Improvement in gait velocity variability after cerebrospinal fluid elimination and its relationship to clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. METHODS: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG-CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini-Mental State Examination and the Frontal Assessment Battery. RESULTS: The TUG, TUG-CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre-CSF elimination results showed that the TUG-CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini-Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini-Mental State Examination results were significant predictors of the TUG-CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG-CV. CONCLUSIONS: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; ••: ••-••.

Role of tear size and tendon degeneration for development of pain in rat models of rotator cuff tear.

BACKGROUND: Rotator cuff tear (RCT) is a frequent etiology of shoulder pain and disability; however, the triggers for the onset and aggravation of pain remain obscure. In this study, we established novel rat RCT models to examine the impact of tear size and tendon degeneration on pain. METHODS: Fifty-five adult male Sprague-Dawley rats were allocated into 4 study groups: large tear (L group, n = 10), small tear (S group, n = 15), small tear with scratching (S+ group n = 15), and sham surgery (Sham group, n = 15). Pain-related behaviors were evaluated by weight distribution of forelimbs during a 5-minute free gait using a dynamic weight-bearing apparatus at 2, 4, 6, and 8 weeks. Calcitonin gene-related peptide (CGRP) expressions in ipsilateral dorsal root ganglion (DRG) neurons of C4, C5, and C6 were evaluated at 4 and 8 weeks. The area of scar tissues around the torn tendon, infiltration of inflammatory cells, and severity of tendon degeneration (modified Bonar score) were histologically assessed at 4 and 8 weeks. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to evaluate the levels of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) expression in torn tendons and surrounding tissues at 4 weeks. RESULTS: The weight distribution ratio (ipsilateral and contralateral side) was significantly decreased in the L and S+ group compared with its baseline and Sham group (P < .05), but the S group showed no significant difference compared with the Sham. The ratio of CGRP-immunoreactive neurons in the DRGs was significantly higher in the L and S+ groups than in the S and Sham groups. The histologic assessment indicated that scar tissue formation was more extensive in the L group than in the S and S+ groups. Still, there was no significant difference between the S and S+ groups. The modified Bonar score was considerably higher in the S+ group than in the S group. Furthermore, ELISA analysis demonstrated no significant disparity in COX-2 levels between the groups; however, NGF levels were substantially higher in the S+ group than in the S and Sham groups. CONCLUSION: The present study provides compelling evidence that large RCT is strongly associated with heightened pain severity in a rat model. Nevertheless, even a small tear can significantly aggravate pain when the torn tendon is degenerated. CGRP upregulation driven by peripheral NGF possibly played a pivotal role in the genesis and exacerbation of pain in small RCT.

Association between infrapatellar fat pad ultrasound elasticity and anterior knee pain in patients with knee osteoarthritis.

This study investigates whether infrapatellar fat pad (IPFP) elasticity is associated with anterior knee pain in patients with knee osteoarthritis (KOA). The IPFP elasticity of 97 patients with KOA (Kellgren and Lawrence [KL] grades of the femorotibial and patellofemoral joints ≥ 2 and ≤ 2, respectively), aged 46-86 years, was evaluated via shear wave speed using ultrasound elastography. The patients were divided into two groups according to the presence or absence of anterior knee pain. Univariate analyses were used to compare patient age, sex, femorotibial KL grade, magnetic resonance imaging findings (Hoffa, effusion synovitis, bone marrow lesion scores, and IPFP size), and IPFP elasticity between the groups. Multivariate logistic regression analyses were subsequently performed using selected explanatory variables. IPFP elasticity was found to be associated with anterior knee pain in the univariate (p = 0.007) and multivariate (odds ratio: 61.12, 95% CI 1.95-1920.66; p = 0.019) analyses. Anterior knee pain is strongly associated with stiffer IPFPs regardless of the femorotibial KL grade, suggesting that ultrasound elastography is useful for the diagnosis of painful IPFP in patients with KOA.

Assessment of multiple domains of pain following BNT162b2 mRNA COVID-19 vaccination.

