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Rev. colomb. anestesiol ; 49(1): e200, Jan.-Mar. 2021. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1149793


Abstract Introduction Classically, the local anesthetic (LA) has been combined with one lipophilic and another hydrophilic opioid for neuraxial anesthesia in cesarean section. In Colombia, the practice has been the use of morphine hydrochloride with fentanyl, but the occasional shortage of the former triggered an interest in new options. In response to the shortage of morphine in 2017-2018, a contingency plan was developed at the SES Hospital in Caldas, prefilling syringes at the hospital compounding central, with: bupivacaine, morphine and fentanyl (BMF); bupivacaine, fentanyl and hydromorphone (BFH); and bupivacaine and hydromorphone (BH). Hydromorphone has a rapid onset of action, long-lasting effect and is indicated for spinal administration in the safety data sheet; therefore, the advantages of adding fentanyl to this mix are questionable. Objective To compare the clinical analgesic efficacy at the time of the incision and during the first 12 hours after surgery. Methods An observational, analytical study was conducted, using the mixtures BMF, BFH and BH in patients receiving subarachnoid anesthesia for cesarean section. Pain was assessed at the time of the incision, as well as any adverse effects and the pain visual analogue scale over the following 12 hours. Results Of the 71 patients participating in the study, 40.9 % received BMF; 22.5 %, BFH; and 36.6 %, BH. None of the patients experienced pain at the time of the incision. There was no difference in terms of adverse effects among the three groups. The mean difference in the visual analogue scale (VAS) for postoperative pain at 3, 6 and 12 hours was lower in the groups in which hydromorphone was used. Conclusion BFH and BH combinations are comparable to the original preparation in terms of adverse effects, with the advantage of being more effective in controlling postoperative pain.

Resumen Introducción Para anestesia neuroaxial en cesárea, se ha combinado clásicamente el anestésico local (AL) con un opioide lipofílico y otro hidrofílico. En Colombia se ha usado clorhidrato de morfina con fentanilo, pero el ocasional desabastecimiento del primero despertó el interés por nuevas alternativas. En SES Hospital de Caldas se generó un plan de contingencia frente a la escasez de morfina en 2017-2018, pre llenando jeringas en su central de mezclas con: bupivacaína, morfina y fentanilo (BMF); bupivacaína, fentanilo e hidromorfona (BHF); y bupivacaína e hidromorfona (BH). La hidromorfona tiene inicio rápido de acción, efecto prolongado e indicación en ficha técnica por vía espinal, por lo tanto, las ventajas que pudiera generar la adición del fentanilo a esta mezcla son cuestionables. Objetivo Comparar la eficacia analgésica clínica al momento de la incisión y en las primeras 12 horas postoperatorias. Métodos Se realizó un estudio observacional analítico, empleando las mezclas BMF, BHF y BH en pacientes que recibieron anestesia subaracnoidea para cesárea. Se evaluó el dolor a la incisión, los efectos adversos y la escala visual análoga de dolor en las 12 horas siguientes. Resultados De las 71 pacientes del estudio, 40,9 % recibieron BMF; 22,5 %, BHF; y 36,6 %, BH. En ninguna paciente se observó dolor a la incisión. No hubo diferencia en efectos adversos entre los 3 grupos. La diferencia de medias de la escala visual analógica (EVA) para dolor postoperatorio a las 3, 6 y 12 horas, fue menor en los grupos en los que se usó hidromorfona. Conclusiones Las mezclas BHF y BH son equiparables a la preparación tradicional en cuanto a efectos adversos, con la ventaja de ser más efectivas para el control del dolor postoperatorio.

Humans , Female , Pregnancy , Subarachnoid Space , Cesarean Section , Analgesics, Opioid , Injections, Spinal , Analgesics , Anesthesia, Epidural
Rev. méd. Urug ; 37(1): e37108, mar. 2021. tab, graf
Article in Spanish | LILACS, BNUY | ID: biblio-1289845


Resumen: Se realiza una revisión descriptiva sobre la inyección de ácido tranexámico en el espacio subaracnoideo. Se destaca que un error puede tener consecuencias catastróficas sobre el paciente, con un alto porcentaje de mortalidad. Se analizan las posibles causas que pueden llevar a la inyección errónea. Se advierte sobre la existencia de preparaciones de ácido tranexámico de similar apariencia a las de la bupivacaína de uso intratecal. Se describe el cuadro clínico de la complicación, el mecanismo de toxicidad, los tratamientos utilizados, y la evolución de los casos relatados en las referencias encontradas. Se discuten estrategias para evitar la complicación, señalando que la seguridad no debe basarse en la perfección humana, sino en medidas que dificulten cometer errores.

