensitivity.

Comparison of nociceptor properties using electrophysiology in preclinical models of osteoarthritis

Osteoarthritis (OA) pain originates in the joint by sensitization of articular nociceptors. While behavioural assessments provide valuable information regarding pain symptoms, the techniques are subjective and open to interpretation by the experimenter. This study used in vivo electrophysiological approaches to measure objectively joint nociceptor properties in three rodent models of OA. Single unit extracellular recordings of joint mechanosensitive afferents were carried out in male and female rats following either (1) transection of the medial meniscus (MMT: post-traumatic OA), (2) intra-articular injection of sodium monoiodoacetate (MIA: chemically-induced OA), or (3) intra-articular injection of lysophosphatidic acid (LPA: neuropathic OA). In naïve male control rats, the mechanical threshold of joint mechanonociceptors (23.5 ± 1.8 mNm) was significantly reduced with MMT (9.4 ± 1.1 mNm) and MIA (15.1 ± 1.6 mNm). In females, the mechanical threshold of naïve rats (23.2 ± 3.1 mNm) was reduced following induction of MMT (8.3 ± 1.0 mNm) and LPA (10.6 ± 2.2 mNm). Afferent firing frequency increased in male MMT (∼275 %), LPA (∼175 %), MIA (225 %), and female MMT (∼146 %), LPA (∼200 %), and MIA (∼192 %). Mechanical threshold and evoked firing were negatively correlated in all models for both sexes except LPA rats (male + female) and female MMT. These data indicate that MMT, MIA, and LPA induce peripheral sensitization of joint afferents thereby validating their use in OA pain studies.

Refixation of aposterior medial root lesion in combination with centralization by ameniscotibial suture

Refixation of aposterior root lesion of the medial meniscus via atibial drill tunnel and prevention of extrusion using ameniscotibial suture (centralization). Posterior root lesion of the medial meniscus. Grade4 cartilage damage in the corresponding compartment, uncorrected varus or valgus deformities, symptomatic instabilities, extensive degenerative tears apart from the root region. Knee arthroscopy via the high anterolateral standard portal. Diagnostic arthroscopy to check indication. Locate the insertion zone on the tibial plateau and local debridement until the bone of the tibial plateau is visible. Insertion of atargeting device and drilling of atargeting wire into the center of the insertion zone in the area of the intercondylar eminence. Overdrill the target wire with a4.5 mm drill. Reinforcement of the medial meniscus posterior horn with braided suture material. The reinforcing thread is inserted into the bone tunnel via an eyelet wire with athread loop. Optional additional centralization with incision in the middle part of the meniscus. Reinforcement of the meniscus base with braided suture material using the "outside in" technique and fixation of the inner meniscus base at the edge of the tibial plateau using atransosseous extraction suture or asuture anchor. Six weeks nonweight-bearing (0kg), then gradually increased load. Range of motion: 4weeks E/F 0-0-60°, 2weeks 0-0-90°, optionally use of avalgus brace (varus of < 5°). In root lesions of the medial meniscus, transosseous refixation significantly improves knee function (Lysholm, Hospital for Special Surgery, International Knee Documentation Committee, visual analog scale for pain, Tegner, and Knee Injury and Osteoarthritis Outcome scores) and reduces osteoarthritis progression. However, atransosseous suture alone could not significantly reduce postoperative extrusion. However, previous studies have shown that additional centralization can significantly reduce extrusion.

Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.

