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1.
S D Med ; 73(3): 116-121, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32142230

RESUMO

Effective postoperative pain control is an essential component for all patients having a surgical procedure. Given the chronicity of care needed by chronic renal failure patients, providing them excellent pain control during their perioperative transplant period is imperative. Different forms of local anesthetics are available and our purpose was to determine whether liposomal bupivacaine reduces post-operative pain levels better than catheter directed administration of 0.25 percent bupivacaine. Secondary objectives included evaluation of differences in total narcotic use and total length of stay. A retrospective chart review of 57 bupivacaine patients and 40 liposomal bupivacaine patients was completed. The patients' reported pain on a 10-point pain scale, narcotic usage and total length of stay were collected. Results showed lower average pain scores on post-operative day 0 for patients receiving liposomal bupivacaine, as well as a fewer narcotics being used on post-operative day 0 and 1. Patients receiving liposomal bupivacaine also had shorter hospital stays by two days. We conclude that liposomal bupivacaine improved pain control and reduced narcotic use in renal transplant patients.


Assuntos
Anestésicos Locais , Bupivacaína , Transplante de Rim , Analgésicos , Anestésicos Locais/administração & dosagem , Humanos , Lipossomos , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
2.
Zhen Ci Yan Jiu ; 45(1): 40-5, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144907

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Jiaji" (EX-B2) at different time points on the expression of OX-42 (a monoclonal antibody with specific expression of complement receptor-3 in spinal microglial cells) and purinergic receptor P2X4 (P2X4) in rats with chronic constriction injury (CCI) of the sciatic nerve, as well as the possible after-effect mechanism of EA analgesia in neuropathic pain. METHODS: Sprague-Dawley rats were randomly divided into blank group, model group, immediately after EA group, 0.5-hour after EA group, 1-hour after EA group, 2-hour after EA group, 4-hour after EA group, 12-hour after EA group, and 24-hour after EA group, with 6 rats in each group. The rats in the model group and the EA groups were used to establish a model of CCI-induced neuropathic pain, and those in the immediately after EA group and the 0.5, 1, 2, 4, 12 and 24 hours after EA groups were treated with EA at bilateral L3 and L5 "Jiaji" points for 20 min after 7 d of modeling. Samples were collected immediately and at 0.5, 1, 2, 4, 12, and 24 hours after EA, and for the rats in the blank group and the model group, samples were collected after fixation the rats for 20 min. Heat pain threshold was observed before and after intervention, and immunohistochemistry was used to measure the protein expression of OX-42 and P2X4 in the spinal cord lumbar enlargement. RESULTS: After 7 days of modeling (before intervention), compared with the blank group, the heat pain threshold had a significant reduction in the model group and the EA groups (P<0.01). Compared with the model group after intervention, the immediately after EA group and the 0.5, 1 and 2 hours after EA groups had a significant increase in heat pain threshold (P<0.05). Compared with the model group, immediately after EA, the 0.5, 1 and 2 hours after EA groups had a significant reduction in the protein expression of OX-42 (P<0.01), and immediately after EA, the 0.5 and 1 hour after EA groups had a significant reduction in the protein expression of P2X4 (P<0.01). CONCLUSION: EA at "Jiaji" points can significantly increase heat pain threshold and down-regulate the protein expression of OX-42 and P2X4 in the spinal cord of CCI rats. The analgesic effect can last for 2 h.


Assuntos
Eletroacupuntura , Analgésicos , Animais , Constrição , Regulação para Baixo , Ratos , Ratos Sprague-Dawley , Medula Espinal
4.
Chem Pharm Bull (Tokyo) ; 68(2): 140-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009081

