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1.
Cells ; 12(23)2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38067126

RESUMO

Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-ß, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 µL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.


Assuntos
Células Endoteliais , Exossomos , Humanos , Ratos , Animais , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Âmnio/metabolismo , Angiogênese , Peróxido de Hidrogênio/farmacologia , Cicatrização/fisiologia , Células-Tronco , Colágeno/farmacologia , Fator de Crescimento Epidérmico/farmacologia
2.
Nutrients ; 15(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37242259

RESUMO

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury and pain, as well as acute and chronic diseases. Since long-term uses of synthetic steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) was found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In a subcutaneous air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells, and inflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß concentrations, as achieved with dexamethasone (a representative steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (a representative NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS-NO and COX-2-PG pathways, and that PVRE could be a potential candidate as an anti-inflammatory material for diverse tissue injuries.


Assuntos
Antioxidantes , Extratos Vegetais , Humanos , Extratos Vegetais/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Antioxidantes/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Anti-Inflamatórios não Esteroides/uso terapêutico , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Dexametasona/efeitos adversos , Óxido Nítrico/metabolismo , Lipopolissacarídeos/farmacologia
3.
Int J Mol Sci ; 24(9)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37175778

RESUMO

Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 108 exosomes in 10 µL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 µg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.


Assuntos
Exossomos , Glaucoma , Ratos , Humanos , Animais , Pressão Intraocular , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Exossomos/metabolismo , Âmnio/metabolismo , Peróxido de Hidrogênio/metabolismo , Glaucoma/metabolismo , Retina/metabolismo , Fatores de Crescimento Neural/metabolismo , Células-Tronco/metabolismo , Modelos Animais de Doenças
4.
J Pain ; 23(12): 2092-2109, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35940543

RESUMO

MAO-B inhibitors have been implicated to reverse neuropathic pain behaviors. Our previous study has demonstrated that KDS2010 (KDS), a newly developed reversible MAO-B inhibitor, could attenuate Paclitaxel (PTX)-induced tactile hypersensitivity in mice through suppressing reactive oxidant species (ROS)-decreased inhibitory GABA synaptic transmission in the spinal cord. In this study, we evaluated the analgesic effect of KDS under a new approach, in which KDS acts on dorsal horn sensory neurons to reduce excitatory transmission. Oral administration of KDS effectively enhanced mechanical thresholds in the spinal nerve ligation (SNL) induced neuropathic pain in rats. Moreover, we discovered that although treatment with KDS increased brain-derived neurotrophic factor (BDNF) levels, KDS inhibited Tropomyosin receptor kinase B (TrkB) receptor activation, suppressing increased p-NR2B-induced hyperexcitability in spinal dorsal horn sensory neurons after nerve injury. In addition, KDS showed its anti-inflammatory effects by reducing microgliosis and astrogliosis and the activation of MAPK and NF-ᴋB inflammatory pathways in these glial cells. The levels of ROS production in the spinal cords after the SNL procedure were also decreased with KDS treatment. Taken together, our results suggest that KDS may represent a promising therapeutic option for treating neuropathic pain. PERSPECTIVE: Our study provides evidence suggesting the mechanisms by which KDS, a novel MAO-B inhibitor, can be effective in pain relief. KDS, by targeting multiple mechanisms involved in BDNF/TrkB/NR2B-related excitatory transmission and neuroinflammation, may represent the next future of pain medicine.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neuralgia , Ratos , Camundongos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Espécies Reativas de Oxigênio/uso terapêutico , Ratos Sprague-Dawley , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nervos Espinhais , Medula Espinal , Monoaminoxidase/metabolismo , Monoaminoxidase/farmacologia , Monoaminoxidase/uso terapêutico
5.
Mol Brain ; 15(1): 41, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526002