Pain at the injection site is the most frequent reaction among COVID-19 vaccine recipients, but its characteristics were not fully described yet. The purpose of this study was to investigate multiple domains of pain following BNT162b2 mRNA vaccination. We included 107 subjects undergoing primary shot of the vaccination twice into deltoid muscle with a 3-week interval. They completed 6 sessions of pain assessments, one before the first and second dose (1-0, 2-0), and 1st/7th day after the first and second dose (1-1/1-7, 2-1/2-7). Pain visual analog scale (VAS), pain distribution, and pressure pain threshold (PPT) on deltoid muscle were evaluated in each session. The mean VAS (at rest/shoulder motion) was 6.0/27.6 mm at 1-1, and 12.8/34.0 mm at 2-1. Approximately, 90% of recipients showed localized pain within the upper arm. Percentage change of PPTs at 1-1 and 2-1 was bilaterally (ipsilateral/contralateral) decreased to 87.4/89.4% and 80.6/91.0%, which was recovered to the baseline level at 1-7 and 2-7. Temporary, mild-to-moderate intensity, localized distribution, concomitant with bilateral mechanical hyperalgesia on the deltoid muscle, were typical pain characteristics following this vaccination. These findings provide a rationale that will be informative for future recipients. J. Med. Invest. 70 : 355-360, August, 2023.

Association Between Power Doppler Ultrasound Signals and Chronic Pain After Total Knee Arthroplasty: A Cross-Sectional Explorative Study.

Purpose: Some patients experience chronic postsurgical pain (CPSP) after total knee arthroplasty (TKA) despite the absence of clinical or radiographic abnormalities. Postoperative synovitis as a cause of CPSP after TKA has received limited research attention. This study aimed to investigate the relationship between synovitis after TKA and CPSP. Patients and Methods: A total of 111 knees of 85 patients, with at least 1-year post-TKA follow-up, were assessed retrospectively and cross-sectionally. Power Doppler (PD) ultrasonography was used to detect the synovial hypervascularity associated with synovitis. The knee joint was divided into 15 areas, and PD signals were graded semi-quantitatively (0-3) in each area, the sum of which was defined as the total PD score. Clinical information regarding CPSP, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscales, was recorded. The relationship between pain and PD ultrasonography findings was accessed. Patients were divided into two groups (CPSP+ and CPSP- groups) based on pain severity. Clinical information, including PD ultrasonography findings and other possible causes, was compared between the groups. Results: The WOMAC pain subscale was significantly correlated with the total PD score and maximum PD grade (r=0.3977, p<0.0001; r=0.2797, p=0.0029; respectively). The CPSP+ group had a significantly higher maximum PD grade and total PD score than the CPSP- group (median [interquartile range]: 2 [1, 2] vs 1 [1, 2], p=0.0001; 6 [2, 11] vs 2 [1, 4], p=0.0002; respectively). Multiple and logistic regression analyses showed that the total PD score was an independent factor for the WOMAC pain subscale (ß=0.3822, 95% confidence interval [CI]=0.1460, 0.6184, p=0.00176) and CPSP (odds ratio=1.19, 95% CI=1.01, 1.41, p=0.0424). Conclusion: This study indicated a possible association between the total PD score and chronic pain after TKA; however, further studies are needed to corroborate these findings.

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.

The effect of postmenopausal osteoporosis on subchondral bone pathology in a rat model of knee osteoarthritis.

This study aimed to investigate the additional effect of ovariectomy-induced osteoporosis (OP) on the pathology of knee osteoarthritis (OA) in a rat meniscectomized model, particularly focusing on subchondral bone changes and pain behaviour. Rats were divided into four groups, sham, OP, OA, OP plus OA, and assessed for histology, osteoclast activity, subchondral bone microstructure, and pain-related behaviour. Rats with OP plus OA had significantly increased calcified cartilage and subchondral bone damage scores, increased densities of subchondral osteoclasts in the weight-bearing area, and more porous subchondral trabecular bone compared with rats with OA. Loss of tidemark integrity was observed most frequently in rats with OP plus OA. The density of subchondral osteoclasts correlated with the calcified cartilage and subchondral bone damage score in rats with OA (OA and OP plus OA). No significant differences in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) expression ratio in subchondral bone and pain-related behavioural tests were observed between rats with OA and rats with OP plus OA. In rats with OA, coexisting OP potentially aggravated OA pathology mainly in calcified cartilage and subchondral trabecular bone by increasing subchondral osteoclast activity.

