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Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.
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Alginatos , Artritis Gotosa , Modelos Animales de Enfermedad , Inflamación , Oligosacáridos , Animales , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/metabolismo , Ratones , Oligosacáridos/farmacología , Alginatos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Artralgia/tratamiento farmacológico , Artralgia/metabolismo , Ácido Úrico/metabolismo , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Articulación del Tobillo/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
BACKGROUND: Ligamentous laxity, cartilage wear, and diffuse synovitis are frequently seen in thumb basal joint arthritis. Although these degenerative changes may be mild for the majority, they have the potential to cause discomfort during movement and compromised hand function. This study assesses the long-term outcomes of arthroscopic debridement, synovectomy, and thermal shrinkage in managing early-stage basal joint arthritis. METHODS: We retrospectively reviewed patients with basal joint arthritis who underwent arthroscopic debridement, synovectomy, and thermal shrinkage between November 2010 and January 2021 by a single surgeon at our medical institute. We assessed functional outcomes, thumb range of motion, perioperative nonsteroidal anti-inflammatory drug (NSAID) use, return to work and satisfaction level. RESULTS: A total of 12 patients (13 hands), with a mean follow-up of 72 months, were included in this study. Significant improvements were observed in pain scores and functional outcomes, along with a reduction in postoperative NSAID use. Patients also reported a relatively quick return to work and a high satisfaction level. CONCLUSION: The study highlights the benefits of arthroscopic intervention, providing a minimally invasive approach with favorable long-term outcomes for patients with symptomatic basal joint arthritis.
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Artroscopía , Desbridamiento , Sinovectomía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Artritis/cirugía , AdultoRESUMEN
BACKGROUND: Ulnar shortening osteotomy (USO) has demonstrated good outcomes for patients with ulnar impaction syndrome. To minimize complications such as non-union, precise osteotomy and firm fixation are warranted. Despite various ulnar shortening systems have been developed, current technology does not meet all needs. A considerable portion of patients could not afford those designated USO systems. To tackle this challenge, our team reported successful results in standardized free-hand predrilled USO technique. However, it is still technical demanding and requires sufficient experience and confidence to excel. Therefore, our team designed an ulnar shortening system based on our free-hand technique principle, using metal additive manufacturing technology. The goal of this study is to describe the development process and report the performance of the system. METHODS: Utilizing metal additive manufacturing technology, our team developed an ulnar shortening system that requires minimal exposure, facilitates precise cutting, and allows for the easy placement of a 3.5 mm dynamic compression plate, available to patients at zero out-of-pocket cost. For performance testing, two surgeons with different levels of experience in ulnar shortening procedures were included: one fellow-trained hand and wrist surgeon and one senior resident. They performed ulnar shortening osteotomy (USO) using both the free-hand technique and the USO system-assisted technique on ulna sawbones, repeating each method three times. The recorded parameters included time-to-complete-osteotomy, total procedure time, chip diameter, shortening length, maximum residual gap, and deviation angle. RESULTS: For the hand and wrist fellow, with the USO system, the time-to-complete osteotomy was significantly reduced. (468.7 ± 63.6 to 260.0 ± 5 s, p < 0.05). Despite the preop goal was shortening 3 mm, the average shortening length was significantly larger in the free-hand group (5 ± 0.1; 3.2 ± 0.2 mm, p < 0.05). Both maximum residual gap and deviation angle reported no statistical difference between the two techniques for the hand surgeon. As for the senior resident, the maximum residual gap was significantly reduced, using the USO system (2.9 ± 0.8; 0.4 ± 0.4 mm, p = 0.02). Between two surgeons, significant larger maximum residual gap and deviation angle were noted on the senior resident doctor, in the free-hand technique group, but not in the USO system group. CONCLUSION: The developed USO system may serve as a valuable tool, aiding in reliable and precise cutting as well as fixation for patients undergoing ulnar shortening osteotomy with a 3.5 mm dynamic compression plate, even for less experienced surgeons. The entire process, from concept generation and sketching to creating the CAD file and final production, serves as a translatable reference for other surgical scenarios.