Summary: A descriptive review of tranexamic acid injection in the subarachnoid space is performed. A point is made that this error may have catastrophic consequences on the patient with a high percentage of mortality. Possible causes that can lead to an erroneous injection are analyzed. A warning is made about tranexamic acid preparations being similar in appearance to those of bupivacaine for intrathecal use. The study describes the clinical manifestation of this complication, the toxicity mechanism, treatments used, and the evolution of the cases reported in the references found. Strategies to avoid complications are discussed, pointing out that safety should not be based on human perfection, but on measures that make it difficult for humans to make mistakes.

Resumo: Faz-se uma revisão descritiva sobre a injeção de ácido tranexâmico no espaço subaracnóideo. Ressalta-se que é um erro que pode ter consequências catastróficas para o paciente com um elevado percentual de mortalidade. Faz-se uma análise das possíveis causas que podem levar ao uso equivocado de ácido tranexâmico devido a existência de preparações semelhantes em aparência às da bupivacaína para uso intratecal. Descreve-se o quadro clínico da complicação, o mecanismo de toxicidade, os tratamentos utilizados e a evolução dos casos relatados nas referências encontradas. Discute-se estratégias para evitar complicações, ressaltando que a segurança não deve ser baseada na perfeição humana, mas em medidas que dificultem o erro do ser humano.

Tranexamic Acid , Injections, Spinal/adverse effects , Medical Errors , Subarachnoid Space
J. venom. anim. toxins incl. trop. dis ; 26: e20190070, 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1101267


Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1ß exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1ß in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1ß using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1ß toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1ß may be feasible for drug-induced analgesia, without causing any severe side effects.(AU)

Animals , Mice , Rats , Peptides , Injections, Spinal , Recombinant Proteins , Analgesia , Biochemical Phenomena , Pharmaceutical Preparations
Article in Chinese | WPRIM | ID: wpr-828567


Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.

Anesthesia , Betacoronavirus , Cesarean Section , Coronavirus Infections , General Surgery , Female , Humans , Infant , Injections, Spinal , Pneumonia, Viral , Diagnosis , General Surgery , Pregnancy , Pregnancy Complications, Infectious , General Surgery , Pregnancy Outcome , Preoperative Care
Article in Chinese | WPRIM | ID: wpr-828544


Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.

Anesthesia , Betacoronavirus , Cesarean Section , Methods , Coronavirus Infections , Female , Humans , Infant , Injections, Spinal , Pandemics , Pneumonia, Viral , Pregnancy
Rev. enferm. UERJ ; 27: e44294, jan.-dez. 2019.
Article in Portuguese | LILACS, BDENF | ID: biblio-1097362


Objetivo: analisar os significados e as percepções dos pacientes submetidos à quimioterapia intratecal sobre esse tratamento. Método: estudo descritivo de abordagem quantiqualitativa, desenvolvida com 13 participantes atendidos em uma central de quimioterapia de um hospital universitário do interior de Minas Gerais, entre os anos de 2015 a 2016, cujos dados, obtidos por meio de entrevistas, foram submetidos à análise do discurso do sujeito coletivo. Aprovado pelo Comitê de Ética em Pesquisa da instituição campo do estudo. Resultados: dos dados codificados emergiram cinco discursos: desconhecimento do tratamento, dor, ansiedade, fé e esperança. Conclusão: a quimioterapia intratecal é desconhecida pelos pacientes em tratamento, causando ansiedade, dor e reações adversas as quais trazem prejuízo para a qualidade de vida desses indivíduos. Com isso criam-se mecanismos de enfrentamento da doença por meio da fé e da esperança.

Objective: analyze the meanings and perceptions of patients undergoing intrathecal chemotherapy about this treatment Method: qualitative and descriptive study carried out with 13 participants attended at a Chemotherapy Center of a University Hospital in the interior of Minas Gerais, from 2015 to 2016, whose data were submitted to the analysis of the collective subject discourse. Approved by the Research Ethics Committee of the study development institution. Results: the information obtained through the interviews was coded and five discourses emerged: lack of treatment, pain, anxiety, faith and hope. Conclusion: intrathecal chemotherapy is unknown to patients undergoing treatment, causing anxiety, pain and adverse reactions that impair their quality of life. This creates mechanisms for coping with the disease through faith and hope.