RESUMO

Previously, we reported that the c-Met inhibitory effect of Ephedra Herb extract (EHE) is derived from ingredients besides ephedrine alkaloids. Moreover, analgesic and anti-influenza activities of EHE and ephedrine alkaloids-free Ephedra Herb extract (EFE) have been reported recently. In this study, we examined the fractions containing c-Met kinase inhibitory activity from EHE and the fractions with analgesic and anti-influenza activities from EFE, and elucidated the structural characteristics of the active fractions. Significant c-Met kinase activity was observed in 30, 40, and 50% methanol (MeOH) eluate fractions obtained from water extract of EHE using Diaion HP-20 column chromatography. Similarly, 20 and 40% MeOH, and MeOH eluate fractions obtained from water extract of EFE were found to display analgesic and anti-influenza activities. Reversed phase-HPLC analysis of the active fractions commonly showed broad peaks characteristic of high-molecular mass condensed tannin. The active fractions were analyzed using 13C-NMR and decomposition reactions; the deduced structures of active components were high-molecular mass condensed tannins, which were mainly procyanidin B-type and partly procyanidin A-type, including pyrogallol- and catechol-type flavan 3-ols as extension and terminal units. HPLC and gel permeation chromatography (GPC) analyses estimated that the ratio of pyrogallol- and catechol-type was approximately 9 : 2, and the weight-average molecular weight based on the polystyrene standard was >45000. Furthermore, GPC-based analysis was proposed as the quality evaluation method for high-molecular mass condensed tannin in EHE and EFE.


Assuntos
Ephedra/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Cães , Efedrina/química , Efedrina/farmacologia , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Proantocianidinas/química , Proantocianidinas/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
5.
Medicine (Baltimore) ; 99(8): e19191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080103

RESUMO

INTRODUCTION: Chronic neck pain is a common musculoskeletal disorder that is associated with functional disability and decreased of quality of life. Electrophysical agents are commonly used to relieve pain, however the effects of combined use of these agents are little studied. The objective is to investigate the efficacy of photobiomodulation and electrical stimulation to relieve pain, both in isolation and combined. MATERIALS AND METHODS: This a 4-arm randomized placebo-controlled trial with patient and evaluator blinded. This study will be performed in Department of Physical Therapy at Federal University of São Carlos, São Carlos/SP, Brazil. One hundred and forty-four patients with chronic neck pain will be randomized into 4 groups: active photobiomodulation therapy with active electrical stimulation, active photobiomodulation therapy, active electrical stimulation, or placebo treatment. They will receive 10 sessions of treatment. PRIMARY OUTCOME: pain intensity (measured by pain numerical rating scale) posttreatment. SECONDARY OUTCOMES: pain during movement, neck disability, range of motion, pressure pain threshold, temporal summation, conditioned pain modulation, depressive symptoms, pain catastrophizing, quality of life, analgesic intake, and global perceived effect at posttreatment (10 sessions). Pain intensity and global perceived effect will also be measured after 6 weeks randomization. DISCUSSION: The findings of this study might clarify the importance of using the photobiomodulation therapy and transcutaneous electrical nerve stimulation for patients with chronic neck pain. TRIAL REGISTRATION: NCT04020861. https://clinicaltrials.gov/ct2/show/NCT04020861?term=NCT04020861&draw=2&rank=1.


Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Cervicalgia/terapia , Modalidades de Fisioterapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Adolescente , Adulto , Idoso , Analgésicos/administração & dosagem , Dor Crônica , Terapia Combinada , Depressão/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cervicalgia/epidemiologia , Medição da Dor , Qualidade de Vida , Amplitude de Movimento Articular , Adulto Jovem
6.
Internist (Berl) ; 61(3): 270-276, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32030435

RESUMO

BACKGROUND: The treatment of polyneuropathy includes symptomatic therapy of sensory, motor and autonomic dysfunctions. AIM: This article provides an overview of the current treatment recommendations for polyneuropathy, focusing on pain. METHODS: Current treatment guidelines will be discussed based on a literature research. RESULTS: Calcium-channel anticonvulsants gabapentin/pregabalin as well as antidepressants duloxetine and amitriptyline are recommended as first line therapeutics. Alternatively, topical therapeutics can be used in the case of localized disorders. In individual cases, opioids or other antidepressants/anticonvulsants may be effective. Pharmacological treatment is often limited due to adverse events, which affect the central nervous system in particular. DISCUSSION: In general, treatment for polyneuropathy should follow a multimodal concept and include the treatment of other symptoms. When choosing pain medication, comorbidities, patient's age and adverse events need to be taken into consideration. Phenotype-based stratification may support specialized pain therapy and achieve the best medical treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Neuralgia/tratamento farmacológico , Polineuropatias/tratamento farmacológico , Amitriptilina/uso terapêutico , Analgésicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Pregabalina/uso terapêutico
7.
Internist (Berl) ; 61(3): 326-332, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32072189

