Associations of serum leptin levels with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice.

BACKGROUND: The roles of serum leptin in knee joint inflammation are unclear. The objective of this study was to identify any associations of serum leptin level with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice. METHODS: Acute arthritis was induced by intra-articular injection of 2% carrageenan. Three groups (leptin-deficient ob/ob, wild-type (WT) and high-fat diet (HFD)-fed WT) were made. Serum leptin and inflammatory cytokines in the infrapatellar fat pad and synovium were measured before and 24 hr after injection. Affected knee joints were excised for histology 24 hr after injection. RESULTS: The HFD-WT group had significantly higher serum leptin than the ob/ob and WT groups before and after carrageenan injection. The HFD-WT group had significantly higher IL-1? and IL-6 in the infrapatellar fat pad and synovium than ob/ob and WT before injection but significantly lower IL-1?, IL-6 and TNF-? than the ob/ob group at 24 hr. CONCLUSIONS: Hyperleptinemia induced by a HFD is involved in low-grade intra-articular inflammation in nonarthritic knee joints. In contrast, leptin deficiency causes excessive intra-articular inflammation in carrageenan-induced acute arthritis. Leptin alleviates acute arthritis, while chronic hyperleptinemia is involved in low-grade inflammation in normal knee joints. J. Med. Invest. 70 : 54-59, February, 2023.

A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells.

PURPOSE: Mast cells are multifunctional in osteoarthritis (OA), and infiltration of activated mast cells likely contributes to disease severity and progression. However, the detailed mechanisms of action are unclear. The purpose of this study was to elucidate the role of mast cell infiltration in OA at histological level using a new mice model and to investigate pharmacological inhibitory effects of existing mast cell stabilizers in this model. METHODS: Mice were injected intra-articularly with monosodium iodoacetate (MIA 0.5 mg) or PBS on day 0, and PBS, with or without mast cells (MC: 1 × 106 cells) on day 14. They were divided into four groups: OA flare (MIA + MC), OA (MIA + PBS), MC non-OA (PBS + MC), and PBS non-OA (PBS + PBS). In OA flare, the MC stabilizer drug (tranilast: 400 mg/kg/day) or PBS was administered intraperitoneally from days 15 to 21. RESULTS: Histologically, modified Mankin score of the OA flare was significantly higher than that of OA (7.0 [1.8] vs. 3.3 [1.3], P < 0.05), and a larger number of mast cells was observed in OA flare than in OA (34.5 [6.3]/mm2 vs. 27.2 [2.3]/mm2, P < 0.05) on day 22. OA flare also showed acute exacerbation of pain and increased gene expression of pro-inflammatory cytokines and aggrecanase compared with OA. Administration of tranilast to OA flare-up provoked significant improvements in term of histological changes, pain, and gene expression at day 22. CONCLUSION: Our novel model possibly mimics OA flare conditions, which may open a new strategy of disease-modifying treatment for OA, focused on controlling the multiple functions of mast cells.

Promising Effect of Visually-Assisted Motor Imagery Against Arthrogenic Muscle Inhibition - A Human Experimental Pain Study.

PURPOSE: Clinically, arthrogenic muscle inhibition (AMI) has a negative impact on functional recovery in musculoskeletal disorders. One possible technique to relieve AMI is motor imagery, which is widely used in neurological rehabilitation to enhance motor neuron excitability. The purpose of this study was to verify the efficacy of visually-assisted motor imagery against AMI using a human experimental pain model. METHODS: Ten healthy volunteers were included. Experimental ankle pain was induced by hypertonic saline infusion into unilateral Kager's fat pad. Isotonic saline was used as control. Subjects were instructed to imagine while watching a movie in which repetitive motion of their own ankle or fingers was shown. H-reflex normalized by the motor response (H/M ratio) on soleus muscle, maximal voluntary contraction (MVC) force of ankle flexion, and contractile activities of the calf muscles during MVC were recorded at baseline, pre-intervention, post-intervention, and 10 minutes after the pain had subsided. RESULTS: Hypertonic saline produced continuous and constant peri-ankle pain (VAS peak [median]= 6.7 [2.1-8.4] cm) compared to isotonic saline (0 [0-0.8] cm). In response to pain, there were significant decreases in the H/M ratio, MVC and contractile activities (P<0.01), all of which were successfully reversed after the ankle motion imagery. In contrast, no significant changes were observed with the finger motion imagery. CONCLUSION: Visually-assisted motor imagery improved the pain-induced AMI. Motor imagery of the painful joint itself would efficiently work for relieving AMI. This investigation possibly shows the potential of a novel and versatile approach against AMI for patients with musculoskeletal pain.

Chronic postsurgical pain after total knee arthroplasty: A prospective cohort study in Japanese population.

