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1.
Anesthesiology ; 133(3): 611-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32788559

RESUMO

BACKGROUND: Voltage-gated sodium channel Nav1.7 has been validated as a perspective target for selective inhibitors with analgesic and anti-itch activity. The objective of this study was to discover new candidate compounds with Nav1.7 inhibitor properties. The authors hypothesized that their approach would yield at least one new compound that inhibits sodium currents in vitro and exerts analgesic and anti-itch effects in mice. METHODS: In silico structure-based similarity search of 1.5 million compounds followed by docking to the Nav1.7 voltage sensor of Domain 4 and molecular dynamics simulation was performed. Patch clamp experiments in Nav1.7-expressing human embryonic kidney 293 cells and in mouse and human dorsal root ganglion neurons were conducted to test sodium current inhibition. Formalin-induced inflammatory pain model, paclitaxel-induced neuropathic pain model, histamine-induced itch model, and mouse lymphoma model of chronic itch were used to confirm in vivo activity of the selected compound. RESULTS: After in silico screening, nine compounds were selected for experimental assessment in vitro. Of those, four compounds inhibited sodium currents in Nav1.7-expressing human embryonic kidney 293 cells by 29% or greater (P < 0.05). Compound 9 (3-(1-benzyl-1H-indol-3-yl)-3-(3-phenoxyphenyl)-N-(2-(pyrrolidin-1-yl)ethyl)propanamide, referred to as DA-0218) reduced sodium current by 80% with a 50% inhibition concentration of 0.74 µM (95% CI, 0.35 to 1.56 µM), but had no effects on Nav1.5-expressing human embryonic kidney 293 cells. In mouse and human dorsal root ganglion neurons, DA-0218 reduced sodium currents by 17% (95% CI, 6 to 28%) and 22% (95% CI, 9 to 35%), respectively. The inhibition was greatly potentiated in paclitaxel-treated mouse neurons. Intraperitoneal and intrathecal administration of the compound reduced formalin-induced phase II inflammatory pain behavior in mice by 76% (95% CI, 48 to 100%) and 80% (95% CI, 68 to 92%), respectively. Intrathecal administration of DA-0218 produced acute reduction in paclitaxel-induced mechanical allodynia, and inhibited histamine-induced acute itch and lymphoma-induced chronic itch. CONCLUSIONS: This study's computer-aided drug discovery approach yielded a new Nav1.7 inhibitor that shows analgesic and anti-pruritic activity in mouse models.


Assuntos
Analgésicos/uso terapêutico , Desenho de Fármacos , Canal de Sódio Disparado por Voltagem NAV1.7/efeitos dos fármacos , Neuralgia/tratamento farmacológico , Prurido/tratamento farmacológico , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Medicine (Baltimore) ; 99(25): e20484, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569170

RESUMO

BACKGROUND: This study will explore the efficacy and safety of intrathecal baclofen bolus (IBB) on neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS: All potential literatures of IBB on NPP in patients with SCI will be searched from the following electronic databases from inauguration to the January 31, 2020: PUBMED, EMBASE, Cochrane Library, Web of Science, Chinese Scientific Journal Database Information, WANGFANG, and China National Knowledge Infrastructure. In addition, we will search other sources, such as dissertations and reference lists of included trials. There are no restrictions of language and publication status in searching all literature sources. The quality of each eligible trial will be assessed using Cochrane risk of bias tool, and publication bias will be checked using a funnel plot and Egger test. Statistical analysis will be conducted using RevMan 5.3 software. RESULTS: This study will scrutinize the efficacy and safety of IBB on NPP in patients with SCI through pain intensity of NPP, spasticity, walking ability, health-related quality of life, duration of stay at hospital (days), incidence of adverse event, and mortality rate. CONCLUSIONS: The findings of this study will present helpful evidence to judge whether IBB is effective on NPP in patients with SCI or not. STUDY REGISTRATION NUMBER: INPLASY202040192.