Osteoarthritis (OA) is a painful degenerative joint disease and a leading source of years lived with disability globally due to inadequate treatment options. Neuroimmune interactions reportedly contribute to OA pain pathogenesis. Notably, in rodents, macrophages in the DRG are associated with onset of persistent OA pain. Our objective was to determine the effects of acute systemic macrophage depletion on pain-related behaviors and joint damage using surgical mouse models in both sexes. We depleted CSF1R+ macrophages by treating male macrophage Fas-induced apoptosis (MaFIA) transgenic mice 8- or 16-weeks post destabilization of the medial meniscus (DMM) with AP20187 or vehicle control (10 mg/kg i.p., 1x/day for 5 days), or treating female MaFIA mice 12 weeks post partial meniscectomy (PMX) with AP20187 or vehicle control. We measured pain-related behaviors 1-3 days before and after depletion, and, 3-4 days after the last injection we examined joint histopathology and performed flow cytometry of the dorsal root ganglia (DRGs). In a separate cohort of male 8-week DMM mice or age-matched naïve vehicle controls, we conducted DRG bulk RNA-sequencing analyses after the 5-day vehicle or AP20187 treatment. Eight- and 16-weeks post DMM in male mice, AP20187-induced macrophage depletion resulted in attenuated mechanical allodynia and knee hyperalgesia. Female mice showed alleviation of mechanical allodynia, knee hyperalgesia, and weight bearing deficits after macrophage depletion at 12 weeks post PMX. Macrophage depletion did not affect the degree of cartilage degeneration, osteophyte width, or synovitis in either sex. Flow cytometry of the DRG revealed that macrophages and neutrophils were reduced after AP20187 treatment. In addition, in the DRG, only MHCII+ M1-like macrophages were significantly decreased, while CD163+MHCII- M2-like macrophages were not affected in both sexes. DRG bulk RNA-seq revealed that Cxcl10 and Il1b were upregulated with DMM surgery compared to naïve mice, and downregulated in DMM after acute macrophage depletion. Acute systemic macrophage depletion reduced the levels of pro-inflammatory macrophages in the DRG and alleviated pain-related behaviors in established surgically induced OA in mice of both sexes, without affecting joint damage. Overall, these studies provide insight into immune cell regulation in the DRG during OA.

Barriers and facilitators to using a clinical decision support tool for the management of osteoarthritis pain in patients undergoing hemodialysis: a qualitative study

BackgroundWhile osteoarthritis is a significant issue within the hemodialysis population and contributes to reduced quality of life, pain related to osteoarthritis is poorly managed by healthcare professionals (HCPs) in hemodialysis settings due to the absence of clinical guidance applicable to this population. The purpose of this study was to explore the perceptions of HCPs on the barriers and facilitators to using a clinical decision support tool for osteoarthritis pain management in the hemodialysis setting.MethodsA qualitative descriptive study was conducted. Purposeful and snowball sampling techniques were used to recruit hemodialysis clinicians from academic and community settings across multiple Canadian provinces. One-to-one interviews were conducted with clinicians using a semi-structured, open ended interview guide informed by the Theoretical Domains Framework, a behavior change framework. A general inductive approach was applied to identify the main themes of barriers and facilitators.ResultsA total of 11 interviews were completed with 3 nephrologists, 2 nurse practitioners and 6 pharmacists. Findings revealed 6 main barriers and facilitators related to the use of the clinical decision support tool. Alignment of the tool with practice roles emerged as a key barrier and facilitator. Other barriers included challenges related to the dialysis environment, varying levels of clinician comfort with pain medications, and limited applicability of the tool due to patient factors. An important facilitator was the intrinsic motivation among clinicians to use the tool.ConclusionsMost participants across the included hemodialysis settings expressed satisfaction with the clinical decision support tool and acknowledged its overall potential for improving osteoarthritis pain management among patients on hemodialysis. Future implementation of the tool may be limited by existing roles and practices at different institutions. Increased collaboration among hemodialysis and primary care teams may promote uptake of the tool.

Genicular nerve radiofrequency ablation practice patterns: A survey study of the International Pain and Spine Interventional Society