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Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation. CXCL5 expression was increased in ankle joints of gout arthritis model mice, whereas CXCR2 showed expression in joint-innervating sensory neurons. CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to trigger TRPA1 activation, resulting in hyperexcitability and pain. Neuronal CXCR2 coordinates with neutrophilic CXCR2 to contribute to CXCL5-induced neutrophil chemotaxis via triggering CGRP- and substance P-mediated vasodilation and plasma extravasation. Neuronal Cxcr2 deletion ameliorates joint pain, neutrophil infiltration and gait impairment in model mice. We confirmed CXCR2 expression in human dorsal root ganglion neurons and CXCL5 level upregulation in serum from male patients with gouty arthritis. Our study demonstrates CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and inflammation that expands our knowledge of immunomodulation capability of nociceptive sensory neurons.
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Artritis Gotosa , Animales , Humanos , Masculino , Ratones , Artralgia , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo , Inflamación , Nocicepción , Nociceptores/metabolismo , DolorRESUMEN
Allergic contact dermatitis (ACD) is a common skin disease featured with skin inflammation and a mixed itch/pain sensation. The itch/pain causes the desire to scratch, affecting both physical and psychological aspects of patients. Nevertheless, the mechanisms underlying itch/pain sensation of ACD still remain elusive. Here, we found that oxidative stress and oxidation-related injury were remarkably increased in the inflamed skin of a mouse model of ACD. Reducing oxidative stress significantly attenuated itch/pain-related scratching, allokonesis and skin inflammation. RNA-Sequencing reveals oxidative stress contributes to a series of skin biological processes, including inflammation and immune response. Attenuating oxidative stress reduces overproduction of IL-1ß and IL-33, two critical cytokines involved in inflammation and pain/itch, in the inflamed skin of model mice. Exogenously injecting H2O2 into the neck skin of naïve mice triggered IL-33 overproduction in skin keratinocytes and induced scratching, which was reduced in mice deficient in IL-33 receptor ST2. ACD model mice showed remarkable neutrophil infiltration in the inflamed skin. Blocking neutrophil infiltration reduced oxidative stress and attenuated scratching and skin inflammation. Therefore, our study reveals a critical contribution of neutrophil-derived oxidative stress to skin inflammation and itch/pain-related scratching of ACD model mice via mechanisms involving the triggering of IL-33 overproduction in skin keratinocytes. Targeting skin oxidative stress may represent an effective therapy for ameliorating ACD.
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Dermatitis Alérgica por Contacto , Interleucina-33 , Humanos , Animales , Ratones , Interleucina-33/genética , Citocinas , Peróxido de Hidrógeno/farmacología , Neutrófilos , Piel , Dermatitis Alérgica por Contacto/psicología , Prurito/inducido químicamente , Modelos Animales de Enfermedad , Inflamación , DolorRESUMEN
PURPOSE: Recent biomechanical studies have highlighted the importance of foveal reinsertion when repairing triangular fibrocartilage complex (TFCC) injury with foveal tears. However, clinical studies comparing different repair techniques are scarce. We compared the clinical outcomes of suture anchor repair and rein-type capsular suture in patients with TFCC palmer 1B foveal tears with a minimum of 2-year follow-up. METHODS: This was a single-surgeon, single-center, retrospective, comparative study. We included patients who underwent TFCC repair surgery due to a foveal tear from December 2013 to October 2018 with a minimum follow-up of 24 months. Postoperative Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score, visual analogue scale for pain, wrist range of motion, and grip strength were compared. We also measured the maximal ulnar head displacement with dynamic ultrasound to quantify distal radioulnar joint stability. RESULTS: In total, 103 patients were in the suture anchor group (group A) and 84 patients in the rein-type capsular suture group (group B). The mean follow-up time exceeded three years for both groups. There was a minimal difference regarding QuickDASH score, visual analogue scale for pain, and grip strength ratio between the two groups. The rein-type group had significantly better Modified Mayo Wrist Score. The suture anchor group showed better distal radioulnar joint stability with dynamic ultrasound, but was more limited in ulnar deviation. However, these differences are most likely clinically insignificant. CONCLUSIONS: Both suture anchor repair and rein-type capsular suture yielded satisfactory results for TFCC 1B foveal tear in a minimum of 2-year follow-up. The functional scores were similar, and no major complications or recurrent instability were noted in either group. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective Therapeutic Comparative Investigation IV.