Assuntos
Baclofeno/administração & dosagem , Relaxantes Musculares Centrais/administração & dosagem , Neuralgia/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Humanos , Injeções Espinhais , Metanálise como Assunto , Neuralgia/etiologia , Revisões Sistemáticas como Assunto
6.
Medicine (Baltimore) ; 99(25): e20702, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569202

RESUMO

BACKGROUND: This protocol aims to assess the efficacy and safety of Botulinum Toxin Type A (BTTA) for the treatment of neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS: We will retrieve databases in Cochrane Library, EMBASE, MEDLINE, Excerpta Medica Database, PsychINFO, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the beginning to the March 1, 2020. We will consider any potential studies on assessing the efficacy and safety of BTTA for the treatment of NPP in patients with SCI without limitations of language and publication status. Cochrane risk of bias will be used to assess the risk of bias for all included trials. RevMan 5.3 software will be utilized to synthesize the extracted data and to analyze those data. RESULTS: This study will appraise the efficacy and safety based on the current evidence of BTTA for the treatment of NPP in patients with SCI. CONCLUSION: This study will exert high quality clinical trials for exploring the efficacy and safety of BTTA in treating NPP in patients with SCI. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020170474.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Fármacos Neuromusculares/uso terapêutico , Traumatismos da Medula Espinal/complicações , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
7.
Plast Reconstr Surg ; 146(1): 157-170, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32590660

RESUMO

BACKGROUND: Since their introduction to clinical medicine in 1989, botulinum toxin injections have been used for many indications. First used for nonsurgical management of strabismus, botulinum toxin injections are now widely used in plastic and reconstructive surgery for aesthetic indications; however, nonaesthetic indications of botulinum toxin have grown tremendously over the past two decades and span numerous specialties, including urology, dermatology, ophthalmology, otolaryngology, gynecology, plastic surgery, general surgery, and neurology. The present review aims to highlight nonaesthetic indications of botulinum toxin that are most relevant to the plastic surgeon with an emphasis on evidence-based practice. METHODS: A PubMed search with manual reference checking was conducted to find the most relevant and influential articles on the nonaesthetic uses of botulinum toxin within the realm of adult plastic surgery. Studies were then categorized into areas of use, and quality of evidence for each category was highlighted. RESULTS: Botulinum toxin has numerous nonaesthetic indications in plastic surgery, including for select pain-related disorders, skeletal muscle activity disorders, exocrine gland hyperfunction, wound healing, Raynaud phenomenon, abdominal wall reconstruction, and prosthetic breast reconstruction and augmentation. Although these indications have been widely reported, high-quality evidence supporting efficacy, optimal dose, and injection protocol with randomized controlled trials is lacking in many areas. CONCLUSIONS: Botulinum toxin is widely used in plastic surgery for a variety of nonaesthetic indications. Future studies should focus on investigating efficacy and best practice with high level of evidence research.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Fármacos Neuromusculares/uso terapêutico , Cirurgia Plástica , Humanos , Neuralgia/tratamento farmacológico , Manejo da Dor/métodos , Complicações Pós-Operatórias/tratamento farmacológico , Cirurgia Plástica/métodos
8.
Expert Opin Pharmacother ; 21(11): 1377-1387, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32511032

RESUMO

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Neuralgia/tratamento farmacológico , Administração Tópica , Analgésicos/efeitos adversos , Capsaicina/efeitos adversos , Análise Custo-Benefício , Prova Pericial , Humanos , Neuralgia/metabolismo , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Qualidade de Vida , Canais de Cátion TRPV/metabolismo , Adesivo Transdérmico
9.
Neurología (Barc., Ed. impr.) ; 35(5): 291-294, jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188625

RESUMO

INTRODUCCIÓN: La infección por SARS-CoV-2y la situación de pandemia hacen necesario un cambio en nuestra práctica clínica, en relación con la adopción de nuevas estrategias que permitan la asistencia integral de los pacientes con cefalea y neuralgia. MATERIAL Y MÉTODOS: Ante la elevada capacidad de transmisión del virus, determinados procedimientos, como la infiltración de OnabotulinumtoxinA y la realización de bloqueos anestésicos, deben realizarse adoptando medidas que garanticen un nivel adecuado de seguridad. RESULTADOS: Nuestro objetivo es presentar una serie de recomendaciones basadas en las medidas establecidas por nuestro sistema sanitario para evitar el contagio. Diferenciaremos entre aquellas medidas relacionadas con el paciente y el facultativo, con la técnica, con la infraestructura (sala de espera y consulta) y con la gestión asistencial


INTRODUCTION: The COVID-19 pandemic has given rise to the need for changes in clinical practice, with new strategies to enable integrated care for patients with headache and neuralgia. METHODS: Given the high spreadability of SARS-CoV-2, new safety measures are required in such procedures as onabotulinumtoxinA infiltration and nerve blocks. RESULTS: We present a series of recommendations based on the measures implemented to prevent infection in our healthcare system. We differentiate between measures related to patients and physicians, to technique, to infrastructure (waiting room and consultation), and to healthcare managemen