RESUMO

Monoamine oxidase (MAO) inhibitors have been investigated for the treatment of neuropathic pain. Here, we assessed the antiallodynic effects of a novel MAO-B inhibitor, KDS2010, on paclitaxel (PTX)-induced mechanical hypersensitivity. Oral administration of KDS2010 effectively relieved PTX-induced mechanical hypersensitivity in a dose-dependent manner. KDS2010 (25 mg/Kg) significantly prevented and suppressed PTX-induced pain responses with minimal effects on the body weight, motor activity, and working memory. KDS2010 significantly reduced reactive astrocytosis and reactive oxygen species (ROS) level in the L4-L6 spinal cord of PTX-treated mice. Furthermore, KDS2010 reversed the attenuation of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency in spinal dorsal horn neurons, although it failed to restore the reduced tonic GABAA inhibition nor the increased GABA transporter 1 (GAT1) expression in PTX-treated mice. In addition, bath application of a reactive oxygen species (ROS) scavenger (PBN) restored the sIPSC frequency in PTX-treated mice but not in control and PTX + KDS2010-treated mice. These results indicated that the antiallodynic effect of KDS2010 is not due to a MAO-B-dependent GABA production. Finally, PBN alone also exerted a similar analgesic effect as KDS2010, but a co-treatment of PBN with KDS2010 showed no additive effect, suggesting that inhibition of MAO-B-dependent ROS production is responsible for the analgesic effect by KDS2010 on PTX-induced allodynia. Overall, KDS2010 attenuated PTX-induced pain behaviors by restoring the altered ROS level and GABAergic inhibitory signaling in the spinal cord, suggesting that KDS2010 is a promising therapeutic strategy for chemotherapy-induced peripheral neuropathy.


Assuntos
Analgésicos , Inibidores da Monoaminoxidase , Neuralgia , Analgésicos/farmacologia , Animais , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Camundongos , Inibidores da Monoaminoxidase/farmacologia , Neuralgia/tratamento farmacológico , Paclitaxel/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Medula Espinal/metabolismo , Ácido gama-Aminobutírico/farmacologia
6.
J Clin Med ; 11(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35407380

RESUMO

(1) Background: Prolonged neck flexion is thought to cause harmful loading on the cervical spine. Along with the degenerative process, cervical alignment tends to change toward lordotic curvature. The association between cervical alignment and cervical spondylosis remains unclear. (2) Methods: Three raters retrospectively assessed cervical radiographies of outpatients at a tertiary center in 2019 using degenerative cervical spondylosis score (DCS score; a newly developed scoring system), C2-7 absolute rotational angle (ARA), and C2-7 sagittal vertical axis (SVA). (3) Results: A total of 561 patients were included in the analysis. Multiple regression analysis with adjustments for age and sex revealed that C2-7 ARA, rather than SVA, was a significant parameter for degenerative spondylosis. The interaction between age and C2-7 ARA was significant, indicating that the increase in DCS score with increasing age was more pronounced in patients with kyphotic cervical alignment. The direct effect of age on DCS score was 0.349 (95% CI 0.319 to 0.380, p < 0.001) and the proportion of the mediation effect of C2-7 ARA was −0.125 (p < 0.001). (4) Conclusions: C2-7 ARA was significantly associated with DCS after adjustment for both age and sex. Subjects with more kyphotic cervical alignment showed a greater correlation between increased DCS score and older age.