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Fibrocartílago Triangular , Traumatismos de la Muñeca , Humanos , Fibrocartílago Triangular/lesiones , Estudios de Seguimiento , Estudios Retrospectivos , Anclas para Sutura , Articulación de la Muñeca/cirugía , Dolor , Traumatismos de la Muñeca/cirugía , Artroscopía/métodos , Suturas , Técnicas de SuturaRESUMEN
Excessive deposition of monosodium urate (MSU) crystal in the joint results in gout arthritis, which triggers severe pain and affects life quality. Oxidative stress is a pivotal mechanism that contributes to etiology of gout pain and inflammation. Here we investigated whether activating Nrf2, which plays important roles in regulating endogenous antioxidant response, would attenuate gout arthritis via promoting antioxidant signaling in joint tissues. Gout arthritis model was established by intra-articular injection of MSU (500 µg/ankle) into the right ankle joint of mouse. Pharmacologically activating Nrf2 by activator oltipraz (50, 100 or 150 mg/kg, intraperitoneal) at 1 h before and 5, 23, 47 h after model establishment dose-dependently inhibited joint inflammation, mechanical and heat hypersensitivities in model mice. Oltipraz (100 mg/kg) reversed gait impairments without altering locomotor activity and reduced neutrophil infiltrations in ankle joints. In vitro studies revealed oltipraz (25 µM) inhibited MSU-induced ROS production in mouse macrophages and improved mitochondrial bioenergetics impairments caused by MSU. In vivo ROS imaging combined with biochemical assays confirmed the antioxidant effects of oltipraz on model mice. Nrf2 activation inhibited pro-inflammatory cytokine overproduction in ankle joint and attenuated the overexpression and enhancement in TRPV1 channel in DRG neurons innervating hind limb. Therapeutic effects of oltipraz were abolished by inhibiting Nrf2 or in Nrf2 knockout mice. These results suggest pharmacologically activating Nrf2 alleviates gout pain, gait impairments, inflammation and peripheral sensitization via Nrf2-dependent antioxidant mechanism. Targeting Nrf2 may represent a novel treatment option for gout arthritis.
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Artritis Gotosa , Gota , Ratones , Animales , Antioxidantes/uso terapéutico , Gota/inducido químicamente , Gota/complicaciones , Factor 2 Relacionado con NF-E2 , Ácido Úrico/efectos adversos , Especies Reactivas de Oxígeno , Artritis Gotosa/tratamiento farmacológico , Inflamación/inducido químicamente , Dolor/tratamiento farmacológicoRESUMEN
OBJECTIVE: K-wire arthrodesis methods are commonly used during arthrodesis of the finger distal interphalangeal (DIP) or thumb interphalangeal (IP) joints. Here we propose an advantageous approach involving dual parallel intramedullary K-wires with the K-wire tips cut to bury underneath the skin. METHODS: From January 2017 to December 2021, 35 patients (43 joints) underwent finger DIP or thumb IP joint arthrodesis using this method. Radiographic outcomes were evaluated, while functional outcomes were assessed using the visual analogue scale (VAS) for pain and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Patients with at least 1 year follow-up were analyzed. The preoperative and postoperative functional results were analyzed using the paired t-test. RESULTS: Arthrodesis union was achieved in 41/43 joints (95.3%). We treated 10 thumb IP joints and 33 finger DIP joints, for which the underlying cause was osteoarthritis and trauma in 37 and six digits, respectively. The average time of K-wire removal was 8.9 (range, 7-10) weeks after surgery. Twenty-four patients (27 joints; 22 women, two men) had at least 1 year follow-up (mean 15.9; range, 12.5-40.8) months. For patients with bone healing, the VAS score improved from 6.6 (range, 5-8) to 0.6 (range, 0-1) (p < 0.001), and the QuickDASH score improved from 57.9 (range, 31.8-77.3) to 14.7 (range, 6.8-20.5) (p < 0.001) at final follow-up. Both of the two failure cases were in the thumb. There were no other complications. CONCLUSIONS: This technique is simple and cost-effective and achieves a good union rate. The advantages include the ability to choose variable K-wire sizes according to the size of the medullary canal and the ease of postoperative care.