Objetivo: analizar los significados y las percepciones de los pacientes sometidos a quimioterapia intratecal sobre este tratamiento. Método: estudio de enfoque cuantitativo y descriptivo desarrollado con 13 participantes atendidos en un Centro de Quimioterapia de un Hospital Universitario en el interior de Minas Gerais, entre 2015 y 2016, cuyos datos fueron sometidos al análisis del discurso del sujeto colectivo. Aprobado por el Comité de Ética en Investigación de la institución de desarrollo del estudio. Resultados: la información obtenida a través de las entrevistas fue codificada y surgieron cinco discursos: falta de tratamiento, dolor, ansiedad, fe y Esperanza. Conclusión: la quimioterapia intratecal es desconocida para los pacientes sometidos a tratamiento, lo que causa ansiedad, dolor y reacciones adversas que deterioran su calidad de vida. Esto crea mecanismos para hacer frente a la enfermedad a través de la fe y la esperanza.

Humans , Male , Female , Oncology Nursing , Injections, Spinal , Hematologic Neoplasms , Hematologic Neoplasms/drug therapy , Drug Therapy/methods , Epidemiology, Descriptive , Qualitative Research , Drug Therapy
Prensa méd. argent ; 105(8): 443-447, sept 2019. tab
Article in English | LILACS, BINACIS | ID: biblio-1023260


Background: Pain is defined as "unpleasant sensory and sensory experience", associated with actual or potential tissue domage or described in terms of such damage. Objetive: To assess the effect of bupivacaine versus bupivacaine plus intrathecal dexmedetomidine in postoperative pain. Patients and method: An experimental design was made of a controlled clinical trial type, in patients scheduled for lower abdomen surgery or lower extremities. A sample of 60 patients was studied during the period from October 1 to december 15, 2018, who agreed to participate in the study through of signing consent under information. Results: It was observed that the time of the rescue analgesia was prolonged in more than 120 min in the case of dexmedetomidine when compared with bupivacaine (p<0.0001); also VAS scores at the time of analgesia rescue for the group with dexmedetomidine were 3.71 ± 1.27 and in the bupivacaine group of 5.7 ± 1.59, the difference of two pints of the VAS (p= <0.001) was significant, which demonstrates that dexmedetomidine is effective for prolong postoperative analgesia and decrease the analgesia requirements. Conclusions: Dexmedetomidine at a dose of 5 ug associated with bupivacaine administered intrathecally is more Effective in postoperative analgesia compared with this substance alone in abdominal surgery inferior and lower extremities (AU)

Humans , Pain, Postoperative/therapy , Pain Measurement , Injections, Spinal , Bupivacaine/pharmacokinetics , Statistics, Nonparametric , Dexmedetomidine/pharmacokinetics
Rev. bras. anestesiol ; 69(4): 403-412, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1041995


Abstract Background and objectives Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs like (S)-(+)-Ketoprofen, may be effective at lower intrathecal doses than parenteral ones. Preclinical safety regarding possible neurotoxicity associated with the intrathecal (S)-(+)-Ketoprofen was not evaluated. Here we analysed the neurotoxicity of intrathecally administered (S)-(+)-Ketoprofen in rats. Methods A randomized placebo-controlled experimental study was conducted. Sprague-Dawley rats (250-300 g) aged 12-16 weeks were randomly divided into 2 treatments [100 and 800 µg (S)-(+)-Ketoprofen] and control (sterile water) groups. Intrathecal catheters were placed via the atlantoaxial space in anesthetized rats. Pinch-toe tests, motor function evaluations and histopathological examinations of the spinal cord and nerve roots were performed at days 3, 7 and 21. Spinal cord sections were evaluated by light microscopy for the dorsal axonal funiculus vacuolation, axonal myelin loss, neuronal chromatolysis, neuritis, meningeal inflammation, adhesions, and fibrosis. Results Rats in all the groups exhibited normal pinch-toe testing response (score = 0) and normal gait at each observed time (motor function evaluation score = 1). Neurotoxicity was higher with treatments on days 3 and 7 than that on day 21 (2, 3, 0, p = 0.044; 2, 5, 0, p = 0.029, respectively). On day 7, the total scores reflecting neuronal damage were higher in the 800 µg group than those in the 100 µg and Control Groups (5, 3, 0, p = 0.048, respectively). Conclusion Intrathecal (S)-(+)-Ketoprofen caused dose-dependent neurohistopathological changes in rats on days 3 and 7 after injection, suggesting that (S)-(+)-Ketoprofen should not be intrathecally administered.