A Novel Rat Model to Study Postsurgical Pain After Joint Replacement Surgery.

Purpose: The mechanisms underlying chronic postsurgical pain after joint replacement (JR) are complex, and it has been suggested that chronic postsurgical pain can develop as a result of inadequate acute pain management. Few studies have addressed acute pain after JR using specific animal models. This study aimed to develop a novel JR model focused on postsurgical pain assessment and the time course of pain recovery. Materials and Methods: Rats were allocated to the following three groups: sham (joint exposure), joint destruction (JD; resection of the femoral head), and JR (femoral head replacement using an originally developed implant). The time course of postsurgical pain behavior was measured using a dynamic weight-bearing apparatus, along with radiological assessments. The expression of calcitonin gene-related peptide-immunoreactive (CGRP-IR) neurons in the dorsal root ganglion (DRG) was evaluated by immunohistochemistry on days 28 and 42. Results: The ratio of weight-bearing distribution in the JR group gradually recovered from day 14 and reached the same level as that in the sham group on day 42, which was significantly greater than that in the JD group after day 7 (p<0.05). Radiologically, no significant issues were found, except for transient central migration of the implant in the JR group. The percentage of CGRP-IR DRG neurons in the JR group was significantly lower than that in the JD group on day 28 (mean, 37.4 vs 58.1%, p<0.05) and day 42 (mean, 32.3 vs 50.0%, p<0.05). Conclusion: Our novel JR model presented acute postsurgical pain behavior that was successfully recovered to the baseline level at day 42 after surgery. Difference of the pain manifestation between the JR and JD groups could be supported by the expression of CGRP-IR in DRG neurons. This model is the first step toward understanding detailed mechanisms of post-JR pain.

Detection of altered pain facilitatory and inhibitory mechanisms in patients with knee osteoarthritis by using a simple bedside tool kit (QuantiPain).

Purpose: Altered pain facilitatory and inhibitory mechanisms have been recognized as an important manifestation in patients with chronic pain, and quantitative sensory testing (QST) can act as a proxy for this process. We have recently developed a simple bedside QST tool kit (QuantiPain) for more clinical use. The purpose of this study was to investigate its test-retest reliability and to evaluate its validity compared with the laboratory-based QST protocols in patients with knee osteoarthritis (OA). Methods: QuantiPain consists of 3 items: "pressure algometer" (for pressure pain thresholds [PPTs]), "pinprick" (for temporal summation of pain [TSP]), and "conditioning clamp" (for conditioned pain modulation [CPM]). In experiment-A, intrarater and interrater test-retest reliabilities were investigated in 21 young healthy subjects by using interclass correlation coefficient (ICC). In experiment-B, 40 unilateral painful patients with OA and 40 age-matched, healthy control subjects were included to compare the bedside tool kit against the computerized pressure algometry. Results: In experiment-A, excellent to moderate intrarater and interrater reliabilities were achieved in PPT and TSP (ICC: 0.60-0.92) while the agreements of CPM were good to poor (ICC: 0.37-0.80). In experiment-B, localized and widespread decrease of PPT, facilitated TSP, and impaired CPM was found by using the bedside tool kit in patients with OA compared with controls (P < 0.05). The data were significantly correlated with the established laboratory-based tools (R = 0.281-0.848, P < 0.05). Conclusion: QuantiPain demonstrated acceptable test-retest reliability and assessment validity with the sensitivity to separate patients with painful OA from controls, which has a potential to create more practical approach for quantifying altered pain mechanisms in clinical settings.

Increased Calcitonin Gene-Related Peptide Expression in DRG and Nerve Fibers Proliferation Caused by Nonunion Fracture in Rats.

