Evaluation of the effect of intrathecal GM1 in 24, 48, and 72 hours after acute spinal cord injury in rats

Abstract Objective The aim of this study was to evaluate the best timing and feasibility of intrathecal application of sodium monosialoganglioside (GM1) after spinal cord contusion in Wistar rats as an experimental model. Methods Forty Wistar rats were submitted to contusion spinal cord injury after laminectomy. The animals were randomized and divided into four groups: Group 1 - Intrathecal application of GM1 24 hours after contusion; Group 2 - Intrathecal application of GM1 48 hours after contusion; Group 3 - intrathecal application of GM1 72 hours after contusion; Group 4 - Sham, with laminectomy and intrathecal application of 0.5 mL of 0.9% saline solution, without contusion. The recovery of locomotor function was evaluated at seven different moments by the Basso, Beattie, and Bresnahan (BBB) test. They were also assessed by the horizontal ladder, with sensory-motor behavioral assessment criteria, pre-and postoperatively. Results This experimental study showed better functional scores in the group submitted to the application of GM1, with statistically significant results, showing a mean increase when evaluated on known motor tests like the horizontal ladder and BBB, at all times of evaluation (p < 0.05), especially in group 2 (48 hours after spinal cord injury). Also, fewer mistakes and slips over the horizontal ladder were observed, and many points were achieved at the BBB scale analysis. Conclusion The study demonstrated that the intrathecal application of GM1 after spinal cord contusion in Wistar rats is feasible. The application 48 hours after the injury presented the best functional results.

Role of intrathecal chemotherapy in the management of meningeal carcinomatosis in patients with breast cancer

ABSTRACT Objective To evaluate whether intrathecal chemotherapy improves clinical outcomes in patients with meningeal carcinomatosis. Methods This retrospective cohort study included consecutive patients with breast cancer diagnosed with meningeal carcinomatosis. Clinical and treatment data were collected from the patients' medical charts. The primary outcome was overall survival, and the secondary outcomes were time to neurological deterioration and reporting of clinical benefit. Logistic regression and Cox proportional hazard models adjusted for potential confounders were used to evaluate the clinical response and overall survival, respectively. Results Overall, 109 female patients were included, 50 (45.9%) of whom received intrathecal chemotherapy with methotrexate and dexamethasone. The median treatment duration was 3 weeks (range, 1-13 weeks). Patients treated with intrathecal chemotherapy were more likely to report clinical benefit (74% versus 57.7%, adjusted odds ratio [OR] = 9.0, 95%CI=2.6-30.9, p<0.001). However, there was no difference in the time to neurologic deterioration (hazard ratio [HR] = 0.96, 95%CI= 0.57-1.59, p=0.86). Patients who received intrathecal chemotherapy did not show an increase in overall survival compared with that of patients who did not receive intrathecal chemotherapy (median overall survival = 1.8 months, 95%CI= 1.27-3.0 versus 2.5, 95%CI= 1.9-3.9, adjusted HR = 0.71, 95%CI= 0.41-1.22, p=0.21). There was a significant interaction between intrathecal chemotherapy and systemic treatment, and patients who received systemic therapy without intrathecal chemotherapy had better overall survival than that of the no-treatment group (adjusted HR = 0.38, 95%CI= 0.20-0.70, p=0.002). Conclusion Intrathecal chemotherapy did not increase overall survival or time to neurological deterioration and should not preclude or postpone systemic treatments.

Effect of intrathecal exosomes derived from human amniotic fluid on neuropathic pain in mice / 中华麻醉学杂志