Assuntos
Humanos , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/normas , Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/administração & dosagem , Bloqueio Nervoso/métodos , Bloqueio Nervoso/normas , Segurança do Paciente/normas , Infecções por Coronavirus/prevenção & controle , Pneumonia Viral/prevenção & controle , Pandemias , Cefaleia/tratamento farmacológico , Neuralgia/tratamento farmacológico
11.
Neurologia ; 35(5): 291-294, 2020 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32410765

RESUMO

INTRODUCTION: The COVID-19 pandemic has given rise to the need for changes in clinical practice, with new strategies to enable integrated care for patients with headache and neuralgia. MATERIAL AND METHODS: Given the high spreadability of SARS-CoV-2, new safety measures are required in such procedures as onabotulinumtoxinA infiltration and nerve blocks. RESULTS: We present a series of recommendations based on the measures implemented to prevent infection in our healthcare system. We differentiate between measures related to patients and physicians, to technique, to infrastructure (waiting room and consultation), and to healthcare management.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Cefaleia/tratamento farmacológico , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Bloqueio Nervoso/métodos , Neuralgia/tratamento farmacológico , Saúde do Trabalhador , Segurança do Paciente , Pneumonia Viral/virologia
12.
Anesthesiology ; 133(1): 154-164, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32384291

RESUMO

BACKGROUND: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks. METHODS: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo.The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. RESULTS: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was -0.2 (95% CI [-0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [-0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [-0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event. CONCLUSIONS: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive-emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.


Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Neuralgia/tratamento farmacológico , Adulto , Idoso , Cognição/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Emoções , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neuralgia/psicologia , Medição da Dor/efeitos dos fármacos , Resultado do Tratamento
13.
J Headache Pain ; 21(1): 54, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429883

RESUMO

BACKGROUND: Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored. METHODS: This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis. RESULTS: Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7 ± 15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥ 300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14-118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09-1.18), older age (OR 1.01 per year, 95% CI 1.01-1.01), indications other than PHN, especially epilepsy (OR 8.04, 95% CI 7.33-8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI = 1.10-1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35-0.47). CONCLUSIONS: Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was frequently below the recommended ranges. Potential causes included the duration of natural history of PHN, and off-label prescriptions for pain in acute herpes zoster, rather than PHN, as well as intolerance to the side effects.


Assuntos
Analgésicos/administração & dosagem , Medição da Dor/efeitos dos fármacos , Vigilância da População , Pregabalina/administração & dosagem , Adulto , Idoso , Estudos de Coortes , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Fibromialgia/tratamento farmacológico , Fibromialgia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia Pós-Herpética/epidemiologia , Medição da Dor/métodos , Vigilância da População/métodos , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do Tratamento
16.
Braz J Med Biol Res ; 53(5): e9255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348427

RESUMO

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.


Assuntos
Indometacina/administração & dosagem , Neuralgia/tratamento farmacológico , Medição da Dor , Nervo Isquiático/lesões , Animais , Constrição , Modelos Animais de Doenças , Masculino , Neuralgia/etiologia , Limiar da Dor , Ratos , Ratos Sprague-Dawley , Ratos Wistar
17.
Expert Opin Pharmacother ; 21(8): 983-991, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32252557

RESUMO

BACKGROUND: Chronic pain is often difficult to treat, and many patients are not satisfied with analgesic treatment. The authors assessed patient satisfaction with oral analgesics in patients with chronic pain in Japan. RESEARCH DESIGN AND METHODS: This was an observational cross-sectional study conducted in dispensing pharmacies. A patient satisfaction questionnaire survey was conducted in 781 patients prescribed one nonsteroidal anti-inflammatory drug (NSAID) or neuropathic pain (NeP) drug for at least 90 consecutive days. The primary endpoint was patient satisfaction with analgesics. The secondary endpoints were pain relief, activity of daily living (ADL) improvement and doctor-patient communication. RESULTS: The proportions of patients who answered 'satisfied if anything' or better for patient satisfaction in the NSAID and NeP drug groups were 70.0% and 65.2%, respectively, whereas those of patients who answered 'satisfied' were 43.3% and 29.4%, respectively. The proportions of patients with improved pain relief, ADL improvement, and good doctor-patient communication were numerically higher than those of patients who answered 'satisfied if anything' or better. CONCLUSIONS: Approximately two-thirds of the patients were satisfied with current analgesics. Patient satisfaction with oral analgesics could be influenced by multiple factors. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000036456.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/tratamento farmacológico , Neuralgia/tratamento farmacológico , Manejo da Dor/métodos , Satisfação do Paciente , Atividades Cotidianas , Administração Oral , Adulto , Idoso , Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Medição da Dor , Inquéritos e Questionários
18.
Pain Res Manag ; 2020: 9353940, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318131