OBJECTIVES: To elucidate the prevalence and risk factors of chronic postsurgical pain (CPSP) after primary total knee arthroplasty (TKA) in Japanese population. METHODS: Consecutive patients undergoing primary TKA in a Japanese tertiary hospital (211 knees) were assessed. CPSP after TKA was defined as moderate to severe pain (VAS >30 mm), either at rest or during walking, one year after surgery. Clinical and radiographic data were compared between CPSP and non-CPSP groups and multivariate logistic regression was used to identify predictors of CPSP. RESULTS: The prevalence of CPSP was 8.8%. CPSP group showed significantly higher preoperative WOMAC subscales (pain, function and stiffness), higher rate of postoperative coronal malalignment (femorotibial angle >178° or <170°) and larger varus angle of tibial component compared with non-CPSP group. Logistic regression analysis revealed that preoperative higher WOMAC pain and postoperative coronal malalignment were independent risk factors of CPSP. In a subgroup analysis of patients with well-aligned TKA, preoperative pain VAS at rest was the only risk factor of CPSP. CONCLUSION: Preoperative severe pain and postoperative coronal malalignment were independent risk factors of CPSP after TKA. Preoperative pain management in patients with severe pain and good coronal alignment after TKA possibly minimize the development of CPSP.

Accuracy of acetabular cup placement using an angle-adjusting alignment guide with laser pointer in total hip arthroplasty.

PURPOSE: To evaluate cup-positioning accuracy in total hip arthroplasty (THA) using a novel angle-adjusting alignment guide with laser pointer and determine whether level of surgical experience affects accuracy of cup placement or not. METHODS: We included 117 hips in 104 patients who underwent THA using the novel guide. We retrospectively reviewed 44 hips in 40 patients who underwent THA before the novel guide was introduced. We compared differences in cup angles between the novel guide group and the conventional guide group as well as the discrepancies in targeted angles between the experienced surgeon group and the inexperienced surgeon group. RESULTS: There were 114/117 hips (97.4%) within the Lewinnek safe zone in the novel guide group and 32/44 hips (72.7%) within the safe zone in the conventional guide group. There were significantly fewer outliers in the novel guide group (p < 0.001). In the experienced surgeon group, the mean absolute errors in inclination and anteversion were 2.0 ± 1.7° and 2.1 ± 2.3°, respectively; which were not significantly different from those in the inexperienced surgeon group (2.3 ± 2.1° and 2.8 ± 2.3°, respectively). CONCLUSION: The novel angle-adjusting alignment guide with laser pointer is a simple tool that provides better accuracy of cup position than that obtained using conventional guides. Accurate cup placement is possible using the novel guide, regardless of surgeons' experience.

Nontraumatic Spondylolisthesis of the Axis with Cervical Kyphosis.

This study aimed at presenting a rare nontraumatic spondylolisthesis of the axis and considering its possible cause. Traumatic spondylolisthesis of the axis, called hangman's fracture, frequently occurs as a high-energy trauma. However, nontraumatic spondylolisthesis of the axis is quite rare, and relevant literature on this condition is scarce. We reported a case of a 49-year-old man who had spondylolisthesis of the axis without experiencing a traumatic episode. Plain radiograph and CT image showed 7.0 mm anterolisthesis of the axis. Both C2 and C3 facet joints positioned asymmetrically, and the unilateral side oriented coronally, which was less resistant to rotational motion. These facet joint abnormalities could cause segmental instability and spondylolisthesis of the axis. Due to the resultant myelopathy, the slip with cord compression was surgically corrected by posterior decompression with instrumented fusion.

Chronological changes in functional cup position at 10 years after total hip arthroplasty.

PURPOSE: This study aims to clarify the chronological changes in functional cup position at a minimum follow-up of 10 years after total hip arthroplasty (THA), and to identify the risk factors influencing a significant difference in functional cup position during the postoperative follow-up period. METHODS: We evaluated the chronological changes in functional cup position at a minimum follow-up of 10 years after THA in 58 patients with unilateral hip osteoarthritis. Radiographic cup position was measured on anteroposterior pelvic radiographs with the patient in the supine position, whereas functional cup position was recorded in the standing position. Radiographs were obtained before, 3 weeks after, and every 1 year after surgery. RESULTS: Functional cup anteversion (F-Ant) increased over time, and was found to have significantly increased at final follow-up compared to that at 3 weeks after surgery (p<0.01). The maximum postoperative change in F-Ant was 17.0° anteriorly; 12 cases (21%) showed a postoperative change in F-Ant by >10° anteriorly. Preoperative posterior pelvic tilt in the standing position and vertebral fractures after THA were significant predictors of increasing functional cup anteversion. CONCLUSIONS: Although chronological changes in functional cup position do occur after THA, their magnitude is relatively low. However, posterior impingement is likely to occur, which may cause edge loading, wear of the polyethylene liner, and anterior dislocation of the hip. We believe that, for the combined anteversion technique, the safe zone should probably be 5°-10° narrower in patients predicted to show considerable changes in functional cup position compared with standard cases.

Recurrence of cervical myelopathy secondary to a strut graft fracture 20 years after anterior decompression and fusion: a case report.

This study reports on a 70-year-old man with recurrent cervical myelopathy 20 years after anterior decompression and fusion of C4-7 using a free vascularised strut graft. The recurrent myelopathy was secondary to a kyphotic deformity of a fractured graft and residual ossification of the posterior longitudinal ligament with stenosis at C3/4. Intraoperative spinal cord-evoked potentials indicated that spinal cord traction secondary to progressive kyphosis of the cervical spine after the graft fracture was the cause. The patient underwent laminoplasty at C3 and laminectomy at C4 to decompress the stenosis at C3/4 as well as posterior cervical spinal fusion at C3-7 with pedicle screws and a lateral mass screw and a bone graft to prevent further progression of the kyphosis. At postoperative 18 months, the patient's Japanese Orthopaedic Association score had improved to 14 from 8, and he could walk without support.