RESUMO

Migraine has a very high lifetime prevalence with a severe illness-related burden. As a result, extensive long-term and regular treatment is required, which cannot be covered solely by neurologists. This is particularly the case for the long-term monitoring of migraine, which often takes place over several decades. The diagnosis is made using the diagnostic criteria of the International Headache Society (ICHD-3) based on the clinical phenotype. Owing to often complex neurological symptoms, a detailed weighing up of the differential diagnoses is required, which calls for specialist neurological expertise. The same is true for follow-up appointments of more complex therapy issues. Acute therapy with antiemetics, analgesics, and triptans can, so long as it is effective and is administered not longer than 10 days per month, be carried out by the general practitioner or specialist in internal medicine. This is also true for medical prophylactic treatment with dietary supplements, antihypertensive drugs, and tricyclic antidepressants. If this therapy is unsuccessful, prophylactic substances must be used that require more specialized knowledge, which is also reflected in the formal prescription requirements. Neurologists and pain therapists should then be involved in the treatment. This is particularly true for the use of Onabotulinumtoxin A and monoclonal CGRP-(receptor)-antibodies.


Assuntos
Analgésicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cefaleia/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , Analgésicos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/administração & dosagem , Cefaleia/metabolismo , Humanos , Assistência de Longa Duração , Transtornos de Enxaqueca/diagnóstico , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Resultado do Tratamento , Triptaminas/uso terapêutico
8.
Zhongguo Zhen Jiu ; 40(2): 147-51, 2020 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-32100499

RESUMO

OBJECTIVE: To observe the auxiliary analgesic effect of wrist-ankle acupuncture on patients undergoing transforaminal endoscope surgery. METHODS: A total of 64 patients with lumbar disc herniation who underwent percutaneous lateral transforaminal endoscope surgery were randomly divided into an observation group and a control group, 32 cases in each group. The patients in the control group were treated with injection of 1% lidocaine for routine local infiltration anesthesia. The patients in the observation group were treated with wrist-ankle acupuncture at lower 5 area and lower 6 area for 30 min, 5 min before routine local infiltration anesthesia; immediately, 15 min, 30 min after insertion the left-right technique, up-down technique, and rotation technique were applied for six times, respectively. The mean arterial pressure (MAP), heart rate (HR), blood oxygen saturation (SpO2) and pain visual analogue scale (VAS) were compared between the two groups at the time points of intraoperative puncture (T1), circular saw grinding (T2), and placement of working channel (T3). The intention of reoperation was recorded immediately after operation and 24 h after operation. The expectation and treatment credibility scale (ETCS) was used to evaluate the relationship between patients' expectation and efficacy 5 min before operation and immediately after operation. RESULTS: At T2 and T3 during the operation, the MAP and HR in the obserrvation group were lower than those in the control group, while SpO2 was higher than that in the control group (P<0.05). At T1, there was no significant difference of MAP, HR and SpO2 between the two groups (P>0.05). At T2, the peak VAS and average VAS in the observation group were lower than those in the control group (P<0.05), but there was no significant difference at T1 and T3 (P>0.05). The intention of reoperation in the observation group was higher than that in the control group both immediately after operation and 24 h after operation (P<0.05). In the observation group, the scores of each item in ETCS immediately after operation were higher than those 5 min before operation (P<0.05), while in the control group there was no significant difference between immediately after operation and 5 min before operation (P>0.05). The scores of ETCS1, ETCS2 and ETCS3 immediately after operation in the observation group were higher than those in the control group (P<0.05). CONCLUSION: The wrist-ankle acupuncture has positive auxiliary analgesic effect on lumbago during transforaminal endoscope surgery, and strengthens the patients' confidence on the operation effect.


Assuntos
Analgesia por Acupuntura , Tornozelo , Endoscopia , Punho , Analgésicos , Humanos , Coluna Vertebral/cirurgia
9.
Medicine (Baltimore) ; 99(5): e18939, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000411