7.
Korean J Anesthesiol ; 75(3): 231-244, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34638182

RESUMO

BACKGROUND: Various regional analgesia techniques are used to reduce postoperative pain in patients undergoing video-assisted thoracic surgery (VATS). This study aimed to determine the relative efficacy of regional analgesic interventions for VATS using a network meta-analysis (NMA). METHODS: We searched the Medline, EMBASE, Cochrane Controlled Trial Register, Web of Science, and Google Scholar databases to identify all randomized controlled trials (RCTs) that compared the analgesic effects of the following interventions: control, thoracic paravertebral block (TPVB), erector spinae plane block (ESPB), serratus plane block (SPB), and intercostal nerve block (INB). The primary outcome was opioid consumption during the first 24-h postoperative period. Pain scores were also collected during three different postoperative periods: the early (0-6 h), middle (6-18 h), and late (18-24 h) periods. RESULTS: A total of 21 RCTs (1391 patients) were included. TPVB showed the greatest effect on opioid consumption compared with the control (mean difference [MD] = -13.2 mg; 95% CI [-16.2, -10.1]). In terms of pain scores in the early period, ESPB had the greatest effect compared to control (MD = -1.6; 95% CI [-2.3, -0.9]). In the middle and late periods, pain scores showed that TPVB, ESPB and INB had superior analgesic effects compared to controls, while SPB did not. CONCLUSIONS: TPVB had the best analgesic efficacy following VATS, though the analgesic efficacy of ESPBs was comparable. However, further studies are needed to determine the optimal regional analgesia technique to improve postoperative pain control following VATS.


Assuntos
Analgesia , Cirurgia Torácica Vídeoassistida , Analgésicos Opioides , Humanos , Metanálise em Rede , Dor Pós-Operatória/prevenção & controle
8.
Ann Palliat Med ; 11(4): 1222-1230, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34894702

RESUMO

BACKGROUND: Motor-sparing regional anesthesia modalities, such as periarticular infiltration (PAI) and pericapsular nerve group (PENG) block, have become the mainstay of multimodal approaches used during total hip arthroplasty (THA). We hypothesized that the postoperative analgesia of the PENG block was non-inferior to that of the PAI. METHODS: Sixty patients were randomly allocated into two groups. The PAI group were injected with 100 mL of cocktail solution (ropivacaine 20 mL, ketorolac 2 mL, and epinephrine 1 mL mixed with normal saline) in periarticular tissues directly by the surgeon. The PENG group were injected with 30 mL of 0.5% ropivacaine in the iliopubic eminence plane by ultrasound. The primary outcome was the resting pain score 12 h after surgery, and the prespecified non-inferiority was 1. Additionally, the cumulative opioid consumption and quality of recovery were evaluated. RESULTS: The mean difference in pain score 12 h postoperatively between the PENG and PAI groups was 0.6 [95% confidence interval (CI): -0.8 to 2.0]. The upper 95% CI exceeded the non-inferiority margin of 1 at all postoperative time points. There was no difference in opioid consumptions and quality of recovery scores. CONCLUSIONS: PENG block provided comparable analgesia with PAI following THA. It is not conclusive that PENG is inferior or non-inferior to PAI based on our study. TRIAL REGISTRATION: Clinical Research information Service (CRIS, https://cris.nih.go.kr, KCT0006049).


Assuntos
Artroplastia de Quadril , Analgésicos , Analgésicos Opioides/uso terapêutico , Nervo Femoral , Humanos , Dor Pós-Operatória/prevenção & controle , Ropivacaina/uso terapêutico
9.
BMC Anesthesiol ; 21(1): 310, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893034