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Osteoartritis , Pulgar , Masculino , Humanos , Femenino , Pulgar/cirugía , Dedos , Hilos Ortopédicos , Osteoartritis/cirugía , Artrodesis/métodosRESUMEN
BACKGROUND: The ideal scenario for ulnar nerve repair is primary end-to-end neurorrhaphy in a tension-free environment. However, this could be complicated by soft tissue loss, scarring, and neuroma formation in a delayed injury, creating a nerve defect. With a wrist-level nerve defect, a flexion position can help shorten the nerve gap; however, maintaining the position can be challenging intraoperatively and postoperatively. METHODS: Previously, we proposed our method of using a 1.6-mm K wire for radius-lunate-capitate pinning of the wrist in flexion to minimize the nerve gap, thereby facilitating neuroma excision and end-to-end neurorrhaphy in delayed ulnar nerve injury. In this study, we elaborate our method and present our case series. RESULTS: From October 2018 to July 2020, five patients (mean age: 48.2 years; mean delay from injury to surgery: 84.6 days; mean follow-up: 17.5 months) were retrospectively reviewed. The mean flexion fixation angle was 52°, and the K wire was removed at an average of 5.1 weeks postoperatively. All patients were followed up for a minimum of 12 months. All patients achieved M4 and S3 or S3+ neurologically (according to the criteria of the Nerve Injuries Committee of the British Medical Research Council). The mean disabilities arm, shoulder, and hand score was 14.1. The mean grasp and pinch strengths were, respectively, 76.8% and 63.6% of the contralateral hand. All wrist range of motion returned to normal within 12 weeks. No complications were noted intraoperatively or postoperatively. CONCLUSION: Our study showed that radiocarpal pinning of the wrist in flexion was safe and convenient to minimize the nerve gap and to facilitate end-to-end neurorrhaphy in limited-sized wrist-level ulnar nerve defects.
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Neuroma , Traumatismos de la Muñeca , Humanos , Persona de Mediana Edad , Muñeca , Nervio Cubital/lesiones , Nervio Cubital/cirugía , Estudios Retrospectivos , Articulación de la Muñeca/cirugía , Neuroma/complicaciones , Rango del Movimiento Articular/fisiología , Resultado del Tratamiento , Traumatismos de la Muñeca/complicaciones , Traumatismos de la Muñeca/cirugíaRESUMEN
Various surgical techniques have been described for the fixation of displaced unicondylar fractures of the proximal phalanx, with K-wire and interfragmentary screws being the most commonly used. Although open reduction with joint exposure can provide direct visualization and allow for anatomic reduction, its potential drawbacks, such as joint stiffness and loss of range of motion, are of significant concern. We introduced a novel fixation technique for displaced unicondylar fractures of the proximal phalanx using antegrade intramedullary pinning and transfixation of the proximal interphalangeal joint, which is simple, effective, and does not require open reduction.
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Fijación Intramedular de Fracturas , Fracturas Óseas , Humanos , Fracturas Óseas/cirugía , Fijación Intramedular de Fracturas/métodos , Fijación Interna de Fracturas/métodos , Hilos Ortopédicos , Rango del Movimiento ArticularRESUMEN
BACKGROUND: Gout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain. METHODS: Monosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca2+ imaging and behavioral assays were applied. RESULTS: Model mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA's inhibitory effect on NLRP3 inflammasome and further reversed EA's anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca2+ imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout. CONCLUSIONS: Our results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.
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Pain is a cardinal feature of many diseases. Chronic pain poses heavy burdens to the suffering patients, both physically and mentally. However, current mainstream medications for chronic pain, including opioids, antidepressants and non-steroid anti-inflammatory drugs are sometimes inefficient for chronic pain management and may cause side effects that limit long term usage. IL-33 belongs to IL-1 cytokine family and it exerts biological activities through binding to its specific receptor ST2. IL-33/ST2 signaling is very important in both innate and adaptive immunity. Emerging evidence indicates IL-33/ST2 signaling regulates pain in both immune and somatosensory systems through promoting neuro-immune or neuron-glia crosstalk, neuroinflammation and neuronal hyperexcitability. Some very latest studies indicate a vital part of IL-33/ST2 in mediating chronic itch. This work aims to overview the existing knowledge regarding the mechanisms of IL-33/ST2 involvement in pain and itch conditions, considering their potential similarities. We also summarized some key findings obtained from clinical studies. The targeting of IL-33/ST2 signaling holds promise for the development of novel therapeutic modalities in the management of pain and itch.