RESUMO

RATIONALE: Diagnosing and treating refractory cancer pain have become standardized and effective procedures with guidance from the Expert Consensus on Refractory Cancer Pain released in 2017 by the Committee of Rehabilitation and Palliative Care of China. Doxorubicin has been used for perineural injection in the treatment of chronic non-cancer pain owing to its retrograde sensory ganglion resection effect. Our study reports a new fourth-ladder treatment for cancer pain: CT-guided paravertebral doxorubicin injection for patients with refractory cancer pain caused by paraspinal metastasis. PATIENT CONCERNS: A 48-year-old female and a 47-year-old male patients suffered from refractory cancer pain over the past months. They had both undergone surgical tumor resection, chemotherapy, and precision radiotherapy but result in limited analgesic effect. The daily oral morphine dosage was around 60 to 100 mg and rescue analgesic methods had been used at the time. DIAGNOSES: Refractory cancer pain in 2 patients with renal cancer and hepatobiliary adenocarcinoma. INTERVENTIONS: The patients both received computed tomography (CT)-guided 1 mL of 0.5% doxorubicin paravertebral injection at each affected nerve root segments. OUTCOMES: The Visual Analog Scale and Douleur Neuropathique four Questions were used for 6-month follow-up, and the analgesic requirement was also recorded. The patients enjoyed satisfactory analgesia for up to 6 months without adverse reaction. In addition, the oral opioid analgesic doses were significantly reduced after the neurolytic block. LESSONS: The CT-guided paravertebral doxorubicin injection was an effective fourth-step analgesic interventional technology that allowed our 2 patients with refractory cancer pain to maintain satisfactory analgesia. This analgesia method taken at an appropriate stage, according to the latest analgesic concept, results in good analgesia and opioid use reduction. Also, with the imaging guidance, only a small amount of neurolytic agent is needed to achieve analgesia in a precise and safe way.


Assuntos
Analgésicos/administração & dosagem , Dor do Câncer/tratamento farmacológico , Doxorrubicina/administração & dosagem , Dor Intratável/tratamento farmacológico , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X , Dor do Câncer/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Dor Intratável/diagnóstico por imagem , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico
10.
Zhonghua Yi Xue Za Zhi ; 100(5): 363-366, 2020 Feb 11.
Artigo em Chinês | MEDLINE | ID: mdl-32074780

RESUMO

Objective: To investigate the effects of dural puncture epidural technique for labor analgesia on mothers and neonates. Methods: From January to June 2019, one hundred healthy and nulliparous women, scheduled for elective labor analgesia in the Second Affiliated Hospital of Wenzhou Medical University, met inclusion criteriaand were recruitedin this prospective study. The inclusion criteria are as follows: American Society of Anesthesiologists physical statusⅠorⅡ, New York Heart Association gradeⅠorⅡ,150-175 cm in height,50-90 kg in weight and 37-45 weeks of gestation. They were randomly divided into epidural analgesia group(group P, n=50)and dural puncture epidural group(group D, n=50) by using random number table. Parturients in group D received epidural catheterization immediate after successful epidural puncture, while parturients in group P received a single dural puncture into subarachnoid space with a 27 gauge needle (successful puncture: outflow of cerebrospinal fluid) before epidural catheterization. Epidural labor analgesia was performed with epidural infusion of 0.1% ropivacaine plus 0.25 µg/ml sufentanil in both groups. The VAS scores were evaluated at the following time points: before epidural infusion, each uterine contraction within 30 min after infusion, 30 min, 60 min and 90 min after infusion and withdrawal of infusion. Labor process, mode of delivery, cases of increased oxytocin using, effective PCA pressings, sufentanil and ropivacaine dosages, complications of analgesia, neonatal status were recorded, as well. Results: There were no significant differences in labor duration, mode of delivery, analgesia complications (nausea and vomiting, itching, headache after delivery and Bromage score for motor block), deceleration of fetal heart rate and neonatal Apgar score between the two groups (P>0.05). The number of effective PCA pressings, sufentanil dosage, ropivacaine dosage and cases of increased using of oxytocin were significantly more in group P(t=8.663,7.024,6.509,χ(2)=4.159,all P<0.05), with (8.6±2.5) times, (29±4) µg,(105±15) mg,28% in group P, compared with (4.6±2.1) times,(23±4) µg,(88±12) mg,10% in group D, respectively. The first four VAS scores of uterine contraction after analgesia in group P(VAS=7.9±1.1,6.8± 0.9, 5.6±0.8, 4.5±0.8)were significantly higher than those in group D (VAS=6.8±0.7,4.7±0.8,3.5±0.8,2.9±0.7,t=5.966,12.332,13.125,10.643,all P<0.05). The VAS scores at 90 min after analgesia and withdrawal of analgesia (VAS=2.7±0.6, 2.9±0.7) in group P were significantly higher than those in group D (VAS=2.4±0.6, 2.5±0.6, t=2.500, 3.068, all P<0.05). Conclusion: Compared with traditional epidural technique, dural puncture epidural technique can provide a rapid and effective analgesia with less analgesics, but without increasing adverse effects on mother and infant.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Trabalho de Parto , Analgésicos , Anestésicos Locais , Feminino , Humanos , Gravidez , Estudos Prospectivos , Punções
11.
Medicine (Baltimore) ; 99(3): e18830, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011497

