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.

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.

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.

Additional benefit of local infiltration of analgesia to femoral nerve block in total knee arthroplasty: double-blind randomized control study.

PURPOSE: Multimodal analgesia has become an important concept in current pain management following total knee arthroplasty (TKA). However, controversy remains over what is the most accepted combination. In this study, the additional benefits of local infiltration of analgesia to femoral nerve block were evaluated. METHODS: Forty patients were randomly allocated into a combined local infiltration of analgesia and femoral nerve block or femoral nerve block alone group. In the former, analgesic drugs consisting of ropivacaine and dexamethasone were injected into the peri-articular tissues, while the same amount of saline was injected into the femoral nerve block group. The primary outcome measure was the total amount of fentanyl consumption by the patient-controlled analgesia pump during the 48-h post-operative period. RESULTS: A combination of local infiltration of analgesia and femoral nerve block had less total fentanyl consumption and a larger knee ROM at post-operative day 2 than femoral nerve block alone (p < 0.05). C-reactive protein levels in the combined treatment group were significantly lower than the femoral nerve block group at post-operative day 3 (p < 0.01). There was no difference between the two groups, post-operatively, on the visual analogue scale for pain at rest or while walking, quadriceps strength, timed up and go test, circumference of thigh, Knee Society Score, and Western Ontario and McMaster Universities Osteoarthritis Index. CONCLUSION: The addition of local infiltration of analgesia to femoral nerve block promoted post-operative pain relief and the recovery of knee ROM in the early post-operative period. This combination is an effective method for post-operative pain management after TKA. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.

Less deep vein thrombosis due to transcutaneous fibular nerve stimulation in total knee arthroplasty: a randomized controlled trial.

PURPOSE: It has been known for years that deep vein thrombi (DVT) start to develop during total joint arthroplasty. Previously, we reported effective prevention of venous stasis by transcutaneous electrical nerve stimulation (TENS). It is hypothesized that TENS might be a thromboprophylactic tool for the limb undergoing surgery. The purpose of this study is to clarify the clinical efficacy and safety of TENS in patients during total knee arthroplasty (TKA). METHODS: Ninety patients undergoing primary TKA were involved and randomly allocated to the TENS or control group. In the TENS group, electrical stimulation of the common fibular nerve, which produced a brisk dorsiflexion of the ankle, was performed for the operated leg during surgery. In the control group, no electrical stimulation was applied. Serum D-dimer and soluble fibrin monomer complex (SFMC) levels were measured before surgery, immediately after surgery, and post-operative day (POD) 1. Ultrasonography was performed on POD 1. RESULTS: Immediately after surgery, D-dimer and SFMC levels of each group were significantly lower in the TENS group compared with control (p < 0.05). The incidence of DVT was 11 % (five cases) in the TENS group while 31 % (14 cases) in control (p = 0.02). There were no adverse effects related to TENS. CONCLUSIONS: TENS during TKA showed significant effects on preventing DVT. Sustaining muscle pump activation during surgery prevented not only venous stasis, but also hypercoagulability of blood. Intraoperative TENS is a safe and novel strategy against early post-operative thromboembolism, which is difficult to be completed through existing prophylaxis after total joint arthroplasty. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.

Less invasive modified Spitzy shelf procedure for patients with dysplasia of the hip.

The shelf procedure for developmental dysplasia of the hip (DDH) is a simpler technique compared with periarticular acetabular osteotomies. However, the most commonly used approach involves the exposure of a large section of the outer iliac surface via a long skin incision and is relatively invasive. We have developed a mini one-incision technique for shelf procedure using bioabsorbable material, based on a modified Spitzy method. In the present report, we describe this procedure and outcomes. For the procedure, the patients are positioned in the lateral position and a 6-8-cm skin incision is made. The interval between the gluteus medius and the tensor fascia lata is developed without any muscle splitting. Thereafter, image intensification is used for accurate positioning of a slot for the new shelf, and a bone graft for the new shelf is obtained from the internal cortex of the iliac wing. The patient is then positioned with the hip in flexion; through the same sliding skin incision, the bone graft is impacted into the slot, and bioabsorbable screws or plates are implanted to cover and stabilise the new shelf. Cancellous bone chips are packed into the triangular space surrounded by the outer iliac surface, the new shelf, and the bioabsorbable screws or plate. We performed this procedure in 9 patients (12 hips). No progression of osteoarthritis was observed during the follow-up period (mean 28 months). The advantages of this procedure include the small, single, skin incision and minimal removal of the gluteus medius from the outer iliac surface. Based on our results, we believe that this procedure could be effective for the treatment of DDH.

Effects of two different intensities of transcutaneous electrical nerve stimulation on pain thresholds of contralateral muscles in healthy subjects.

[Purpose] This study aimed to investigate the differential effects of high-intensity and low-intensity transcutaneous electrical nerve stimulation on the contralateral side on the pain threshold in healthy subjects. [Subjects and Methods] Twenty-five healthy adults, volunteers received two intensity levels (motor-level, 1.5 times the muscle motor threshold; sensory-level, sensory threshold of the common peroneal nerve), for 30 s on separate days. Pressure pain threshold was recorded on the contralateral tibialis anterior and deltoid muscle before, during, and after stimulation. [Results] Motor-level stimulation significantly increased the pressure pain threshold at both muscle sites, while effects of sensory-level stimulation on pressure pain thresholds were significant only at the deltoid site. The percent change in pressure pain thresholds at both sites was significantly higher during motor-level stimulation. [Conclusion] Motor-level stimulation, applied unilaterally to one leg, produced immediate contralateral diffuse and segmental analgesic effects. This may be of therapeutic benefit in patients for whom transcutaneous electrical nerve stimulation cannot be directly used at the painful site.