IntroductionChronic knee pain often results from degenerative conditions such as knee osteoarthritis (OA) and can worsen after surgical interventions like total knee arthroplasty (TKA). Knee OA affects approximately 86 million individuals globally, leading to decreased function, mobility limitations, and disability. While TKA is a common surgical treatment for refractory knee OA, though up to 20 % of patients experience chronic post-operative knee pain worse than their pre-operative pain. Genicular nerve radiofrequency ablation (GnRFA) has emerged as a promising intervention for knee OA pain unresponsive to conservative management and for chronic post-TKA pain. GnRFA is an evidence-based technique supported by multiple prospective cohort studies and randomized controlled trials (RCTs). However, practice patterns and GnRFA techniques vary, and no peer-reviewed publication has yet quantified these variations in real-world clinical practice. ObjectiveThis study aims to understand the practice patterns of interventional pain physicians regarding patient selection, use of prognostic blocks, imaging, nerve targets, GnRFA types, and GnRFA techniques in treating knee pain secondary to OA or persistent post-TKA pain. MethodsAn anonymous 29-question survey was distributed via electronic mail to members of the International Pain and Spine Intervention Society (IPSIS) from January 16, 2024, to February 29, 2024. The survey assessed practice patterns related to patient selection, prognostic block use, and GnRFA techniques. Data were collected and stored using REDCap software, with descriptive statistics calculated. ResultsA total of 150 completed surveys were analyzed, representing a completion rate of 2.0 % of surveys sent, 3.5 % of emails opened, and 56.8 % of those who clicked on the survey link. Respondents generally use common selection protocols regarding OA grade (Kelgren-Lawrence 3 and 4), duration of failed conservative care (3–6 months), a single anesthetic block paradigm, and use of fluoroscopic guidance for the GnRFA procedure. More variability was reported between respondents regarding the volume of anesthetic used during prognostic blocks, the threshold to consider a prognostic block “positive,” the technology used, and nerves targeted during the GnRFA procedure. ConclusionThe study provides valuable insights into the current practice patterns of GnRFA among interventional pain physicians. While there is consensus on some aspects of patient selection and procedural techniques, significant variability exists in prognostic block protocols and nerve targets for GnRFA. These findings highlight the need for further research to explore the long-term efficacy and safety of GnRFA and to standardize techniques and protocols across different practice settings, ultimately improving patient outcomes and quality of life. The low response rate may limit generalizability, and the survey did not include data on active tip sizes used for ablation or whether other procedures should be exhausted before resorting to GnRFA. Additionally, a survey to IPSIS membership only may not fully represent a diverse cohort of pain management specialists, potentially introducing sampling bias. Future studies should include members from a broader range of professional organizations to enhance representativeness.

IDENTIFYING RISK FACTORS FOR DISEASE PROGRESSION IN DEVELOPMENTAL DYSPLASIA OF THE HIP USING A CONTRALATERAL HIP MODEL

Developmental dysplasia of the hip can cause pain and premature osteoarthritis. However, the risk factors and timing for disease progression in young adults are not fully defined. This study identified the incidence and risk factors for contralateral hip pain and surgery after periacetabular osteotomy (PAO) on an index dysplastic hip.Patients followed for 2+ years after unilateral PAO were grouped by eventual contralateral pain or no-pain, based on modified Harris Hip Score, and surgery or no-surgery. Univariate analysis tested group differences in demographics, radiographic measures, and range-of-motion. Kaplan-Meier survival analysis assessed pain development and contralateral hip surgery over time. Multivariate regression identified pain and surgery risk factors. Pain and surgery predictors were further analyzed in Dysplastic, Borderline, and Non-dysplastic subcategories, and in five-degree increments of lateral center edge angle (LCEA) and acetabular inclination (AI).184 patients were followed for 4.6±1.6 years, during which 51% (93/184) reported hip pain and 33% (60/184) underwent contralateral surgery. Kaplan-Meier analysis predicted 5-year survivorship of 49% for pain development and 66% for contralateral surgery. Painful hips exhibited more severe dysplasia than no-pain hips (LCEA 16.5º vs 20.3º, p&lt;0.001; AI 13.2º vs 10.0º p&lt;0.001). AI was the sole predictor of pain, with every 1° AI increase raising the risk by 11%. Surgical hips also had more severe dysplasia (LCEA 14.9º vs 20.0º, p&lt;0.001; AI 14.7º vs 10.2º p&lt;0.001) and were younger (21.6 vs 24.1 years, p=0.022). AI and a maximum alpha angle ≥55° predicted contralateral surgery.5 years after index hip PAO, 51% of contralateral hips experience pain and 34% percent are expected to need surgery. More severe dysplasia, based on LCEA and AI, increases the risk of contralateral hip pain and surgery, with AI being a predictor of both outcomes. Knowing these risks can inform patient counseling and treatment planning.

Intramuscular Botulinum Toxin as an Adjunct to Arthrocentesis with Viscosupplementation in Temporomandibular Disorders: A Proof-of-Concept Case-Control Investigation.