RESUMO

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects of chemotherapy. Its main symptoms are pain, paresthesia, and numbness. However, the mechanisms underlying the development of CIPN remain unclear and standard treatments have not been established. Recently, there has been a growing interest in various approaches to overcome the limitations of the existing treatments. This study aims to evaluate the efficacy and safety of the concurrent use of two complementary and alternative therapies: electroacupuncture (EA) and Chuna manual therapy (CMT), with pregabalin, which is the conventional pharmacotherapy for neuropathic pain. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial, which includes 90 patients with colorectal and breast cancer, who developed CIPN. After a 2-week preparation period, the patients are divided into three groups (pregabalin administration group, pregabalin + EA treatment group, and pregabalin + CMT treatment group), treated for approximately 5 weeks and followed-up 4 weeks after treatment. The primary outcome is assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale score (version 4.0) and the secondary outcome is measured using the Quality of Life Questionnaire-CIPN 20-Item Scale (version 3.0) and the quality of life questionnaire (version 3.0) developed by the European Organisation for Research and Treatment of Cancer. Moreover, exploratory efficacy and safety evaluations will be conducted based on the chemotherapy-completion rate and nerve conduction studies.


Assuntos
Terapia por Acupuntura , Analgésicos/uso terapêutico , Antineoplásicos/efeitos adversos , Manipulações Musculoesqueléticas , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Pregabalina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Projetos de Pesquisa
12.
Expert Rev Clin Pharmacol ; 13(2): 135-146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31990596

RESUMO

Introduction: The use of ketamine infusions for chronic pain has surged, with utilization exceeding the proliferation of knowledge. A proposed mechanism for the long-term benefit in chronic pain is that ketamine may alter the affective-motivational component of pain.Areas covered: In this review, we discuss the classification and various dimensions of pain, and explore the effects of ketamine on different pain categories and components. The relationship between ketamine's action at the NMDA receptor, the development of chronic pain, and the its possible role in preventing the persistence of pain are examined. We also summarize animal models evaluating the antinociceptive effects of ketamine and risk mitigation strategies of ketamine-associated side effects.Expert opinion: Although ketamine exerts most of its analgesic effects via the NMDA receptor, recent evidence suggests that other receptors such as AMPA, and active metabolites such as nor-ketamine, may also play a role in pain relief and alleviation of depression. Data from clinical studies performed in patients with chronic pain and depression, and the observation that ketamine's analgesic benefits outlast its effects on quantitative sensory testing, suggest that the enduring effects on chronic pain may be predominantly due ketamine's ability to modulate the affective-motivational dimension of pain.


Assuntos
Analgésicos/administração & dosagem , Dor Crônica/tratamento farmacológico , Ketamina/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Dor Crônica/fisiopatologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo
13.
Chem Biol Interact ; 317: 108941, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926916

RESUMO

m-Trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] is an organoselenium molecule that displays multiple pharmacological actions, including the antinociceptive effect. The current study investigated the (m-CF3-PhSe)2 restorative properties in models of acute and chronic inflammatory pain induced by complete Freund's adjuvant (CFA). Male adult Swiss mice received an intraplantar injection of CFA in the hindpaw and 24 h (acute) or 14 days (subchronic) later they were treated with a single or repeated (m-CF3-PhSe)2 schedule via intragastric route, respectively. The mechanical and thermal hypernociceptive behaviors were assessed by von Frey hair and hot plate tests. Samples of injected paw were collected to evaluate the tissue edema and myeloperoxidase (MPO) activity while cerebral contralateral cortex samples were used to determine the inflammatory proteins content (subchronic protocol). The acute (m-CF3-PhSe)2 administration (1 and 10 mg/kg) reduced the hypernociceptive behavior and both paw thickness and MPO activity induced by CFA injection. In the subchronic protocol, the repeated administration with a low effective dosage of (m-CF3-PhSe)2 reduced the mechanical and thermal hypernociception as well as restored the edema and MPO activity in paw samples. In addition, the repeated treatment schedule mitigated the increase in TNF-α, IL-1ß and COX-2 content in cerebral contralateral cortex induced by CFA injection. Collectively, these data showed that (m-CF3-PhSe)2 presents anti-inflammatory properties, which could be mediated by an interplay between peripheral and central mechanisms of action, reinforcing the potential biological properties of the compound.