RESUMO

BACKGROUND: The clinical range of central venous pressure (CVP) (typically 5 to 15 mmHg) is much less than the range of mean arterial blood pressure (60 to 120 mmHg), suggesting that CVP may have little impact on estimation of systemic vascular resistance (SVR). The accuracy and feasibility of using an arbitrary CVP rather than actual CVP for the estimation of SVR during intraoperative period is not known. METHODS: Using vital records obtained from patients who underwent neurological and cardiac surgery, the present study retrospectively calculated SVR using fixed values of CVP (0, 5, 10, 15, and 20 mmHg) and randomly changing values of CVP (5 to 15 mmHg) and compared these calculated SVRs with actual SVR, calculated using actual CVP. Differences between actual SVR and SVRs based on fixed and random CVPs were quantified as root mean square error (RMSE) and mean absolute percentage error (MAPE). Bland-Altman analysis and four-quadrant plot analysis were performed. RESULTS: A total of 34 patients are included, including 18 who underwent neurosurgery and 16 who underwent cardiac surgery; 501,380 s (139.3 h) of data was analyzed. The SVR derived from a fixed CVP of 10 mmHg (SVRf10) showed the highest accuracy (RMSE: 115 and 104 [dynes/sec/cm- 5] and MAPE: 6.3 and 5.7% in neurological and cardiac surgery, respectively). The 95% limits of agreement between SVRf10 and actual SVR were - 208.5 (95% confidence interval [CI], - 306.3 to - 148.1) and 242.2 (95% CI, 181.8 to 340.0) dynes/sec/cm- 5 in neurosurgery and - 268.1 (95% CI, - 367.5 to - 207.7) and 163.2 (95% CI, 102.9 to 262.6) dynes/sec/cm- 5 in cardiac surgery. All the SVRs derived from the fixed CVPs (regardless of its absolute value) showed excellent trending ability (concordance rate > 0.99). CONCLUSIONS: SVR can be estimated from a fixed value of CVP without causing significant deviation or a loss of trending ability. However, caution is needed when using point estimates of SVR when the actual CVP is expected to be out of the typical clinical range. TRIAL REGISTRATION: This study was registered Clinical Research Information Service, a clinical trial registry in South Korea ( KCT0006187 ).


Assuntos
Pressão Venosa Central/fisiologia , Resistência Vascular/fisiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34948643

RESUMO

(1) Background: Although radiography performed on the subject in an upright position is considered the standard method for assessing sagittal cervical alignment, it is frequently determined, or reported, based on MRI performed on the subject in a supine position. (2) Methods: Cervical alignment observed in both imaging modalities was assessed using four methods: the C2-7 Cobb angle, the absolute rotation angle (ARA), Borden's method, and the sagittal vertical axis (SVA). Cervical alignment was determined (lordosis, kyphosis, and straight) based on radiography. Then, the diagnostic cut-off values for the MRI images and their corresponding diagnostic accuracies were assessed. (3) Results: The analysis included 142 outpatients. The determined diagnostic cut-off values for lordosis, using three measurements (Cobb angle, ARA, and Borden's method), were -8.5°, -12.5°, and 3.5 mm, respectively, and the cut-off values for kyphosis were -4.5°, 0.5°, and -1.5 mm, respectively. The cut-off value for SVA > 40 mm was 19.5 mm. The Cobb angle, ARA, and Borden's method, on MRI, showed high negative predictive values for determining kyphosis. The SVA on MRI measurements also showed high negative predictive values for determining >40 mm. (4) Conclusions: MRI measurements may be predictive of cervical alignment, especially for the exclusion of kyphosis and SVA > 40 mm. However, caution is needed in the other determinations using MRI, as their accuracies are limited.


Assuntos
Cifose , Lordose , Vértebras Cervicais/diagnóstico por imagem , Humanos , Cifose/diagnóstico por imagem , Lordose/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Retrospectivos
11.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073390

RESUMO

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.


Assuntos
Portadores de Fármacos/farmacologia , Quinase I-kappa B/antagonistas & inibidores , Nanopartículas/uso terapêutico , Neuralgia/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , RNA Interferente Pequeno/farmacologia , Animais , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Masculino , Microglia/patologia , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/patologia , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley
12.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806698

RESUMO

Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15-60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.


Assuntos
Formaldeído/farmacologia , Inflamação/metabolismo , Dor/induzido quimicamente , Dor/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Células PC12 , Medição da Dor/métodos , Ratos , Medula Espinal/metabolismo , Regulação para Cima/fisiologia
13.
J Clin Med ; 10(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802457

RESUMO

Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) -0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3-1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.

14.
Int J Mol Sci ; 21(10)2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32423102

RESUMO

Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.