RESUMO

Background: Neuropathic pain has a prevalence of 2-17% in the general population. Diagnosis and treatment of neuropathic pain are not fully described in different populations. The aim was to determine the treatment patterns and direct costs of care associated with the management of neuropathic pain from the onset of the first symptom to up to two years after diagnosis. Methods: From a drug-claim database, a cohort of randomly selected outpatients diagnosed with neuropathic pain was obtained from an insurer in Colombia and followed up for two years after diagnosis. The clinical records were reviewed individually to identify the study variables, including the time needed to make the diagnosis, the medical and paraclinical resources used, the pharmacological therapy for pain management, and the direct costs associated with care. Results: We identified 624 patients in 49 cities, with a mean age of 50.3 ± 14.1 years, of which 324 were men (51.9%). An average of 90 days passed from the initial consultation until the diagnosis of neuropathic pain, the most frequent being lumbosacral radiculopathy (57.9%). 34.5% of the cohort had at least one diagnostic imaging procedure, and 16% had an electromyography. On average, they were treated by a general practitioner twice. 91.7% received initial treatment with tramadol, carbamazepine, amitriptyline, imipramine, or pregabalin, and 60.4% received combined therapy. The mean cost of care for two years for each patient was US$246.3. Conclusions: Patients with neuropathic pain in Colombia are being diagnosed late, are using therapeutic agents not recommended as first-line treatment by clinical practice guidelines, and are being treated for short periods of time.


Assuntos
Analgésicos/economia , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/economia , Manejo da Dor/economia , Adulto , Estudos de Coortes , Colômbia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Manejo da Dor/métodos , Padrões de Prática Médica/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos
20.
Am J Chin Med ; 48(2): 407-428, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138533

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of cisplatin, which is characterized by intolerable paresthesia, burning, and hyperalgesia, and severely impacts the life quality of patients. However, no clearly potent drug has been found for clinical medication due to its undefined mechanism. Corydalis Saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulations improvement, hemostasis, and analgesia. This study was designed to observe the effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cisplatin-induced neuropathic pain and to explore its potential mechanisms. In this study, the rats received intraperitoneal injection of 2mg/kg cisplatin twice a week for five weeks. Meanwhile, oral administration of low (30mg/kg)-, medium (60mg/kg)- and high (120mg/kg)-dose CSBTA were given daily for five weeks. By using Von-frey hair, heat radiant and -80∘C cold acetone, we found that CSBTA could obviously relieve cisplatin-induced mechanical, heat, and cold hyperalgesia. It has been verified that cisplatin-induced peripheral neuropathy is related to intraepidermal nerve fibers loss and activation of inflammation downstream. Our research found that Tumor necrosis factor-alpha (TNF-α), Interleukin-1beta (IL-1ß), and Prostaglandin E2 (PGE2) were significantly increased by 10 intraperitoneal injections of cisplatin, and such pro-inflammation cytokines could be reduced via CSBTA administration. Besides, in the cisplatin model group, the neuronal structures of dorsal root ganglia (DRG) were severely damaged and the loss of intraepidermal nerve fibers occurred; but in the CSBTA administration groups, all above pathological changes were improved. Moreover, CSBTA could normalize the overexpression levels of p-p38 and Transient receptor potential vanilloid receptor (TRPV1) induced by cisplatin in DRG, trigeminal ganglion (TG), spinal cord, and foot of rats. In summary, we considered that CSBTA exerted its therapeutic effects by ameliorating neuronal damages, improving intraepidermal nerve fiber (IENF) loss, and inhibiting inflammation-induced p38 phosphorylation to block TRPV1 activation. These findings were the first to confirm the analgesic effect of CSBTA on CIPN and suggested a novel strategy for treating CIPN in clinic.


Assuntos
Alcaloides/farmacologia , Alcaloides/uso terapêutico , Analgésicos , Cisplatino/efeitos adversos , Corydalis/química , Neuralgia/induzido quimicamente , Neuralgia/genética , Fitoterapia , Canais de Cátion TRPV/metabolismo , Alcaloides/isolamento & purificação , Animais , Neuralgia/tratamento farmacológico , Ratos
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