Navigating the Mind Maze: How Can Musculoskeletal Clinicians Help Patients With Hip-Related Pain?

This infographic accompanies the editorial which critically evaluates how hip-related pain is currently managed, highlighting the limitations of traditional biomedical interventions alone in restoring optimal function and well-being. Psychological factors are key determinants of outcomes after surgical and nonsurgical treatment. We highlight the need for a holistic, patient-centered approach in evaluating and treating hip-related pain. Shifting to a holistic, patient-centered approach can improve treatment outcomes and reduce patient suffering. We guide readers to the impact of psychological factors on treatment outcomes, provide clinical considerations for how clinicians might approach psychologically informed practice, and outline future research directions. J Orthop Sports Phys Ther 2024;54(8):573. doi:10.2519/jospt.2024.9003.

Photobiomodulation therapy for chronic knee pain in obese patients in pre-rehabilitation for bariatric surgery: randomised, placebo-controlled, double-blinded, clinical trial protocol.

INTRODUCTION: Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain, especially in the knees, which increases significantly and proportionally with weight gain. In patients with severe obesity, with indication for bariatric surgery, the presence of chronic pain disables and often prevents their participation in a pre-surgical rehabilitation programme. As an analgesic therapy, photobiomodulation (PBM) has been studied with safety, efficacy, well-tolerated used and low costs. Thus, this study aims to evaluate the use of PBM for the treatment of chronic knee pain in obese patients undergoing a pre-surgical rehabilitation programme for bariatric surgery. METHODS AND ANALYSES: This is a double-blinded, randomised, placebo-controlled clinical, superiority, trial protocol. The PBM will be applied in bilateral knees and lumbar paraspinal points levels referring to the roots of innervation of the knee. The outcomes evaluated will be pain intensity, functionality, quality of life and clinical signs of neurological sensitization of chronic knee pain pathways. ETHICS AND DISSEMINATION: This protocol has already been approved by the Comitê de Ética em Pesquisa do Hospital das Clínicas da Universidade Federal de Goiás/EBSERH-Ethics Committee and it is following SPIRIT guidelines. The results will be statistically analysed and subsequently published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical Trials Platform (https://clinicaltrials.gov/) with the number NCT05816798.

Efficacy of Cooled-Radiofrequency Ablation of the Genicular Nerve as Treatment for Chronic Knee Pain: A Retrospective Study.

INTRODUCTION: Chronic pain is one of the leading causes of reduced quality of life in the USA, with knee pain commonly reported. Multiple therapeutic modalities are traditionally utilized for pain management; however, some patients may have pain refractory to these techniques. Cooled radiofrequency ablation (c-RFA) of the geniculate nerve is a growing and promising therapy offering a potentially long-term solution to chronic knee pain. METHODS: This study assessed the efficacy, average duration of relief, and potential adverse events using a retrospective chart review of 406 procedures. A two-tailed paired t test was used to assess the statistical significance between pre-RFA vs. post-RFA visual analog scale (VAS) pain scores self-reported by patients. An analysis of variance (ANOVA) test was used to evaluate for statistical differences in pre-RFA pain scores and post-RFA pain scores among the categories of age, sex, body mass index (BMI), and diagnosis group. RESULTS: The mean percent in pain improvement calculated was 65.5% with an average duration of relief of 7.20 months. The average pre-RFA pain score on the VAS was 6.26 out of 10 and 2.59 out of 10 post-RFA. The ANOVA post-RFA pain scores demonstrated statistically significant differences among the categories of age and sex. A total of 54 adverse events were reported, including worsening pain, numbness, paresthesia, and knee swelling. CONCLUSION: The study demonstrated that c-RFA can potentially be utilized as an alternative safe therapy for chronic knee pain, providing pain relief with a relatively prolonged duration. Inherent challenges of retrospective studies remain a part of the limitations of this study.

Central sensitivity syndrome affects the disease activity index and treatment satisfaction in patients with rheumatoid arthritis.