Objective:To evaluate the effect of intrathecal exosomes derived from human amniotic fluid (hAF exo) on neuropathic pain induced by spared nerve injury (SNI) in mice.Methods:Eighteen clean-grade healthy male Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SNI group, and SNI+ hAF exo group. Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized mice. Another three mice were selected to develop the model of neuropathic pain after anesthesia. PKH-26 labeled hAF exo 7 μl was intrathecally injected on days 1, 2 and 3 after developing the model. The mice were sacrificed at 10 h after the end of administration, and the uptake of hAF exo by the dorsal horn of the injured lumbar enlargement of the spinal cord was observed with the fluorescence microscope. On 1, 2 and 3 days after developing the model, 1 μg/μl hAF exo 7 μl was intrathecally injected in SNI+ hAF exo group, and PBS 7 μl was intrathecally injected in Sham group and SNI group. The mechanical paw withdrawal threshold (MPWT) was measured at 1 day before and 1, 3, 5 and 7 days after operation. And then the mice were sacrificed after measurement of the pain threshold at 7 days after developing the model, and the ipsilateral lumbar enlargement of the spinal cord was taken for determination of the expression of CD11b, interleukin-1beta (IL-1β) and IL-10 by Western blot. Results:The dorsal horn of the lumbar enlargement of the spinal cord on the injured side could absorb hAF exo with the fluorescence microscope. Compared with Sham group, the MPWT was significantly decreased at 3-7 days after developing the model, the expression of CD11b and IL-1β was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10 in SNI group ( P>0.05). Compared with SNI group, the MPWT was significantly increased at 3-7 days after developing the model, the expression of CD11b and IL-1β was down-regulated, and the expression of IL-10 was up-regulated in SNI+ hAF exo group ( P<0.05). Conclusions:Intrathecal exosomes derived from human amniotic fluid can alleviate neuropathic pain in mice, and the mechanism may be related to mediation of the polarization of microglia from M1 type to M2 type and attenuation of neuroinflammation.

Pancytopenia caused by intrathecal injections of chemotherapeutic agents in central nervous system leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Methods:The clinical data of a CNSL patient with pancytopenia caused by intrathecal injections of chemotherapeutic agents in the First Affiliated Hospital of Zhengzhou University in January 2017 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 71-year-old man who was diagnosed with acute myeloid leukemia. During regular chemotherapy, he suffered from extramedullary relapse, and leukemic cells invaded the superior sagittal sinus of brain. Lumbar puncture and intrathecal injections of chemotherapeutic agents were given intermittently. During this period, the complete blood count of patient progressively declined, and oral mucositis appeared. After calcium folinate rescue and intermittent blood transfusion, the complete blood count recovered. Eventually, the patient developed bone marrow relapse and died of infection.Conclusions:On the one hand, the invasion of leukemia cells into the central nervous system leads to increased intracranial pressure and accelerated absorption of cerebrospinal fluid; on the other hand, it induces the structural damage of the superior sagittal sinus or increased permeability, and therefore chemotherapy agents continue to enter the blood with cerebrospinal fluid, which may be the cause of pancytopenia.

A new approach for leptomeningeal metastases: chemotherapy administered through lumbar intrathecal port / Un nuevo abordaje para el tratamiento de las metástasis leptomeníngeas: uso de catéter implantado para el suministro de quimioterapia vía intratecal lumbar

ABSTRACT Background: Intrathecal chemotherapy is a local therapeutic modality used for treatment of leptomeningeal metastases. However, the techniques currently used, i.e. repeated lumbar puncture and Ommaya reservoir, have certain disadvantages. Lumbar intrathecal port (LIP) placement is a relatively novel technique, which has been used for pain management in cancer patients. Objective: To investigate the use of LIP for intrathecal administration of chemotherapeutic agents in patients with leptomeningeal metastases. Methods: Retrospective study of 13 patients treated with intrathecal chemotherapy for secondary leptomeningeal involvement of a primary solid tumor were included in this retrospective study. The patients received intrathecal chemotherapy through a LIP. Results: The patients received a total of 123 intrathecal chemotherapy doses. No grade 3-4 toxicity, technical problem or severe complication developed. During a median of 136 days of follow-up (range, 67-376 days), 12 patients died (92.3%). The treatment resulted in symptom improvement in all patients and self-rated overall health and quality of life improved, compared with baseline. Conclusions: The LIP system, which has been used for intrathecal pain management for decades, appears to offer a safe alternative for intrathecal chemotherapy in patients with leptomeningeal metastases. Further studies are warranted to clarify its potential use in this setting.