PURPOSE: Nonunion bone fracture can be a cause of persistent pain, but the pathophysiology remains largely unknown. The objective of this study was to identify how nonunion affect persistent pain after fracture. Specifically, we evaluated the association of neuropeptide change in dorsal root ganglia (DRG) and nerve proliferation at fracture sites with pain. METHODS: Rat union and nonunion fracture models were created. A piece of latex glove was placed at the fracture site to create a nonunion model. At 6 weeks after surgery, bone healing was assessed using radiography. In addition, the presence of calcitonin gene-related peptide-immunoreactive (CGRP-IR) DRG at the level of L3 and anti-growth associated protein 43-immunoreactive (GAP43-IR) nerve fibers in the scar tissue between the bone fragments were evaluated. Pain-related behavior was assessed using forced treadmill running. RESULTS: In radiological images at 6 weeks after surgery, callus formation was formed continuously between bone fragments in the union models. On the one hand, a clear gap was detected between fragments in nonunion models. The percentage of CGRP-IR DRG cells and the density of GAP43-IR nerve fibers in the scar tissue between the bone fragments in nonunion models was significantly higher than that in union models (p < 0.05). An increase in inflammatory cell infiltrate was observed in scar tissues in the nonunion models. During forced treadmill running, rats in the union model could run significantly longer than those in the nonunion models. CONCLUSION: Increased CGRP expression in DRG cells and abnormal nerve proliferation secondary to prolonged inflammation could lead to persistent pain after bone fracture. In clinical practice, early achievement of bone union may minimize the development of persistent pain after fractures.

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.

Efficacy and safety of magnetic resonance-guided focused ultrasound treatment for refractory chronic pain of medial knee osteoarthritis.

OBJECTIVE: To elucidate the efficacy and safety of MRgFUS in the treatment for refractory pain derived from medial knee OA. METHODS: Twenty patients with medial knee OA eligible for total knee arthroplasty were included in this prospective, non-controlled study (UMIN000010193). MRgFUS treatment was provided at the site of most severe tenderness around the medial femorotibial joint of each patient under real-time monitoring of temperature. The goal temperature of the targeted bone surface was 55 °C. Numerical rating scale (NRS) worst pain scores, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores, EuroQol 5 dimensions index (EQ-5D) scores and pressure pain threshold (PPT) were evaluated before treatment (baseline) and at 1 week and 1, 3, 6, and 12 months post-treatment, respectively. Complications and adverse events were also assessed clinically and radiographically. RESULTS: Treatment response (a 50% or greater decrease in NRS score) was seen in 14 patients (14/19, 73.7%) at 12 months post-treatment. Mean NRS score rapidly decreased at 1 month after treatment and continued to decline through the following 12 months. At final follow-up, mean NRS score was 3.2 ± 1.9, significantly lower than at baseline (p = 0.0013). Mean WOMAC and EQ-5D scores also improved significantly from 1 month after treatment. Fifteen patients showed significant sustained increases in PPTs at the sites of most severe tenderness. No serious adverse events were observed during and after treatment. CONCLUSIONS: MRgFUS treatments were effective not only for managing refractory pain, but also for improving physical functions without adverse events in elderly patients with medial knee OA.

Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear.

PURPOSE: Degenerative long head of biceps tendon (LHBT) has been recognized as a notable pain source in patients with rotator cuff tear (RCT). Tenotomy or tenodesis of LHBT is frequently indicated together with arthroscopic rotator cuff repair (ARCR) aiming for complete pain relief; however, it has not been fully investigated whether resected LHBT is really a source of pain. The purpose of this study was to investigate expression levels of pain-associated mediators in LHBT and its association with preoperative pain profiles. METHODS: Twenty-seven RCT patients who underwent ARCR with LHBT resection were included. Each LHBT was resected due to its abnormal arthroscopic findings including tenosynovitis, hypertrophy, and partial tear. Worst macroscopic lesion of the LHBT was obtained, and expression levels of substance P (SP) and nerve growth factor (NGF) were evaluated using enzyme-linked immunosorbent assay (ELISA). Ten healthy knee flexor tendons were analyzed as non-degenerative samples. Preoperatively, subjective shoulder pain VAS and pain duration were investigated. Conventional LHBT pain provocation tests (Speed, Yergason, O'Brien) were performed. Pressure pain threshold (PPT) of bilateral LHBT on the groove was recorded. RESULTS: Levels of SP and NGF expression were significantly higher compared with non-degenerative tendons (P<0.01). Shoulder pain VAS and pain duration were not directly associated with SP and NGF expression level. Patients with positive O'Brien test expressed greater SP than negative patients (P=0.001). Significant negative correlation between the PPT ratio (ipsilateral/contralateral) and SP expression level was observed (r=-0.453, P=0.034). CONCLUSION: Greater expression of SP and NGF in degenerative LHBT supported our hypothesis that it would be a pain source in RCT patients. SP was likely to be expressed highly in patients with localized pressure pain hypersensitivity and positive O'Brien test (ie, altered mechanistic pain profile of LHBT), which may help when considering simultaneous LHBT resection during ARCR. CLINICAL REGISTRATION: UMIN000023943.

Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.

Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1ß, IL-6, TNF-α, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.

Comparison of Predisposing Factors Between Pain on Walking and Pain at Rest in Patients with Knee Osteoarthritis.

PURPOSE: Patients with knee osteoarthritis (OA) complain of various types of pain, divided into two main categories: pain on movement and pain at rest. A thorough understanding of pain is essential for managing knee OA; however, few studies have investigated the mechanisms underlying the two different types of pain. This study aimed to clarify the predisposing factors for pain in patients with knee OA with a focus on differences between pain on walking and pain at rest. PATIENTS AND METHODS: This study involved 93 patients, aged 44-90 years, with knee OA, including 74 women. We assessed demographic variables (sex, age, body mass index [BMI], side), visual analogue scale (VAS) score on walking, VAS score at rest, Kellgren and Lawrence (KL) grade on radiograph, synovitis score and bone marrow lesion (BML) score on magnetic resonance imaging, and pressure pain threshold (PPT), and used univariate and multiple regression analyses to investigate factors predisposing patients to pain at rest or pain on walking. RESULTS: In the univariate analyses, we found significant correlations between VAS score on walking and BMI (r=0.31, p<0.01), KL grade (r=0.40, p<0.01), synovitis score (r=0.26, p=0.01), and BML score (r=0.36, p<0.01), whereas VAS score at rest correlated with PPT (r=-0.23, p=0.02) and BMI (r= 0.26, p=0.01). Multiple regression analysis showed that significant explanatory factors for VAS score on walking were BMI (ß=0.22, p=0.03) and KL grade (ß=0.27, p=0.03). By contrast, PPT was the only significant explanatory factor for VAS score at rest (ß=-0.27, p=0.01). CONCLUSION: Predisposing factors were significantly different between pain on walking and pain at rest, indicating that different pain mechanisms exist in the two types of pain. Pain on walking was more strongly associated with mechanical and structural factors, while pain at rest was associated with mechanical hyperalgesia of the knee. CLINICAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registration number; 000041190.

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.

Effects of MRgFUS Treatment on Musculoskeletal Pain: Comparison between Bone Metastasis and Chronic Knee/Lumbar Osteoarthritis.

Local bone denervation by magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool for alleviation of pain in patients with painful bone metastasis (BM). Considering the underlying mechanism of pain alleviation, MRgFUS might be effective for various bone and joint diseases associated with local tenderness. This study was conducted to clarify the therapeutic effect of focused ultrasound in patients with various painful bone and joint diseases that are associated with local tenderness. Ten patients with BM, 11 patients with lumbar facet joint osteoarthritis (L-OA), and 19 patients with knee osteoarthritis (K-OA) were included. MRgFUS treatment was applied to the bone surface with real-time temperature monitoring at the target sites. Pain intensity was assessed using a 100 mm numerical rating scale (NRS) at various time points. Pressure pain threshold (PPT) was evaluated on the sonication area and control sites. Compared to baseline, the pain NRS scores significantly decreased in all groups 1 month after treatment, and PPT at the treated sites significantly increased in all groups 3 months after treatment. The percentage of patients who showed a ≥ 50% decrease in pain NRS scores at 1 month after treatment was 80% in BM, 64% in L-OA, and 78% in K-OA groups. PPTs were significantly higher after treatment at all evaluation time points. This study indicated that MRgFUS is effective in reducing pressure pain at the site of most severe tenderness in patients with painful bone and joint diseases. Treatment response was comparable between patients with BM, L-OA, and K-OA.