AIM: Many rheumatoid arthritis (RA) patients prioritize pain improvement in treatment. As pain can result from various causes, including noninflammatory factors such as central sensitivity syndrome (CSS), we hypothesized that CSS might impact treatment satisfaction. In this cross-sectional study, we assessed the CSS effects on clinical disease activity and treatment satisfaction in RA patients. METHODS: In total, 220 consecutive RA patients receiving long-term follow-up were evaluated for clinical disease activity and treatment satisfaction. CSS was evaluated using the Central Sensitization Inventory (CSI). An overall score of ≥40 indicates the presence of CSS. We queried "How satisfied are you with your treatment?"; answers included (a) very satisfied, (b) satisfied, (c) not satisfied, or (d) very dissatisfied. For univariate analysis, we condensed these answers into "dissatisfied" or "satisfied." We also evaluated treatment satisfaction using the visual analog scale (VAS), with scores ranging from 0 mm (very dissatisfied) to 100 mm (very satisfied). RESULTS: Of the 220 patients, 17 (7.7%) were classified as having CSS. CSI score was significantly correlated with the clinical disease activity index (CDAI; r = .322, p < .01) and treatment satisfaction (r = -.336, p < .01). Regarding treatment satisfaction, univariate analysis revealed that patient global assessment (PtGA), pain VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints with C-reactive protein, CDAI, and CSI scores of patients who were satisfied with treatment differed significantly from those of dissatisfied patients. Multivariate analysis revealed that CSI, PtGA, and HAQ-DI scores were associated with treatment satisfaction. CONCLUSION: In RA patients, CSS may affect the disease activity index and reduce treatment satisfaction.

Effectiveness of intra-articular infiltration of platelet concentrates for the treatment of painful joint disorders in the temporomandibular joint: a systematic review.

BACKGROUND: The role of Platelet-rich Plasma injections as a complementary therapy, together with other minimally invasive procedures, has been analyzed previously, however, there are no articles that evaluate the effects of intra-articular infiltration in the Temporomandibular Joint by itself. The aim of this article is to evaluate the effectiveness of intra-articular infiltration with Platelet-rich Plasma, as a single procedure, to both reduce pain and improve clinical parameters in painful joint disorders. MATERIAL AND METHODS: A systematic search was performed using the terms "Temporomandibular Joint Disorders" and "Platelet-rich plasma" in May 2021. Only the Clinical Trials found in the Pubmed/Medline, Embase, Cochrane Library/Cochrane CENTRAL, Google Scholar, and LILACS databases were selected. RESULTS: Only four articles were selected for full-text review. Statistically significant differences were found in pain reduction Platelet-rich Plasma-based interventions with respect to preoperative measurements up to six months. Only two studies found significant intergroup differences favoring Platelet-rich Plasma over other interventions. In relation to maximum mouth opening, three studies reported an increase compared to the preoperative measurements. CONCLUSIONS: Platelet-rich Plasma might potentially be effective in reducing pain levels and improving clinical parameters such as interincisal distance. However, studies with better methodological quality, larger sample sizes, and lower risk of bias are required to assess the real value of this intervention in the management of painful joint disorders.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial.

BACKGROUND: Chikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. OBJECTIVE: To evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. RESULTS: There was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. CONCLUSION: tDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.

Genicular artery embolization for the treatment of knee pain secondary to mild to severe knee osteoarthritis: One year clinical outcomes.

OBJECTIVE: To evaluate the safety and efficacy of genicular artery embolization (GAE) in patients with mild-to-severe knee osteoarthritis up to 12 months after GAE. MATERIALS & METHODS: This prospective single-center study included patients who had knee osteoarthritis for >1 year with moderate-to-severe pain after failed conservative treatment for >6 months. Baseline imaging features were evaluated to determine Kellgren-Lawrence (KL) grade and magnetic resonance imaging (MOAKS) scores. GAE was performed using 150-350 µm embolic polyvinyl alcohol particles. The visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate knee pain, stiffness, and function at baseline and follow-up. The primary endpoints were changes in VAS and WOMAC scores at 12 months. RESULTS: Thirty-three patients (n = 37 knees) aged 66.6 ± 8.7 years were enrolled. The patients were categorized into two groups: mild-to-moderate osteoarthritis (n = 28, KL grades 2-3) and severe osteoarthritis (n = 9, KL grade 4). GAE was successfully performed in all patients, with no major adverse events. Three to six branches of the genicular artery were embolized. The mean VAS and WOMAC scores in the mild-to-moderate group significantly decreased (6.6 at baseline vs. 3.0 at 12 months and 49.4 vs. 27.4, respectively, all P < 0.001). The mean VAS and WOMAC scores in the severe group significantly decreased at 12 months (7.3 vs. 4.4 and 58.1 vs. 40.6, respectively, all P < 0.001). CONCLUSION: GAE is a well-tolerated and effective treatment that significantly improves pain symptoms and function in patients with mild-to-severe knee osteoarthritis.

PENG for chronic pain: the clinical effectiveness of pericapsular nerve group block in chronic hip pain.