RESUMEN Antecedentes: La quimioterapia intratecal es una modalidad terapéutica local utilizada para el tratamiento de metástasis leptomeníngeas. Sin embargo, las técnicas empleadas actualmente, es decir, las punciones lumbares repetidas y el depósito de Ommaya, tienen algunos inconvenientes. La colocación de un puerto intratecal lumbar (LIP) es una técnica relativamente nueva que se ha utilizado para el tratamiento del dolor en pacientes con cáncer. Objetivo: Investigar el uso de LIP para la administración intratecal de agentes quimioterapéuticos en pacientes con metástasis leptomeníngeas. Métodos: Este estudio retrospectivo incluyó un total de 13 pacientes tratados con quimioterapia intratecal por afectación leptomeníngea secundaria de un tumor sólido primario. Los pacientes recibieron quimioterapia intratecal a través de un LIP. Resultados: Los pacientes recibieron un total de 123 dosis de quimioterapia intratecal. No se desarrolló toxicidad de grado 3-4, ni se presentaron problemas técnicos o complicaciones graves. Durante un promedio de 136 días de seguimiento (rango, 67-376 días), murieron 12 pacientes (92,3 %). El tratamiento dio como resultado una mejoría de los síntomas en todos los pacientes. La salud general autoevaluada y la calidad de vida mejoraron en comparación con los valores iniciales. Conclusiones: El sistema LIP que se ha utilizado para el manejo del dolor intratecal durante décadas, parece ofrecer una alternativa segura para la quimioterapia intratecal en pacientes con metástasis leptomeníngeas. Serán necesarios más estudios para determinar su uso potencial en este ámbito.

Comparison among subarachnoid opioid mix for cesarean section - An observational study / Comparación de mezcla de Opioides subaracnoideos para cesárea. Estudio observacional

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.

Effects of intrathecal morphine and fentanyl on IFN-γ levels in hippocampus and plasma of rats with incisional pain / 中华麻醉学杂志

Objective:To evaluate the effects of intrathecal morphine and fentanyl on interferon (IFN)-γ levels in hippocampus and plasma of rats with incisional pain.Methods:Ninety-six healthy male Sprague-Dawley rats in which intrathecal catheters were successfully inserted, weighing 180-220 g, aged 6-8 weeks, were divided into 4 groups ( n=24 each) using a random number table method: normal saline group (group NS), incisional pain group (group P), morphine and fentanyl group (group MF) and morphine and fentanyl with incisional pain group (group MFP). Incisional pain model was established in group P and group MFP.At 20 min before the model was established, a 50 μl mixture of morphine 5 μg/kg and fentanyl 0.25 μg/kg was intrathecally injected in group MF and group MFP, while normal saline 50 μl was injected intrathecally in group NS and group P. At 24 h before establishment of the model (T 0) and at 1, 6, 24, 48 and 72 h after establishment of the model (T 1-5), 6 mice were randomly selected from each group for determination of the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL). The animals were sacrificed and hippocampal tissues and blood samples from the inferior vena cava were collected for determination of IFN-γ levels in hippocampal tissues and plasma (by enzyme-linked immunosorbent assay). Results:Compared with group NS, MWT was significantly decreased and TWL was shortened at T 1-5, and IFN-γ concentration in plasma was decreased at T 2, 3 and T 5 in group P, MWT was increased and TWL was prolonged at T 1-3 in group MF, MWT was decreased and TWL was shortened at T 1-3 in group MFP, and IFN-γ concentration in plasma was decreased at T 2 in MF and MFP groups ( P<0.05). Compared with group P, MWT was increased, TWL was prolonged at T 1-5, and IFN-γ concentration in plasma was increased at T 2, 3 and T 5 in MF and MFP groups ( P<0.05). Compared with group MF, MWT was decreased and TWL was shortened at T 1-4, and IFN-γ concentration in plasma was increased at T 2 and T 3 in MFP ( P<0.05). There was no significant difference in IFN-γ concentration at each time point among the 4 groups ( P>0.05). Conclusion:Intrathecal morphine and fentanyl can increase plasma IFN-γ concentration, and improve peripheral immunosuppression.

Recent advances in biology and management of cancer pain / 中国基层医药

Causes of cancer pain are multifactorial and complex.It is an important challenge for the clinicians on how to control cancer pain effectively.Opioids remain the most effective analgesics used in the treatment of cancer pain.But the adverse effects and potential risks associated with chronic use have been paid attention to in clinical work.It is related to molecular discoveries of opioid action that lead to the development of new opioid analgesic on potential new targets in treating cancer pain.Meanwhile, non-pharmacological treatments such as neuromodulation and minimally invasive interventional techniques play an important role in management of cancer pain.It is summarized in this article about the recent advances in biology and management of cancer pain.