Resumo Justificativa e objetivos A administração intratecal de anti-inflamatórios não esteroides é mais eficaz no tratamento da dor pós-operatória. Anti-inflamatórios não esteroides, como o (S)-(+)-cetoprofeno, pode ser eficaz em doses intratecais inferiores às parenterais. A segurança pré-clínica relativa à possível neurotoxicidade associada ao (S)-(+)-cetoprofeno intratecal não foi avaliada. Neste estudo avaliamos a neurotoxicidade do (S)-(+)-cetoprofeno administrado por via intratecal em ratos. Métodos Conduzimos um estudo experimental randomizado e controlado por placebo em ratos Sprague-Dawley (250-300 g) com idades entre 12 e 16 semanas. Eles foram randomicamente divididos em dois grupos de tratamento [100 e 800 µg de (S)-(+)-cetoprofeno] e um de controle (água estéril). Cateteres intratecais foram colocados através do espaço atlantoaxial nos ratos anestesiados. Testes de pinça, avaliações da função motora e exames histopatológicos da medula espinhal e das raízes nervosas foram realizados nos dias 3, 7 e 21 do estudo. Os cortes da medula espinhal foram avaliados por microscopia de luz para vacuolização do funículo axonal dorsal, perda de mielina axonal, cromatólise neuronal, neurite, inflamação, aderências e fibrose das meninges. Resultados Em todos os grupos, os ratos exibiram resposta normal ao teste de pinça (pontuação = 0) e marcha normal em cada tempo observado (escore de avaliação da função motora = 1). A neurotoxicidade foi maior com os tratamentos nos dias 3 e 7 do que no dia 21 (2, 3, 0, p = 0,044; 2, 5, 0, p = 0,029, respectivamente). No dia 7, os escores totais refletindo o dano neuronal foram maiores no grupo com 800 µg que nos grupos com 100 µg e controle (5, 3, 0, p = 0,048, respectivamente). Conclusão A administração intratecal de (S)-(+)-cetoprofeno causou alterações neuro-histopatológicas dose-dependentes em ratos nos dias 3 e 7 após a aplicação e sugerindo que o (S)-(+)-cetoprofeno não deve ser administrado por via intratecal.

Animals , Male , Rats , Spinal Cord/drug effects , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Ketoprofen/toxicity , Neurotoxicity Syndromes/etiology , Rats , Time Factors , Injections, Spinal , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ketoprofen/administration & dosage , Rats, Sprague-Dawley , Dose-Response Relationship, Drug
Clinical Pain ; (2): 59-64, 2019.
Article in Korean | WPRIM | ID: wpr-811494


OBJECTIVE: This study evaluated the feasibility of ultrasound-guided lumbar nerve root block (LNRB) and S1 nerve root block by identifying spread patterns via fluoroscopy in cadavers.METHOD: A total of 48 ultrasound-guided injections were performed in 4 fresh cadavers from L1 to S1 roots. The target point of LNRB was the midpoint between the lower border of the transverse process and the facet joint at each level. The target point of S1 nerve root block was the S1 foramen, which can be visualized between the median sacral crest and the posterior superior iliac spine, below the L5-S1 facet joint. The injection was performed via an in-plane approach under real-time axial view ultrasound guidance. Fluoroscopic validation was performed after the injection of 2 cc of contrast agent.RESULTS: The needle placements were correct in all injections. Fluoroscopy confirmed an intra-foraminal contrast spreading pattern following 41 of the 48 injections (85.4%). The other 7 injections (14.6%) yielded typical neurograms, but also resulted in extra-foraminal patterns that occurred evenly in each nerve root, including S1.CONCLUSION: Ultrasound-guided injection may be an option for the delivery of injectate into the S1 nerve root, as well as lumbar nerve root area.