Assuntos
Inflamação/induzido quimicamente , Compostos de Organossilício/farmacologia , Dor/induzido quimicamente , Dor/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal/efeitos dos fármacos , Diclofenaco/administração & dosagem , Diclofenaco/farmacologia , Adjuvante de Freund/toxicidade , Inflamação/tratamento farmacológico , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Compostos de Organossilício/administração & dosagem , Medição da Dor , Sintase do Porfobilinogênio/metabolismo , Carbonilação Proteica , Compostos de Sulfidrila/metabolismo
14.
Postgrad Med ; 132(1): 28-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31900074

RESUMO

Interest in and use of topical analgesics has been increasing, presumably due to their potential utility for relief of acute and chronic pain. Topically applied agents with analgesic properties can target peripheral nociceptive pathways while minimizing absorption into the plasma that leads to potential systemic adverse effects.Clinical trials have found 5% lidocaine patches to be effective and well tolerated for the treatment of post-herpetic neuralgia (PHN) with a minimal risk of toxicity or drug-drug interactions. With this patch formulation, the penetration of lidocaine into the skin produces an analgesic effect without producing a complete sensory block. Use of topical lidocaine is supported by clinical practice guidelines, including first-line treatment by the American Academy of Neurology (guidelines retired 2018), the European Federation of Neurological Societies and second-line by the Canadian Pain Society.FDA approved 5% lidocaine patches in 1999, and a 1.8% topical lidocaine system in 2018 - both indicated for the treatment of pain secondary to PHN. The 1.8% system offers a more efficient delivery of lidocaine that is bioequivalent to 5% lidocaine patches, but with a 19-fold decrease in drug load (i.e., 36 mg versus 700 mg) as well as superior adhesion that allows the patch to maintain contact with the skin during the 12-h administration period.Although topical lidocaine formulations have advanced over time and play an important role in the treatment of PHN, a variety of other conditions that respond to topical lidocaine have been reported in the literature including PHN, lower back pain, carpal tunnel syndrome, diabetic peripheral neuropathy, and osteoarthritis joint pain. Other neuropathic or nociceptive pain syndromes may respond to topical lidocaine in select cases and warrant further study. Clinicians should consider local anesthetics and other topical agents as part of their multimodal treatments of acute and chronic pain.


Assuntos
Analgésicos/administração & dosagem , Lidocaína/administração & dosagem , Administração Cutânea , Analgésicos/uso terapêutico , Humanos , Lidocaína/uso terapêutico , Neuralgia/tratamento farmacológico , Adesivo Transdérmico
15.
Med Oral Patol Oral Cir Bucal ; 25(2): e277-e282, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31967979

RESUMO

BACKGROUND: To assess if photobiostimulation (PBS) alleviates pain intensity/duration and swelling after implant surgery. MATERIAL AND METHODS: Sixty subjects (27 male and 33 female, with a mean age of 47,13 8.05 years) were included and randomly assigned to experimental group (implant surgery and photobiostimulation), placebo group (implant surgery and simulated photobiostimulation) and control group (implant surgery only). INCLUSION CRITERIA: subjects older than 20 years, with a healthy oral mucosa and requiring implant surgery. EXCLUSION CRITERIA: pregnancy, history of implant failure, light sensitivity, metabolic deseases, consumption of antibiotics or corticosteroids in the last two weeks, smokers and alcohol drinkers. Patients reported the pain experienced by using a numeric rating scale (NRS) at 2 hours, 6 hours, 12 hours, 24 hours and from day 2 to 7. Swelling score was assessed by linear measurements and type and number of analgesic drugs within each time-point were recorded on a spreadsheet. Data of pain and amount of swelling were compared among the three groups by using the Kruskal-Wallis H Test and post-hoc comparisons tests. RESULTS: Pain in the experimental group was less compared to controls and placebo group, at each time intervals (p < 0.001) as well as the maximum pain score (experimental group: median = 2, interquartile range 2-3; control group: median = 8, interquartile range 3,75-9; placebo group: median = 8, interquartile range 6,25-9). Swelling was almost insignificant in the experimental group (maximum value = 1, interquartile range 0-2,75, at 24 hours) compared with control (maximum value = 6, interquartile range 5-8,75, at 24 hours) and placebo (maximum value = 6, interquartile range 5-8, at 24 hours). Subjects in the experimental group assumed less analgesics compared to both controls and placebo groups. CONCLUSIONS: Photobiostimulation is an effective method to reduce pain intensity/duration and swelling after implant surgery.