OBJECTIVES: To evaluate the efficiency and tolerability of pericapsular nerve group block (PENG) for the treatment of chronic hip pain. METHODS: This is a retrospective, single-centre, 4-group study conducted over a 3-month period to find out the most typical cause of chronic hip pain. A total of 112 patients with symptomatic hip osteoarthritis (OA), Stage 2-3, greater trochanteric pain (GTPS) and chronic pain after total hip arthroplasty (cTHA), who had an ultrasound-guided PENG block, were selected. To assess the effectiveness of the treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and visual analogue scale (VAS) scores of the patients prior to treatment were compared with their scores after the 1st week, 1st month, and 3rd month of treatment. The study also aimed to analyse the patients' initial feelings of alleviation following the block (1st VAS/2) and problems experienced both during and after the block. RESULTS: The parameters studied included pain, stiffness, and results of physical activity in the 1st week, 1st month, and 3rd month following PENG block application. At the beginning of the 1st week, of the 112 patients who were administered a PENG block for hip pain, we reported a 62% improvement in pain, a 52% reduction in stiffness, and a 53% increase in physical activity. Even though these results slightly declined in the 1st and 3rd months, the rates were still higher than 45%. CONCLUSIONS: Overall, the PENG block was well-tolerated by the patients in our study. No treatment-related infections or any other serious complications were observed.

Are the Effects of Resistance Exercise on Pain and Function in Knee and Hip Osteoarthritis Dependent on Exercise Volume, Duration, and Adherence? A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to determine dose parameters for resistance exercise associated with improvements in pain and physical function in knee and hip osteoarthritis (OA) and whether these improvements were related to adherence. METHODS: We searched six databases, from inception to January 28, 2023, for randomized controlled trials comparing land-based, resistance exercise-only interventions with no intervention, or any other intervention. There were four subgroups of intervention duration: 0 to <3 months, 3 to 6 months, >6 to <12 months, ≥12 months. The between-group effect was calculated for immediate postintervention pain and physical function (activities of daily living [ADL] and sports/recreation [SPORT]). RESULTS: For both knee and hip, data from 280 studies showed moderate benefit for pain, physical function ADL, and physical function SPORT in favor of interventions 3 to 6 months. For the knee, there was also a moderate benefit for physical function ADL in favor of interventions >6 to <12 months. From 151 knee and hip studies that provided total exercise volume data (frequency, time, duration), there was no association between volume with the effect size for pain and physical function. A total of 74 studies (69 knee, 5 hip) reported usable adherence data. There was no association between adherence with the effect size for pain and physical function. CONCLUSION: In knee and hip OA, resistance exercise interventions 3 to 6 months (and for the knee >6 to <12 months) duration improve pain and physical function. Improvements do not depend on exercise volume or adherence, suggesting exercise does not require rigid adherence to a specific dose.