Cadaver , Fluoroscopy , Injections, Spinal , Lumbosacral Region , Methods , Needles , Spinal Nerve Roots , Spine , Ultrasonography , Zygapophyseal Joint
Article in English | WPRIM | ID: wpr-759516


BACKGROUND: Previous studies have shown that sequential intrathecal injection of fentanyl and hyperbaric bupivacaine for cesarean section (CS) anesthesia provides a superior anesthetic effect than use of bupivacaine alone, and prolongs postoperative analgesia. Herein, we investigated whether rapid intrathecal injection of fentanyl followed by slow injection of hyperbaric bupivacaine affects the duration of postoperative analgesia, the effectiveness of anesthesia, and hemodynamic status. METHODS: Fifty-six parturients with American Society of Anesthesiologists physical status I or II, aged 18–40 years, and scheduled to undergo elective CS were randomly assigned to 2 groups of 28 patients each. The normal sequential group received sequential intrathecal injections of fentanyl and hyperbaric bupivacaine at the same rate, each with a 5 ml syringe. The rapid sequential group received a rapid intrathecal injection of fentanyl with an insulin syringe, followed by a slow injection of hyperbaric bupivacaine with a 5 ml syringe. The onset of sensory block, the timing of the first rescue analgesia, the doses of rescue analgesics, the degree of postoperative pain, the onset and duration of motor block, the incidence and duration of hypotension, and spinal anesthesia-related complications were recorded. RESULTS: While both approaches had comparable spinal anesthesia-related complications, incidence and duration of hypotension, and doses of ephedrine, the rapid sequential group exhibited a more rapid onset of sensory block, a higher sensory level, and more prolonged postoperative analgesia. CONCLUSIONS: Rapid sequential injection of fentanyl and hyperbaric bupivacaine produced superior anesthesia and more prolonged postoperative analgesia than sequential injections of both at the same rate.

Analgesia , Analgesics , Anesthesia , Anesthesia, Spinal , Anesthetics , Bupivacaine , Cesarean Section , Ephedrine , Female , Fentanyl , Hemodynamics , Humans , Hypotension , Incidence , Injections, Spinal , Insulin , Pain, Postoperative , Pregnancy , Syringes
Article in English | WPRIM | ID: wpr-763021


There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Animals , Computational Biology , Constriction , Down-Regulation , Hyperalgesia , Inflammation , Injections, Spinal , Mice , MicroRNAs , Neuralgia , p38 Mitogen-Activated Protein Kinases , Phosphotransferases , Protein Kinases , Rats , Sciatic Nerve , Spinal Cord , Up-Regulation
Article in Korean | WPRIM | ID: wpr-786061


STUDY DESIGN: Review article.OBJECTIVES: To assess the evidence for nonoperative treatment of various degenerative spinal degenerative diseases.SUMMARY OF LITERATURE REVIEW: No study has yet evaluated the evidence for preoperative nonoperative treatment of lumbar spinal diseases.METHODS: The evidence regarding nonoperative treatment for each disease was reviewed through NASS guidelines, and the treatment effect compared to surgical treatment was reviewed through the SPORT series. The efficacy of nonoperative treatment according to disease severity and certain special conditions was investigated through corresponding individual articles.RESULTS: No kind of nonoperative treatment could change the fundamental progression of degenerative spinal disease. The natural course of lumbar disc herniation is favorable regardless of treatment. More than 70% of routine cases improve within 6 weeks. However, it does not take a full 6 weeks to decide whether to perform surgery or not. The evidence for transforaminal epidural steroid injections for short-term pain control is grade A. There is grade B evidence for nonoperative treatment with the goal of mid- to long-term pain control. However, we cannot say that those outcomes are better than the natural course of the disease itself. In cases of radicular weakness, the degree of weakness is correlated with the final outcomes, but it is not evident whether the duration of weakness is correlated with surgical outcomes. Early surgery is usually necessary due to intolerable pain, rather than stable motor weakness. The social cost of herniated discs arises from the loss of patients’ productivity, rather than from direct medical expenses. The natural course of spinal stenosis involves provoked pain and the need for palliative care. Unlike disc herniation, rapid deterioration and marked improvement do not occur. The symptoms of mild to moderate lumbar stenosis are unchanged in 70% of cases, improve in 15%, and worsen in 15%. No study has compared nonoperative treatment with the natural course of the disease. There is no evidence for nonoperative treatment of severe stenosis. Epidural spinal injections are effective for controlling short-term pain. Spontaneous recovery of radicular weakness does not occur, and urgent surgery is necessary in such cases. There is no evidence regarding the natural course and nonoperative treatment of degenerative spondylolisthesis. The working group consensus recommends that it should follow the pattern of nonoperative treatment of spinal stenosis when radicular stenosis symptoms are predominant. Overall, 40%–66% of cases of adult bilateral isthmic spondylolysis progress to symptomatic spondylolisthesis. No studies have investigated nonoperative treatment except physical exercise.CONCLUSIONS: Although short-term symptom amelioration can be achieved by nonoperative treatment, the fundamental progression of the disease is not affected. For conditions excluded from most studies, such as prior spine surgery, cauda equina syndrome, progressive neurological deficit, and uncontrollable severe pain associated with instability, deformity, or vertebral fractures, there were not enough studies to reach informed conclusions. Our review found no evidence regarding nonoperative treatment for such conditions. Furthermore, the treatment methods for each disease are not clearly distinguished from each other, and the techniques used for disc herniation have been applied to other diseases without any evidence.