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Dolor Crónico , Interleucina-33 , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Transducción de Señal/fisiología , Citocinas/metabolismoRESUMEN
Introduction: Lateral ankle sprain (LAS) is a very common type of joint injury. It occurred with high incidence among general population and especially among individuals participating sports and outdoor activities. A certain proportion of individuals who once developed LAS may suffer persistent ankle pain that affects daily activities. However, the mechanisms underlying LAS-induced pain still remained largely unknown. Methods: We established a LAS mouse model and systematically evaluated the pain-related behaviors in this mouse model. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. Immunostaining was used to study glial cell and neuron activation in ipsilateral spinal cord dorsal horn (SCDH) of LAS model mice. Ibuprofen was used to treat LAS model mice. Results: The LAS model mice developed obvious signs of mechanical and heat hypersensitivities as well as gait impairments in ipsilateral hind paws. Besides, LAS model mice developed signs of pain-related emotional disorder, including pain-induced aversion. By RNA-Seq, we were able to identify certain differentially expressed genes and signaling pathways that might contribute to pain mechanisms of LAS mouse model. In addition, LAS model mice showed increased c-Fos and p-ERK immunoreactivity as well as astrocyte and microglia overactivation in ipsilateral spinal cord dorsal horn, indicating central sensitization might occur. Finally, LAS model mice respond to ibuprofen, a drug clinically used to treat ankle sprain pain. Conclusion: Our study found LAS model mice may be used as a preclinical animal model for screening novel targets or therapies for ankle sprain. Thus, the study may further help to understand molecular mechanisms contributing to ankle sprain-induced pain.
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BACKGROUND: Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients' life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics. METHODS: The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice. RESULTS: CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5-/-) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5-/- mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice. CONCLUSIONS: These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.
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Quimiocina CXCL13 , Dolor Crónico , Receptores CXCR5 , Distrofia Simpática Refleja , Animales , Ratones , Quimiocina CXCL13/metabolismo , Modelos Animales de Enfermedad , Hiperalgesia , Enfermedades Neuroinflamatorias , FN-kappa B , Asta Dorsal de la Médula Espinal , Receptores CXCR5/metabolismoRESUMEN
Nociplastic pain is a severe health problem, while its mechanisms are still unclear. (R, S)-3,5-Dihydroxyphenylglycine (DHPG) is a group I metabotropic glutamate receptor (mGluR) agonist that can cause central sensitization, which plays a role in nociplastic pain. In this study, after intrathecal injection of 25 nmol DHPG for three consecutive days, whole proteins were extracted from the L4~6 lumbar spinal cord of mice 2 h after intrathecal administration on the third day for proteomics analysis. Based on the results, 15 down-regulated and 20 up-regulated proteins were identified in mice. Real-time quantitative PCR (RT-qPCR) and western blotting (WB) revealed that the expression of ectopic P granules protein 5 homolog (EPG5) mRNA and protein were significantly up-regulated compared with the control group, which was consistent with the proteomics results. Originally identified in the genetic screening of Caenorhabditis elegans, EPG5 is mainly involved in regulating autophagy in the body, and in our study, it was mainly expressed in spinal neurons, as revealed by immunohistochemistry staining. After the intrathecal injection of 8 µL adeno-associated virus (AAV)-EPG5 short hairpin RNA (shRNA) to knock down spinal EPG5, the hyperalgesia caused by DHPG was relieved. Altogether, these results suggest that EPG5 plays an important role in DHPG-induced pain sensitization in mice.
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Gránulos de Ribonucleoproteína de Células Germinales , Receptores de Glutamato Metabotrópico , Ratones , Animales , Receptores de Glutamato Metabotrópico/metabolismo , Dolor/metabolismo , Hiperalgesia , Proteínas Relacionadas con la Autofagia , Proteínas de Transporte VesicularRESUMEN
OBJECTIVE: The dorsal approach is commonly used in open wrist arthrodesis. However, the extensor compartments and the dorsal wrist capsule need to be opened. We propose and evaluate a lateral approach using a small incision over the scaphoid anatomical snuffbox, which could be more straightforward for performing scaphoid excision and capitolunate arthrodesis in the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC). METHODS: Between 2016 and 2021, 10 patients were enrolled retrospectively and underwent the lateral approach for scaphoid excision and capitolunate arthrodesis. We presented the radiographic outcomes, including fusion status, capitolunate angle, and carpal height ratio. The functional outcomes of wrist range of motion, grip strength, visual analog scale (VAS) score for pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and Mayo wrist score were evaluated. The data obtained were analyzed and presented as the mean and standard deviation (SD). RESULTS: All 10 patients achieved solid bone fusion, and the mean follow-up period was 20.4 (range 12-38; SD 10.1) months. Postoperatively, the mean capitolunate angle and carpal height ratio improved from 18.1° (range 8-34°; SD 8.6°) to 2.9° (range 0-5°; SD 1.9°) and 0.45 (range 0.40-0.49; SD 0.03)% to 0.50 (range 0.46-0.54; SD 0.02)%, respectively. The average preoperative and final follow-up functional results were as follows: flexion-extension arc of 76.5° (range 50-110°; SD 20.0°) and 74.0° (range 65-90°; SD 9.1°); VAS pain score of 5.8 (range 4-7; SD 1.0) and 0.9 (range 0-2; SD 0.6); QuickDASH score of 55.9 (range 40.9-79.5; SD 11.4) and 26.1 (range 18.2-36.4; SD 6.0); and Mayo wrist score of 46.5 (range 25-60; SD 13.8) and 72.5 (range 70-80; SD 3.5), respectively. CONCLUSIONS: The lateral approach for scaphoid excision and capitolunate arthrodesis in treating SLAC and SNAC can provide a straightforward way for performance. This approach does not require disruption of the dorsal wrist capsule and extensor retinaculum. Bony healing can be achieved, and functional outcomes can be improved.