Does the Combination of Platelet-rich Plasma and Supervised Exercise Yield Better Pain Relief and Enhanced Function in Knee Osteoarthritis? A Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis is a leading cause of disability with substantial healthcare costs, and efficient nonsurgical treatment methods are still needed. Platelet-rich plasma (PRP) injections and exercise therapy are used frequently in clinical practice. Whether PRP or PRP combined with exercise is more effective than exercise alone is unclear. QUESTIONS/PURPOSES: (1) Which treatment relieves knee osteoarthritis pain better: PRP alone, exercise, or PRP combined with exercise? (2) Does PRP alone, exercise, or PRP combined with exercise yield better results in terms of the WOMAC score, performance on the 40-m fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score? METHODS: In this randomized, controlled, three-arm clinical trial, we recruited patients with mild-to-moderate (Kellgren-Lawrence Grade II or III) knee osteoarthritis with a minimum of 3 points on the 11-point numeric rating scale for pain. During the study period, 157 patients with a diagnosis of knee osteoarthritis were screened and 84 eligible volunteers were enrolled in the study. Patients were randomly allocated (1:1:1) into either the exercise group (28), PRP group (28), or PRP + exercise group (28). Follow-up proportions were similar between the groups (exercise: 89% [25], PRP: 86% [24], PRP + exercise: 89% [25]; p = 0.79). All patients were analyzed in an intention-to-treat manner. There were no between-group differences in age, gender, arthritis severity, and baseline clinical scores (pain, WOMAC, functional performance tests, and health-related quality of life). The exercise group underwent a 6-week structured program consisting of 12 supervised individual sessions focused on strengthening and functional exercises. Meanwhile, the PRP group received three weekly injections of fresh, leukocyte-poor PRP. The PRP + exercise group received a combined treatment with both interventions. The primary outcome was knee pain over 24 weeks, measured on an 11-point numeric rating scale for pain (ranging from 0 to 10, where 0 represents no pain and 10 represents the worst pain, with a minimum clinically important difference [MCID] of 2). The secondary outcome measures included the WOMAC index (ranging from 0 to 100, with lower scores indicating a lower level of disability and an MCID of 12), the durations of the 40-meter fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score. For the a priori sample size calculation, we used the numeric rating scale score for pain at 24 weeks as the primary outcome variable. The MCID for the numeric rating scale was deemed to be 2 points, with an estimated standard deviation of 2.4. Based on sample size calculations, a sample of 24 patients per group would provide 80% power to detect an effect of this size between the groups at the significance level of p = 0.05. RESULTS: We found no clinically important differences in improvements in pain-defined as ≥ 2 points of 10-at 24 weeks when comparing exercise alone to PRP alone to PRP + exercise (1.9 ± 0.7 versus 3.8 ± 1.8 versus 1.4 ± 0.6; mean difference between PRP + exercise group and exercise group -0.5 [95% confidence interval -1.2 to 0.4]; p = 0.69). Likewise, we found no differences in WOMAC scores at 24 weeks of follow-up when comparing exercise alone to PRP alone to PRP + exercise (10 ± 9 versus 26 ± 20 versus 7 ± 6; mean difference between PRP + exercise group and exercise group -3 [95% CI -12 to -5]; p = 0.97). There were no differences in any of the other secondary outcome metrics among the PRP + exercise and exercise groups. CONCLUSION: PRP did not improve pain at 24 weeks of follow-up in patients with mild-to-moderate knee osteoarthritis compared with exercise alone. Moreover, exercise alone was clinically superior to PRP alone, considering function and the physical component of health-related quality of life. Despite the additional costs and endeavors related to PRP products, the combination of PRP and exercise did not differ from exercise alone. The results of this randomized controlled trial do not support the use of PRP injections in the treatment of patients diagnosed with mild-to-moderate knee osteoarthritis. Consequently, exercise alone is the recommended treatment for reducing pain and enhancing function throughout this timeframe. LEVEL OF EVIDENCE: Level I, therapeutic study.

Exercise compared to a control condition or other conservative treatment options in patients with Greater Trochanteric Pain Syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To estimate the effectiveness of exercise at end of treatment and long-term follow-up compared to a control condition or other conservative treatments in patients with Greater Trochanteric Pain Syndrome (GTPS). METHODS: Databases were searched September 2021 and updated September 2023. Randomized controlled trials (RCT) comparing exercise interventions for patients with GTPS, to a control condition; corticosteroid injection; shock wave therapy; or other types of exercise programs were included. Risk of bias was assessed using the ROB2 tool. Meta-analyses were performed using a random-effects model. The certainty of the evidence was rated by the GRADE approach. RESULTS: Six RCTs including a total of 733 patients with GTPS were included. Three trials compared exercise to sham exercise or wait-and-see control groups, two trials compared exercise to corticosteroid injection, two trials compared exercise to shockwave therapy, and one trial compared exercise to another type of exercise. Meta-analyses showed that in the long term, exercise slightly reduces hip pain and disease severity, while slightly improving patient-reported physical function and global rating of change compared to a control condition. No serious adverse events were reported. Compared to corticosteroid injection, exercise improves long-term global rating of change. CONCLUSION: The current evidence supports a strong recommendation for exercise as first line treatment in patients clinically diagnosed with GTPS. Compared to corticosteroid injection, exercise is superior in increasing the likelihood that a patient experiences a meaningful global improvement. These results are based on few trials and a moderate number of patients. REGISTRATION: This review was prospectively registered in the PROSPERO database of systematic reviews (ID: CRD42021261380). CONTRIBUTION OF PAPER.

Editorial Commentary: Physical Therapy Alone May Not Successfully Treat Patients With Hip Pain and Large α Angles or Decreased Femoral Anteversion Combined With Femoroacetabular Impingement Syndrome.

Understanding the relation between spinopelvic (lumbopelvic) tilt and femoracetabular impingement syndrome (FAIS) is complex, and determining the optimal patient parameters that lead to successful nonoperative management is vital. Physical therapy (PT) focusing on core and posterior chain strengthening is often successful. PT can change the posterior tilt of the pelvis by 5° to 10°, allowing increased range of motion (ROM) and decreased impingement of the hip. However, PT does not change cam anatomy. Thus, PT alone may not sufficiently increase ROM in patients with cam-type impingement and large α angles or limited femoral anteversion. Pelvic compensation may lead to successful nonoperative management of FAIS, but not in all patients. Large-cam, high-flexion athletes with chronic hip pain should try PT. Yet, while some patients with large cam lesions may improve without surgery if femoral version and/or pelvic tilt ROM can be increased, surgery should not be excessively delayed in patients with poor prognostic factors for nonoperative management.