Adult , Congenital Abnormalities , Consensus , Constriction, Pathologic , Efficiency , Exercise , Humans , Injections, Spinal , Intervertebral Disc Displacement , Palliative Care , Polyradiculopathy , Spinal Diseases , Spinal Stenosis , Spine , Spondylolisthesis , Spondylolysis , Sports
Article in Chinese | WPRIM | ID: wpr-813291


To explore whether Wnt3a exerts a role in neuropathic pain through Jumonji C domain 6 (JMJD6)-associated epigenetic modification. 
 Methods: SD rats were divided into 4 groups: A sham group, a chronic constriction injury (CCI) group, a CCI+negative lentiviral expression vector (LV-NC) group and a CCI+lentiviral overexpression vector (LV-JMJD6) group. The sciatic nerve CCI model of SD rat and JMJD6 lentiviral expression vector were constructed. On the third day after CCI, the intrathecal catheter was prepared, and 20 μL of normal saline and lentivirus-containing reagent (virus titer 1×108 TU/mL) were administered. The rats' paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were monitored, and Western blotting was used to detect the expression of Wnt3a and NR2B protein in the spinal cord. Co-immunoprecipitation was applied to detect the interaction between JMJD6 and Wnt3a.
 Results: Compared with the sham group, the PWMT of the rats in each group after CCI was significantly decreased and the PWTL was significantly shortened (P<0.05). Compared with the CCI group and the CCI+LV-NC group, PWMT in the CCI+LV-JMJD6 group was increased significantly on the 10th day and the 14th day after CCI, and the PWTL was significantly prolonged on the 14th day after CCI (P<0.05). On the 14th day after CCI, the expression levels of Wnt3a and NR2B in the CCI group and the CCI+LV-NC group were significantly higher than those in the sham group. After intrathecal injection of lentiviral vector, Wnt3a and NR2B protein expression levels in the CCI+LV-JMJD6 group were lower compared with the CCI+LV-NC group (P<0.05). The results of co-immunoprecipitation showed no direct interaction between Wnt3a and JMJD6.
 Conclusion: Wnt3a is involved in mediating neuropathic pain, and its effect may be related to the epigenetic modification of JMJD6, which is likely regulated through indirect interaction.

Animals , Injections, Spinal , Neuralgia , Rats , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord , Wnt3A Protein
Article in English | WPRIM | ID: wpr-761920


BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.

Animals , Biochemistry , Body Weight , Bone Marrow , Brain , Cell- and Tissue-Based Therapy , Culture Media , DNA , Friedreich Ataxia , Heart , Hematology , Humans , Injections, Spinal , Mesenchymal Stem Cells , Methods , Mice , Neurodegenerative Diseases , Neuroprotection , Reference Values , Severe Combined Immunodeficiency , Spinal Cord
Arq. neuropsiquiatr ; 76(11): 736-742, Nov. 2018. graf
Article in English | LILACS | ID: biblio-973938


ABSTRACT Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the central or peripheral nervous system. Electroacupuncture (EA) has an antinociceptive effect on neuropathic pain, which is partially due to inhibiting astrocyte activation in the spinal cord. We found that an intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, reversed the antinociceptive effects of EA in a chronic constriction injury-induced neuropathic pain model. The expression of GFAP in L4-L6 spinal cord was significantly upgraded, while DPCPX suppressed the effect of the EA-mediating inhibition of astrocyte activation, as well as wiping out the EA-induced suppression of cytokine content (TNF-α). These results indicated that the adenosine A1 receptor is involved in EA actions during neuropathic pain through suppressing astrocyte activation as well as TNF-α upregulation of EA, giving enlightenment to the mechanisms of acupuncture analgesia and development of therapeutic targets for neuropathic pain.