The reduction in joint load is a potential beneficial factor in managing osteoarthritis of the temporomandibular joint (TMJ). This paper aims to compare the effectiveness of the intramuscular injection of botulinum toxin (BTX-A) as an adjunct to TMJ arthrocentesis plus viscosupplementation with arthrocentesis plus viscosupplementation alone in the management of TMJ osteoarthritis. A pilot clinical retrospective study examined TMJ osteoarthritis treatments. Patients were divided into two groups: Group A received BTX-A injections and arthrocentesis with viscosupplementation, while Group B received only arthrocentesis with viscosupplementation. The study assessed outcomes based on mouth opening (MO), pain at rest (PR), pain at mastication (PF), and masticatory efficiency (ME) at various time points (baseline (T0), 1 week (T1), 2 weeks (T2), 3 weeks (T3), and 4 weeks (T4)) up to 2 months after treatment. The study included two groups, each with five patients. Group A received five weekly sessions of arthrocentesis plus viscosupplementation and a single BTX-A injection during the first arthrocentesis appointment. Group B underwent the five-session protocol of arthrocentesis plus viscosupplementation alone. MO, PF, PR, and ME improved quickly in T2 in both groups, but the improvement was of greater importance over the following weeks and lasted longer in Group A. Arthrocentesis with viscosupplementation associated with BTX-A was found to be more effective than arthrocentesis alone in improving clinical outcomes. This suggests that patients with TMJ osteoarthritis and myofascial pain may benefit from reduced muscle tone and joint load.

Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study.

Osteoarthritis causes chronic pain, impaired joint function, decreased mobility and negatively impacts quality of life (QOL). Anti-nerve growth factor antibodies bedinvetmab for dogs and frunevetmab for cats are licensed for the alleviation of osteoarthritis pain but their QOL impact is unreported. Our aim was to determine if these therapeutics improve QOL using a validated health-related QOL measure that generates scores in four domains of QOL-energetic and enthusiastic (E/E), happy and content (H/C), active and comfortable (A/C) and calm and relaxed (C/R)-in the dog and three in the cat-vitality, comfort and emotional wellbeing (EWB). Summary scores for physical wellbeing (PWB) and emotional wellbeing (EWB) for dogs and PWB for cats are calculated from the domain scores. Animals received bedinvetmab (dogs) at 0.5-1 mg/kg or frunevetmab (cats) at 1-2.8 mg/kg by subcutaneous injection on days 0, 28 and 56 and owners completed QOL assessments within 48 hours of day 0 and on days 14, 28, 56, 63 and 70 using a study-specific app. Assessments were completed by 75 dog and 56 cat owners. By day 14 there was a statistically significant improvement (p ≤ 0.001) in PWB, EWB and all domains except C/R (p = 0.005) in dogs and in all domains and PWB in the cat. Subsequently there was a continued improvement in all domains and summary scores (p ≤ 0.001) except for H/C in the dog and EWB in the cat, which were excluded from the statistical model. The overall improvement in all domain scores in the cat and E/E and A/C in the dog exceeded the previously reported minimum important difference scores for the QOL measure, indicating a clinically significant change. Treatment with bedinvetmab and frunevetmab produced a significant improvement in the QOL of dogs and cats. This latest evidence for the use of these OA pain medications could be helpful in the clinical management of osteoarthritis and post-marketing clinical trials.

Exercise Training for Chronic Pain: Available Evidence, Current Recommendations, and Potential Mechanisms.

Chronic pain conditions pose a significant global burden of disability, with epidemiological data indicating a rising incidence. Exercise training is commonly recommended as a standalone or complementary approach for managing various chronic pain conditions like low back pain, osteoarthritis, rheumatoid arthritis, fibromyalgia syndrome, and neuropathic pain. Regardless of the specific condition or underlying cause (e.g., autoimmune disease, chronic inflammation), exercise training consistently leads to moderate to large reductions in pain. Moreover, exercise yields numerous benefits beyond pain alleviation, including small-to-moderate improvements in disability, quality of life, and physical function. Despite its efficacy, there is a lack of comprehensive research delineating the optimal intensity, duration, and type of exercise for maximal benefits; however, evidence suggests that sustained engagement in regular exercise or physical activity is necessary to achieve and maintain reductions in both clinical pain intensity ratings and the level that pain interferes with activities of daily living. Additionally, the precise mechanisms through which exercise mitigates pain remain poorly understood and likely vary based on the pathophysiological mechanisms underlying each condition.