The Contemporary Management of Temporomandibular Joint Intra-Articular Pain and Dysfunction.

The understanding of the causes of temporomandibular joint pain and dysfunction has evolved over 50 years. Historically, the term internal derangement has been used to describe the abnormal relationship between the articular disc, condyle, and glenoid fossa, which was thought to correlate with patient symptoms. It is now known that the pathophysiology of intra-articular pain and dysfunction (IPD) involves synovitis, capsular impingement, symptomatic disc displacement, or a combination of these. Symptomatic disc displacement should only be considered to be a potential source of IPD after synovitis and capsular impingement have been treated. This philosophy provides the opportunity for most patients with IPD to be initially treated nonsurgically or with minimally invasive procedures such as arthrocentesis or arthroscopy.

Effectiveness and safety of tendon-bone-setting in postpartum women with sacroiliac joint pain: A retrospective multicenter study.

Sacroiliac joint (SIJ) pain leads to abnormal joint loading, and is a key risk factor for joint degeneration. This study aimed to determine the effect of tendon-bone-setting on postpartum women with SIJ pain. Multicenter retrospective review of medical records and electroencephalography reports in 10 academic medical centers. 328 postpartum women with sacroiliac joint pain were divided into 2 groups according to the methods of therapy. Group (A) (n = 203) received acupuncture combined with tendon-bone-setting for twenty days, whereas group (B) (n = 125) received only the same acupuncture for twenty days. The outcome measures were the mean values of numeric pain rating scale (NPRS), present pain intensity (PPI) scale, visual analog scale (VAS) and Japanese orthopedic association (JOA) score to evaluate pain intensity, oswestry disability index (ODI), quebec back pain disability scale (QBPDS), active straight leg raise (ASLR) and back pain function scale (BPFS) to evaluate the functional disability, pressure pain thresholds (PPT) at 5 chosen points in the sacroiliac joint region to assess pain sensitivity. All of them were evaluated before and after treatment. The effectiveness from short to long term, as well as safety was assessed in this study. A comparison of the 2 groups after treatment showed statistically significant increases in the mean values of BPFS, JOA and PPT at the 5 chosen points (P < .05), as well as significant reductions in the scores of QBPDS, ODI, ASLR, NPRS, VAS and PPI (P < .05) in favor of group (B). In addition, after treatment for 2 weeks, the considered effective rate in the group (A) was significantly higher than that in the group (B) (P < .05). Also, the cumulative incidence of pain relief at 24 months in the group (A) was greater compared with the group (B) as determined by Kaplan-Meier analysis (P < .05). Interestingly, none serious adverse event for the participants was reported. Tendon-Bone-Setting is effective and safe in treating sacroiliac joint pain for the postpartum women patients in the short and long terms through decreasing pain sensitivity and intensity, as well as improving functional ability.

Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway.

BACKGROUND: Gout pain seriously affects the quality of patients' life. There is still no effective treatment. The inflammatory response is the main mechanism of gout. Here, we found that ozone can reduce the inflammatory reaction in the joints of gouty mice and relieve gout pain, and we further explore its protective mechanism. METHODS: MSU was used to establish the gouty mice model. Nociception was assessed by Von Frey hairs. Cell signaling assays were performed by western blotting and immunohistochemistry. The mouse leukemia cells of monocyte macrophage line RAW264.7 were cultured to investigate the effects of ozone administration on macrophage. RESULTS: Ozone reduced inflammation, relieved gout pain and improved the paw mean intensity and duty cycle of the gouty mice. Ozone increased the phosphorylation of AMP-activated protein kinase (AMPK), induced suppressor of cytokine signaling 3 (SOCS3) expression and inhibited metallopeptidase 9 (MMP9) expression. In vivo, ozone activated AMPK to induce Gas6 release, and upregulated MerTK/SOCS3 signaling pathway to reduce inflammation in mouse macrophage line RAW264.7. Inhibitors of AMPK and MerTK, respectively abolished the analgesic and anti-inflammatory effects of ozone in vivo and in vitro. Gas6 knockout cancelled the protectively effects of ozone on gout pain and the paw mean intensity and duty cycle of gouty mice. Additionally, the level of Gas6 and protein S in plasma of patients with hyperuricemia was significantly higher than that of healthy contrast group. CONCLUSION: Ozone reduces inflammation and alleviates gout pain by activating AMPK to up-regulate Gas6/MerTK/SOCS3 signaling pathway.