RESUMO A dor neuropática é uma condição de dor crônica causada por dano ou disfunção do sistema nervoso central ou periférico. A eletroacupuntura (EA) tem um efeito antinociceptivo durante a dor neuropática, que é parcialmente devido à inibição da ativação de astrócitos na medula espinhal. Descobrimos que a injeção intratecal de 8-ciclopentil-1,3-dipropilxantina (DPCPX), um antagonista seletivo do receptor de adenosina A1, reverteu os efeitos antinociceptivos da EA no modelo de dor neuropática induzida por lesão por constrição crônica (CCI). A expressão da GFAP na medula espinal L4-L6 foi significativamente melhorada, enquanto a DPCPX suprimiu o efeito da inibição mediadora da EA na ativação de astrócitos, bem como eliminou a supressão induzida pela EA do conteúdo de citocina (TNF-α). Esses resultados indicam que o receptor de adenosina A1 está envolvido nas ações da EA durante a dor neuropática, suprimindo a ativação astrocitária, bem como o aumento da TNF-α na EA, fornecendo esclarecimentos sobre os mecanismos de analgesia da acupuntura e o desenvolvimento de alvos terapêuticos para dor neuropática.

Animals , Male , Rats , Spinal Cord/drug effects , Xanthines/pharmacology , Electroacupuncture/methods , Astrocytes/metabolism , Receptor, Adenosine A1/metabolism , Neuralgia/therapy , Sciatic Nerve/injuries , Spinal Cord/metabolism , Xanthines/administration & dosage , Injections, Spinal , Astrocytes/drug effects , Rats, Sprague-Dawley , Receptor, Adenosine A1/administration & dosage , Disease Models, Animal
Rev. méd. Chile ; 146(6): 802-807, jun. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961462


Intrathecal chemotherapy may be complicated with the development of myelopathies or toxic radiculopathies. This myeloradicular involvement, of toxic character, is unpredictable, since these patients have repeatedly received Intrathecal chemotherapy with the same drugs without apparent injury. The toxic effect should be mainly attributed to Cytarabine and not to methotrexate, since the central nervous system lacks Cytidine deaminase, the enzyme that degrades Cytarabine. We report two patients, an 18-year-old woman and a 16 years old male, who received systemic and intrathecal chemotherapy (methotrexate, cytarabine) for the treatment of an acute lymphoblastic leukemia and developed, in relation to this procedure, a spinal subacute combined degeneration. They had a proprioceptive and motor alteration of the lower extremities and neuroimaging showed selective rear and side spinal cord hyper intensity produced by central axonopathy. Two weeks later the woman developed a quadriplegia and the young man a flaccid paraplegia due to added root involvement.

Humans , Female , Adolescent , Methotrexate/adverse effects , Cytarabine/adverse effects , Subacute Combined Degeneration/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antimetabolites, Antineoplastic/adverse effects , Injections, Spinal , Magnetic Resonance Imaging , Methotrexate/administration & dosage , Fatal Outcome , Cytarabine/administration & dosage , Subacute Combined Degeneration/diagnostic imaging , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Antimetabolites, Antineoplastic/administration & dosage
Arq. neuropsiquiatr ; 76(4): 265-272, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-888378


ABSTRACT Spinal muscular atrophy (SMA) is a severe and clinically-heterogeneous motor neuron disease caused, in most cases, by a homozygous mutation in the SMN1 gene. Regarding the age of onset and motor involvement, at least four distinct clinical phenotypes have been recognized. This clinical variability is, in part, related to the SMN2 copy number. By now, only supportive therapies have been available. However, promising specific therapies are currently being developed based on different mechanisms to increase the level of SMN protein; in particular, intrathecal antisense oligonucleotides that prevent the skipping of exon 7 during SMN2 transcription, and intravenous SMN1 insertion using viral vector. These therapeutic perspectives open a new era in the natural history of the disease. In this review, we intend to discuss the most recent and promising therapeutic strategies, with special consideration to the pathogenesis of the disease and the mechanisms of action of such therapies.

RESUMO A atrofia muscular espinhal (AME) é uma grave doença dos neurônios motores, de grande variabilidade clínica e causada na maioria dos casos por mutação em homozigose no gene SMN1. Pelo menos quatro fenótipos clínicos distintos são reconhecidos com base na idade de início e no grau de envolvimento motor. Tal variabilidade clínica é em parte relacionada com o número de cópias do gene SMN2. Até recentemente, apenas terapias de suporte estavam disponíveis. Atualmente, terapias especificas estão sendo desenvolvidas com base em diferentes mecanismos para aumentar o nível de proteína SMN; em particular oligonucleotídeos antissenso por via intratecal e inserção de cópia do gene SMN1, via endovenosa, usando vetor viral. Nesta revisão, objetivamos discutir as mais recentes e promissoras estratégias terapêuticas, com consideração especial aos aspectos patogênicos da doença e aos mecanismos de ação de tais terapias.