Assuntos
Implantes Dentários , Procedimentos Cirúrgicos Bucais , Idoso de 80 Anos ou mais , Analgésicos , Método Duplo-Cego , Feminino , Humanos , Masculino , Dor Pós-Operatória
16.
J Zoo Wildl Med ; 50(4): 868-873, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926517

RESUMO

Blue poison dart frogs (Dendrobates tinctorius azureus) are commonly maintained in zoological institutions and are becoming popular in the pet trade industry. Sedation or light anesthesia is required for safe and effective handling of this species. In this study, the sedative effects of subcutaneously administered alfaxalone-midazolam-dexmedetomidine (AMD) (20, 40, 5 mg/kg, respectively) and ketamine-midazolam-dexmedetomidine (KMD) (100, 40, 5 mg/kg, respectively) were compared in a prospective, randomized, blinded, crossover study in juvenile blue poison dart frogs (n = 10). Both protocols were partially reversed 45 min after administration of either protocol with subcutaneously administered flumazenil (0.05 mg/kg) and atipamezole (50 mg/kg). Heart rate, pulmonic respiratory rate, various reflexes, and behavioral parameters were monitored after drug administration. Both protocols resulted in rapid loss of righting reflex [median (range): AMD, 5 min (5-5 min); KMD, 5 min (5-10 min)]. Time to complete recovery was similar with both protocols (mean ± SD: AMD, 97.5 ± 11.4 min; KMD, 96.5 ± 25.4 min). The AMD protocol resulted in pulmonic respiratory depression, whereas no significant difference in heart rate was found between the two protocols. All frogs were observed eating within 24 hr of chemical restraint. Gastric prolapses occurred in four frogs (AMD 3, KMD 1) that were easily reduced with a cotton-tip application. No other adverse reactions were observed. The results of this study provide two different subcutaneous chemical restraint protocols in juvenile blue poison dart frogs.


Assuntos
Dexmedetomidina/farmacologia , Midazolam/farmacologia , Pregnanodionas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Envelhecimento , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Antídotos/administração & dosagem , Antídotos/farmacologia , Anuros , Sedação Consciente , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Quimioterapia Combinada , Flumazenil/administração & dosagem , Flumazenil/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Midazolam/administração & dosagem , Pregnanodionas/administração & dosagem
17.
J Zoo Wildl Med ; 50(4): 993-996, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926534

RESUMO

Seven anesthesia events were performed over 6 wk on a 1.5-yr-old female okapi (Okapia johnstoni) being managed for a fetlock injury. A combination of butorphanol (B) (median; range) (0.045; 0.031-0.046 mg/kg), medetomidine (M) (0.037; 0.031-0.037 mg/kg), ketamine (K) (0.553; 0.536-1.071 mg/kg), and thiafentanil (T) (0.0045; 0.0040-0.0046 mg/kg) was administered in a padded stall. One dart containing all drugs was used for the first two anesthesias. Subsequently, BM was administered 10 min prior to KT using two darts. Time (median; range) from initial injection to first effects (6; 3-7 min) and recumbency (14; 4-20 min) were recorded. Induction quality with the one-dart protocol was poor or fair and was good or excellent with the two-dart protocol. Following recumbency, the okapi was intubated and ventilated, and physiological parameters were recorded. Anesthesia was consistently achieved with BMKT, but induction was smoother with the staged two-dart approach. Neither resedation nor renarcotization was observed post-reversal.