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Inestabilidad de la Articulación , Hueso Escafoides , Humanos , Muñeca , Estudios Retrospectivos , Hueso Escafoides/diagnóstico por imagen , Hueso Escafoides/cirugía , Artrodesis/métodos , Inestabilidad de la Articulación/cirugía , Dolor , Rango del Movimiento ArticularRESUMEN
For Bennett fractures with tiny avulsion fragments, healing may be jeopardized owing to limited fracture contact surface if displacement of reduced fracture junctions occurs. This study aimed to assess the efficacy of treating Bennett fractures with tiny avulsion fragments using percutaneous small-diameter K-wires for tiny fragment fixation and thumb carpometacarpal (CMC) joint transfixation. From 2011 to 2019, we retrospectively enrolled patients with Gedda type 3 Bennett fractures who underwent operation with K-wire percutaneous pinning for the tiny fragment and CMC joint. We enrolled a total of 13 patients (13 fractures) with a mean age of 26.9 years (range, 18-42 years) at operation and a mean follow-up time of 17.9 months (range, 12-34 months). At the final follow-up, the shortened Disabilities of the Arm, Shoulder and Hand Questionnaire mean score was 4.7, and the visual analog scale score for pain during activity was 0.7. Mean grip strength was 34.7 kg (97.7% of the value on the unaffected side). Mean pinch strength was 5.4 kg (90.5% of the value on the unaffected side). Mean first web opening angle was 66.2° (96.6% of the value on the unaffected side). There were no changes in gap and step-off during the healing process and no osteoarthritic changes in the thumb CMC joint at the final follow-up. For Bennett fractures with tiny avulsion fragment, percutaneous treatment with small-diameter K-wires for fragment fixation and thumb CMC joint transfixation provides a viable alternative with fracture healing and good functional outcomes. [Orthopedics. 2023;46(2):103-107.].
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Fracturas Óseas , Luxaciones Articulares , Traumatismos de la Muñeca , Humanos , Adulto , Fijación Interna de Fracturas , Estudios Retrospectivos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Luxaciones Articulares/cirugíaRESUMEN
INTRODUCTION: Fixed-angle plate fixation can be an effective treatment for distal radius fractures (DRFs). However, patients with existing ulnar positive variance might be at risk of developing symptoms of ulnar-sided wrist pain (USWP). Ulnar shortening osteotomy (USO) is one of the main treatment options for USWP. We hypothesized that a limited radial distraction at the fracture site at the time of surgery for DRF would be functionally equivalent to an indirect USO and that if this were done in a patient with an ulnar plus morphology it could potentially decrease the risk of USWP. METHODS: This retrospective study was conducted at a single institution and all the surgeries were performed by single surgeon. A total of 136 patients (92 women and 44 men) with a mean age of 55 years were enrolled with 57 patients in the distraction group (from 2014 to 2017) and 79 patients (from 2011 to 2013) in the non-distraction group. Patients were assessed USWP. Functional outcomes were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Visual Analogue Scale (VAS) for pain, grip strength, and range of motion for the wrist. RESULTS: The mean follow-up was 37.9 months (range, 28-61 months). The radiographs at postoperative 2-year follow-ups showed the mean ulnar positive variance was 1.3 mm (range, 1-2 mm) in the distraction group and 3.5 mm (range, 2-5 mm) in the non-distraction group. The average of the distraction length was 2.32 mm (range, 2-3 mm). At the 2-year follow-ups, USWP presented in 7% (four patients) in the distraction group, which was significantly less than the incidence of 28% (22 patients) in the non-distraction group. The distraction group exhibited significantly better DASH scores and grip strength and less subsequent ulnar-shortening osteotomy for ulnar-sided wrist pain. CONCLUSIONS: The radial distraction procedure performed during DRFs fixation could possibly reduce the occurrence of postoperative USWP and improve the functional outcomes. LEVEL OF EVIDENCE: Level III, Therapeutic.