Humans , Oligonucleotides/administration & dosage , Muscular Atrophy, Spinal/therapy , Genetic Therapy/methods , DNA, Antisense/administration & dosage , Survival of Motor Neuron 1 Protein/administration & dosage , Phenotype , Injections, Spinal , Mutation
Rev. chil. infectol ; 35(3): 321-325, 2018. tab
Article in Spanish | LILACS | ID: biblio-959448


Resumen El uso de colistina por vía intratecal se ha consolidado como una opción terapéutica para el manejo de infecciones del sistema nervioso central causadas por bacilos gramnegativos multi-resistentes. La evidencia del éxito terapéutico y del perfil de seguridad es creciente, particularmente en infecciones por Acinetobacter baumanii multi-resistente en adultos. La evidencia en niños es escasa. Se presenta el caso clínico de una niña de 11 años de edad, con una ventriculitis post-quirúrgica por Pseudomonas aeruginosa extensamente resistente tratada con colistina intravenosa e intratecal. Se revisa su uso en niños con meningitis nosocomial causada por bacilos gramnegativos multi-resistentes.

Use of Intrathecal colistin has increased in recent years and has become an alternative for the management of infections of the central nervous system caused by multidrug resistant (MDR) bacteria. Evidence of therapeutic success and safety profile is increasing, particularly in MDR Acinetobacter baumanii infections in adults. Conversely, evidence in children is limited. We present a case of an 11-year-old female with postsurgical meningitis caused by an extensively resistant Pseudomonas aeruginosa strain and treated with venous and intrathecal colistin. The evidence of its use in children with nosocomial meningitis by MDR Gram negative bacteria is reviewed.

Humans , Female , Child , Pseudomonas Infections/drug therapy , Colistin/administration & dosage , Cerebral Ventriculitis/drug therapy , Anti-Bacterial Agents/administration & dosage , Postoperative Complications , Pseudomonas aeruginosa/isolation & purification , Injections, Spinal , Brain Neoplasms/surgery , Cerebral Ventriculitis/microbiology
Article in English | WPRIM | ID: wpr-718570


PURPOSE: Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. METHODS: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively. RESULTS: Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs. CONCLUSIONS: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

Adult , Animal Experimentation , Animals , Asian Continental Ancestry Group , Baths , Excitatory Postsynaptic Potentials , Humans , In Vitro Techniques , Inhibitory Postsynaptic Potentials , Injections, Spinal , Lower Urinary Tract Symptoms , Male , Nerve Fibers, Unmyelinated , Neurons , Prazosin , Prostatic Hyperplasia , Rats , Rats, Sprague-Dawley , Reflex , Spinal Cord , Substantia Gelatinosa , Urinary Bladder , Urination
National Journal of Andrology ; (12): 104-108, 2018.
Article in Chinese | WPRIM | ID: wpr-775212


Objective@#To explore the feasibility and practicability of establishing a rat model of premature ejaculation (PE) by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments.@*METHODS@#Twenty-four male Wistar rats were equally randomized into a PE model and a blank control group. The PE model was established by injection of 8-OH-DPAT in 10 ml normal saline at 0.8 mg per kg of the body weight per day into the subarachnoid space of the lumbosacral spinal cord segments and the control rats were injected with the same volume of normal saline only, both for 4 weeks. Another 24 female Wistar rats were injected subcutaneously with benzoic acid estradiol at 20 μg to induce estrus at 36 hours before mated with the male animals. At 2 and 4 weeks, the male rats were mated with the female ones for 30 minutes each time and meanwhile observed for their mating behavior indicators, such as mount latency, intromission latency, ejaculation latency, mount frequency, intromission frequency, and ejaculation frequency.@*RESULTS@#Compared with the controls, the PE model rats showed a significantly lower ejaculation latency ([712.35 ± 36.77] vs [502.35 ± 46.72] s, P0.05).@*CONCLUSIONS@#A rat model of premature ejaculation was successfully established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments, which is of great significance for further study of the mechanism of premature ejaculation.

8-Hydroxy-2-(di-n-propylamino)tetralin , Animals , Benzoic Acid , Disease Models, Animal , Ejaculation , Estradiol , Estrus , Feasibility Studies , Female , Injections, Spinal , Male , Premature Ejaculation , Rats , Rats, Wistar , Sexual Behavior, Animal , Spinal Cord , Subarachnoid Space