Assuntos
Receptor 1 de Quimiocina CX3C/genética , Nanopartículas/química , Neuralgia/tratamento farmacológico , RNA Interferente Pequeno/farmacologia , Nervos Espinhais/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Receptor 1 de Quimiocina CX3C/antagonistas & inibidores , Humanos , Ligadura , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Neuralgia/genética , Neuralgia/patologia , Manejo da Dor , Medição da Dor/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , RNA Interferente Pequeno/genética , Ratos , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal/patologia , Nervos Espinhais/metabolismo , Nervos Espinhais/patologia
15.
Korean J Pain ; 33(2): 144-152, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235015

RESUMO

BACKGROUND: Hemidiaphragmatic paralysis, a frequent complication of the brachial plexus block performed above the clavicle, is rarely associated with an infraclavicular approach. The costoclavicular brachial plexus block is emerging as a promising infraclavicular approach. However, it may increase the risk of hemidiaphragmatic paralysis because the proximity to the phrenic nerve is greater than in the classical infraclavicular approach. METHODS: This retrospective analysis compared the incidence of hemidiaphragmatic paralysis in patients undergoing costoclavicular and supraclavicular brachial plexus blocks. Of 315 patients who underwent brachial plexus block performed by a single anesthesiologist, 118 underwent costoclavicular, and 197 underwent supraclavicular brachial plexus block. Propensity score matching selected 118 pairs of patients. The primary outcome was the incidence of hemidiaphragmatic paralysis, defined as a postoperative elevation of the hemidiaphragm > 20 mm. Factors affecting the incidence of hemidiaphragmatic paralysis were also evaluated. RESULTS: Hemidiaphragmatic paralysis was observed in three patients (2.5%) who underwent costoclavicular and 47 (39.8%) who underwent supraclavicular brachial plexus blocks (P < 0.001; odds ratio, 0.04; 95% confidence interval, 0.01-0.13). Both the brachial plexus block approach and the injected volume of local anesthetic were significantly associated with hemidiaphragmatic paralysis. CONCLUSIONS: The incidence of hemidiaphragmatic paralysis is significantly lower with costoclavicular than with supraclavicular brachial plexus block.

16.
J Korean Neurosurg Soc ; 58(1): 89-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26279821

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory disease involving multiple joints. The cervical spine is often affected, and cases involving atlantoaxial joint can lead to instability. Anterior atlantoaxial subluxation in RA patients can lead to posterior neck pain or occipital headache because of compression of the C2 ganglion or nerve. Here, we report the successful treatment of a RA patient with occipital radiating headache using pulsed radiofrequency therapy at the C2 dorsal root ganglion.

17.
Korean J Anesthesiol ; 68(2): 136-40, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25844131

RESUMO

BACKGROUND: This study compared intubating conditions and the onset time associated with administration of cisatracurium, a nondepolarizing neuromuscular blocker with a relatively slow onset, according to prior injection of one of two intravenous anesthetic agents: propofol or etomidate. METHODS: Forty-six female patients, undergoing general anesthesia and endotracheal intubation for elective surgery, were randomized to two groups; group P were administered propofol (2 mg/kg) prior to cisatracurium (0.2 mg/kg); group E were administered etomidate (0.3 mg/kg) prior to cisatracurium (0.2 mg/kg). We measured intubating conditions and the onset time according to the types of intravenous anesthetic administered. Measurements of heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken immediately prior to induction; immediately and 1 min after IV anesthetic administration; and immediately and 1, 2, 3, 4, 5, 7, and 15 min after endotracheal intubation. RESULTS: Intubating conditions were superior in group E compared with group P (P = 0.009). The average onset time of cisatracurium was more rapid in group E (155.74 ± 32.92 s vs. 185.26 ± 38.57 s in group P; P = 0.008). There were no group differences in SBP, DBP, and HR following intravenous anesthetic drug injection and endotracheal intubation. However, SBP and DBP were substantially higher in group E after endotracheal intubation. CONCLUSIONS: Etomidate improves intubating conditions and provide a more rapid onset time of cisatracurium during anesthetic induction compared to propofol.

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