The dorsal pedis artery as a new distal landmark for extramedullary tibial alignment in total knee arthroplasty.

PURPOSE: It is better to use multiple anatomical landmarks to reduce errors in component alignment in total knee arthroplasty. Therefore, it is worthwhile to find a new landmark that can be used as an addition to conventional ones. Herein, we assessed the dorsal pedis artery as a new distal landmark for extramedullary tibial alignment. METHODS: Fifty-two ankles in patients undergoing total knee arthroplasty and 10 ankles in normal controls were included. Color Doppler ultrasonography was used to locate the dorsal pedis artery at the level of the ankle joint. Conventional landmarks, including the tibialis anterior tendon, the extensor hallucis longus tendon, the extensor digitorum longus tendon, and the malleolar centre, were also located on ultrasound images. The distances between the ankle centre and each landmark were measured and compared. RESULTS: The dorsal pedis artery was absent in 2 patients and impalpable but visible with ultrasonography in other 2 patients. The dorsal pedis artery was located anatomically closest to the ankle centre in patients (0.4 ± 3.4 mm lateral). Statistical analysis showed that the dorsal pedis artery, the extensor hallucis longus tendon, and the malleolar centre were located significantly closer to the ankle centre comparing with the extensor digitorum longus tendon and the tibialis anterior tendon in both patients and controls (p < 0.001). CONCLUSIONS: As long as the dorsal pedis artery exists, it can be used as an addition to the conventional landmarks in total knee arthroplasty. Using this new landmark will help reduce errors in coronal plane alignment of tibial component. LEVEL OF EVIDENCE: II.

Effects of dexamethasone on local infiltration analgesia in total knee arthroplasty: a randomized controlled trial.

PURPOSE: Intraoperative local infiltration analgesia has gained increasing popularity in joint replacement surgery. Because there is considerable variation among drug combinations, analgesic effects of each drug are not well understood. The purpose of this study was to clarify the efficacy of the addition of steroid to local anaesthetics in local infiltration analgesia during total knee arthroplasty. METHODS: Forty patients were randomly allocated to the steroid or control group. Patients in the steroid group received peri-articular injection of ropivacaine, dexamethasone and isepamicin, while dexamethasone was omitted from the analgesic mixture in the control group. Primary outcome was pain severity at rest using 100 mm visual analogue scale. RESULTS: Pain severity in the steroid group was lower than control group and there were significant differences between groups at post-operative day 1 and 3. Reduction in post-operative pain was associated with a decrease in serum C-reactive protein and interleukin 6 in drainage fluid. The number of patients who were able to perform straight leg raise within post-operative day 2 was 15/20 in the steroid group, which was significantly higher than the control group 5/20. CONCLUSION: Adding steroid to local anaesthetics in local infiltration analgesia reduced inflammation both locally and systemically, resulting in significant early pain relief and rapid recovery in total knee arthroplasty.

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; 24: 693-699.

MR-guided focused ultrasound for the novel and innovative management of osteoarthritic knee pain.

BACKGROUND: Severe knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy. METHODS: Eight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment. RESULTS: Six patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p < 0.0001). There were no adverse side effects or complications during and after treatment. CONCLUSIONS: These initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA. TRIAL REGISTRATION: Trial Registration: UMIN000010193.

Local infusion analgesia using intra-articular double lumen catheter after total knee arthroplasty: a double blinded randomized control study.

PURPOSE: Although intra-operative local infiltration analgesia has gained increasing popularity in joint replacement surgery, it is not clear whether postoperative local infusion analgesia using an indwelling catheter provides clinically important additional effects. We, therefore, conducted a randomized controlled trial to clarify the efficacy of the originally developed local infusion analgesia technique in total knee arthroplasty. METHODS: Forty patients were randomly allocated to the local infusion analgesia or control group. Patients in the local infusion analgesia group received intermittent bolus intra-articular injection of analgesics consisting of ropivacaine, dexamethasone, and isepamicin until postoperative 48 h. Primary outcome was pain severity at rest using 100-mm visual analogue scale. RESULTS: Pain severity in patients of the local infusion analgesia group was lower than control group, and there were significant differences between groups at POD1 (p = 0.025) and POD3 (p = 0.007). Reduction of postoperative pain was associated with a decrease in C-reactive protein level and earlier achievement of straight leg raise. In addition, postoperative drain volume was reduced in the local infusion analgesia group. CONCLUSION: Although larger studies are needed to examine its safety, the local infusion analgesia alone provided clinically significant analgesic effects and rapid recovery in total knee arthroplasty.

Improving tibial component coronal alignment using clearly defined anatomical structures in total knee arthroplasty.

Several authors recently proposed to use clearly defined anatomical structures for extramedullary tibial alignment in total knee replacement, instead of using the intermalleolar center. The purpose of this study was to evaluate the benefits of using the dorsalis pedis artery and the anterior tibial crest as distal landmarks. Postoperative radiographs in 195 knees (98 in the control and 97 in the landmark group) were evaluated. The mean coronal alignment of the tibial component was 89.7 degrees +/- 2.1 degrees in the control group and 90.0 degrees +/- 1.3 degrees in the landmark group. Although there was no significant difference, the proportion of radiological outliers was significantly reduced in the landmark group compared to the control group (6.2% vs 27.6% in > 2 degrees outliers; p < 0.0001, 1.0% vs 10.2% in > 3 degrees outliers; p = 0.01). In order to achieve accurate coronal alignment of the tibial component, it appears better to use multiple clear anatomical landmarks such as the dorsal pedis artery and the anterior tibial crest rather than using only the intermalleolar center.

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.

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.

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.

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.

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.

Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis.

BACKGROUND: Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease. METHODS: We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. RESULTS: OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. CONCLUSIONS: Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.