Asunto(s)
Fracturas del Radio , Femenino , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dolor/etiología , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/etiología , Fracturas del Radio/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento , Cúbito/diagnóstico por imagen , Cúbito/cirugía , MuñecaRESUMEN
Complex regional pain syndrome type-I (CRPS-I) is a chronic neurological disorder that results in severe pain and affects patients' life quality. Conventional therapies usually lack effectiveness. Electroacupuncture (EA) is an effective physical therapy for relieving CRPS-I pain. However, the mechanism underlying EA-induced analgesia on CRPS-I still remain unknown. Spinal NLRP3 inflammasome was recently identified to contribute to pain and neuroinflammation in a rat model of CRPS-I by our group. Here, we aimed to study whether EA could inhibit spinal NLRP3 inflammasome activation, thus resulting in pain relief and attenuation of spinal neuroinflammation in the rat model of CRPS-I. We established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I. CPIP rats developed remarkable mechanical allodynia that could be relieved by daily EA intervention. NLRP3 inflammasome was activated in spinal cord dorsal horn (SCDH) of CPIP rats, accompanied with over-production of pro-inflammatory cytokine IL-1ß. Immunostaining revealed that the cellular distribution of NLRP3 was predominantly located in SCDH neurons. Pharmacological activation of NLRP3 inflammasome per se is sufficient to produce persistent mechanical allodynia in naïve animals, whereas blocking NLRP3 inflammasome attenuates mechanical allodynia of CPIP rats. EA exclusively reduced NLRP3 overexpression in SCDH neurons and attenuated spinal glial cell over-activation in CPIP rats. EA-induced anti-allodynia with attenuation of spinal glial cell over-activation were all mimicked by intrathecal blocking NLRP3 inflammasome and reversed by activating NLRP3 inflammasome, respectively, through pharmacological methods. Finally, spinal blocking IL-1ß attenuated mechanical allodynia and spinal glial cell over-activation in CPIP rats, resembling the effects of EA. In all, these results demonstrate that spinal NLRP3 inflammasome activation contributes to mechanical allodynia of the rat model of CRPS-I and EA ameliorates mechanical allodynia through inhibiting NLRP3 inflammasome activation in SCDH neurons. Our study further supports EA can be used as an effective treatment for CRPS-I.
RESUMEN
Complex regional pain syndrome type-I (CRPS-I) represents a type of neurovascular condition featured by severe pain in affected extremities. Few treatments have proven effective for CRPS-I. Electroacupuncture (EA) is an effective therapy for pain relief. We explored the mechanism through which EA ameliorates pain in a rat CRPS-I model. The chronic postischemic pain (CPIP) model was established using Sprague-Dawley rats to mimic CRPS-I. We found that oxidative stress-related biological process was among the predominant biological processes in affected hindpaw of CPIP rats. Oxidative stress occurred primarily in local hindpaw but not in the spinal cord or serum of model rats. Antioxidant N-acetyl cysteine (NAC) attenuated mechanical allodynia and spinal glia overactivation in CPIP model rats, whereas locally increasing oxidative stress is sufficient to induce chronic pain and spinal glia overactivation in naive rats. EA exerted remarkable antiallodynia on CPIP rats by reducing local oxidative stress via enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Pharmacological blocking Nrf2 abolished antioxidative and antiallodynic effects of EA. EA reduced spinal glia overactivation, attenuated the upregulation of inflammatory cytokines, reduced the enhanced TRPA1 channel activity in dorsal root ganglion neurons innervating the hindpaws, and improved blood flow dysfunction in hindpaws of CPIP rats, all of which were mimicked by NAC treatment. Thus, we identified local oxidative injury as an important contributor to pathogenesis of animal CRPS-I model. EA targets local oxidative injury by enhancing endogenous Nrf2-mediated antioxidative mechanism to relieve pain and inflammation. Our study indicates EA can be an alternative option for CRPS-I management.