Assuntos
Antílopes/fisiologia , Butorfanol/farmacologia , Fentanila/análogos & derivados , Ketamina/farmacologia , Medetomidina/farmacologia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestesia/veterinária , Animais , Butorfanol/administração & dosagem , Esquema de Medicação , Espécies em Perigo de Extinção , Feminino , Fentanila/administração & dosagem , Fentanila/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Ketamina/administração & dosagem , Medetomidina/administração & dosagem
18.
Eur J Med Chem ; 188: 111920, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901745

RESUMO

γ-Aminobutyric acid (GABA) uptake transporters are membrane transport proteins that are involved in the pathophysiology of a number of neurological disorders. Some types of chronic pain appear to result from the dysfunction of the GABAergic system. The deficiency of mouse GAT1 transporter (mGAT1) abolishes the nociceptive response, which means that mGAT1 inhibition is an appropriate medical approach to achieve analgesia. The mGAT4 transporter is the second most abundant GAT subtype in the brain; however, its physiological role has not yet been fully understood in the central nervous system. In this study, we examined whether the combination of mGAT1 and mGAT3/mGAT4 inhibition in a single molecule might lead to potentially synergistic effects improving analgesic activity to relieve neuropathic pain. To study this hypothesis, new GABA uptake inhibitors were designed, synthesized, and evaluated in terms of their activity and subtype selectivity for mGAT1-4. Among new functionalized amino acid derivatives of serine and GABA analogs, compounds with preferential mGAT3/4 inhibitory activity were discovered. Two selected hits (19b and 31c) were subjected to in vivo tests. We found a statistically significant antiallodynic activity in the von Frey test in diabetic and oxaliplatin-induced neuropathic pain model. The novel compounds (4-hydroxybutanoic, 4-hydroxypentanoic, and 4-aminobutanoic acid derivatives and serine analogs) provide new insights into the structure-activity relationship of mGAT3/mGAT4 inhibitors and indicate a new direction in the search for potential treatment of neuropathic pain of various origin.


Assuntos
Analgésicos/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Inibidores da Captação de GABA/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Analgésicos/síntese química , Analgésicos/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Proteínas da Membrana Plasmática de Transporte de GABA/química , Inibidores da Captação de GABA/síntese química , Inibidores da Captação de GABA/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/etiologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Neuralgia/induzido quimicamente , Neuralgia/etiologia , Oxaliplatina , Ligação Proteica , Estreptozocina , Relação Estrutura-Atividade
19.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.


Assuntos
Analgésicos/uso terapêutico , Diterpenos/uso terapêutico , Ericaceae/química , Glucosídeos/uso terapêutico , Dor/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Dor/induzido quimicamente , Medição da Dor , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade
20.
Life Sci ; 245: 117348, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31981633

RESUMO

AIMS: Haloperidol is a neuroleptic drug with high affinity towards the σ1 receptor (σ1R), acting as antagonist that decreases neuropathic pain, but has CNS side effects. This work describes the design and synthesis of a novel analog N­(1­benzylpiperidin­4-yl)­4­fluorobenzamide (LMH-2), which produced antihyperalgesic and antiallodynic effects in rats with neuropathy induced by chronic constriction injury of the sciatic nerve (CCI), being more active than gabapentin (The most widely used drug for the treatment of neuropathic pain). MAIN METHODS: LMH-2 was designed as haloperidol analog. Its structure was characterized by spectroscopic (1H and 13C NMR) and spectrometric mass (electronic impact) techniques. Additionally, in silico predictions of pharmacokinetic, pharmacodynamic and toxicological properties were obtained, with promising results. A competitive binding assay using radioligands was employed to evaluate the in vitro affinity for σ1R, whereas in vivo antihyperalgesic and antiallodynic activities were investigated using Wistar rats with CCI. KEY FINDINGS: LMH-2 showed high affinity for σ1R in an in vitro binding assay, with a Ki = 6.0 nM and a high σ1R/σ2R selectivity ratio. Molecular docking studies were carried out to determine the binding energy and to analyze LMH-2-protein interactions. Through an in silico pharmacological consensus analysis, LMH-2 was considered safe for in vivo evaluation. Thus, LMH-2 had dose-dependent antiallodynic and antihyperalgesic activities; its efficacy was comparable to that of gabapentin, but its potency was 2-times higher than this drug. SIGNIFICANCE: LMH-2 administration produced antihyperalgesic and antiallodynic effects by the antagonism of σ1R, suggesting its potential use as an analgesic drug for neuropathic pain.


Assuntos
Analgésicos/síntese química , Benzamidas/síntese química , Haloperidol/análogos & derivados , Nociceptividade/efeitos dos fármacos , Receptores sigma/antagonistas & inibidores , Analgésicos/farmacologia , Animais , Benzamidas/farmacologia , Relação Dose-Resposta a Droga , Hiperalgesia/induzido quimicamente , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Wistar
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