Quimioterapia intratecal: percepções e significados atribuídos por pacientes com câncer hematológico / Intrathecal chemotherapy: perceptions and meanings attributed by patients with hematological cancer / Quimioterapia intratecal: percepciones y signficados atribuidos por pacientes com cáncer hematológico

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.

Effect of intrathecal dexmedetomidine on expression of substance P and c-fos in spinal dorsal horns of rats with visceral pain / 中华麻醉学杂志

Objective To evaluate the effect of intrathecal dexmedetomidine on expression of sub-stance P (SP) and c-fos in the spinal dorsal horns of rats with visceral pain. Methods Thirty-two clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (C group), visceral pain group (VP group), dexmedetomidine group (D group) and dexmedetomidine plus atipamezole group (DA group). VP, D and DA groups received intraperitoneal injection of 0. 9％ acetic acid 10 ml∕kg to establish the model of visceral pain, while group C received the equal volume of normal saline instead. At 10 min before the model was es-tablished, dexmedetomidine 20 μl (1μg∕kg) and dexmedetomidine 1μg∕kg plus atipamezole 1μg∕kg (20μl) were intrathecally injected in D and DA groups, respectively, and the equal volume of normal saline 20μl was given instead in C and VP groups. Visceral pain index ( VPI) was recorded at 1 h after intraperito-neal injection, and then rats were sacrificed, and the dorsal horns of the spinal cord ( L4-6 ) were removed for determination of the expression of SP and c-fos by immunohistochemistry. Results Compared with group C, VPI was significantly increased, and the expression of SP and c-fos was up-regulated in VP, D and DA groups (P<0. 05). Compared with group VP, VPI was significantly decreased, and the expression of SP and c-fos was down-regulated in D and DA groups (P<0. 05). Compared with group D, VPI was signifi-cantly increased, and the expression of SP and c-fos was up-regulated in group DA ( P<0. 05) . Conclusion Intrathecal dexmedetomidine reduces the visceral pain through inhibiting the expression of SP and c-fos in the spinal dorsal horns, which is related to the α2-adrenergic receptor in spinal dorsal horns of rats.

Learning curve of radiology residents during training in fluoroscopy-guided facet joint injections / Curva de aprendizado de residentes em radiologia durante treinamento em punção de articulações facetárias guiada por fluoroscopia

Abstract Objective: To develop a simulator for training in fluoroscopy-guided facet joint injections and to evaluate the learning curve for this procedure among radiology residents. Materials and Methods: Using a human lumbar spine as a model, we manufactured five lumbar vertebrae made of methacrylate and plaster. These vertebrae were assembled in order to create an anatomical model of the lumbar spine. We used a silicon casing to simulate the paravertebral muscles. The model was placed into the trunk of a plastic mannequin. From a group of radiology residents, we recruited 12 volunteers. During simulation-based training sessions, each student carried out 16 lumbar facet injections. We used three parameters to assess the learning curves: procedure time; fluoroscopy time; and quality of the procedure, as defined by the positioning of the needle. Results: During the training, the learning curves of all the students showed improvement in terms of the procedure and fluoroscopy times. The quality of the procedure parameter also showed improvement, as evidenced by a decrease in the number of inappropriate injections. Conclusion: We present a simple, inexpensive simulation model for training in facet joint injections. The learning curves of our trainees using the simulator showed improvement in all of the parameters assessed.

Resumo Objetivo: Desenvolver um simulador para treinamento em punção de articulações facetárias guiada por fluoroscopia e avaliar a curva de aprendizado neste procedimento em um grupo de residentes de radiologia. Materiais e Métodos: Tomando uma coluna lombar humana como modelo, desenvolvemos cinco vértebras lombares feitas de metacrilato e gesso. Essas vértebras foram combinadas para formar um modelo anatômico de coluna lombar. Utilizamos um invólucro de silicone para simular a musculatura paravertebral. O modelo foi colocado dentro do tronco de um manequim de plástico. Recrutamos 12 voluntários dentre residentes de radiologia de nosso departamento. Cada aluno realizou 16 punções de articulações facetárias em nosso simulador em uma única sessão de treinamento. Usamos três parâmetros para avaliar as curvas de aprendizado: tempo de procedimento, tempo de fluoroscopia e qualidade do procedimento, definida pelo posicionamento da agulha. Resultados: As curvas de aprendizado de todos os estudantes mostraram melhora nos tempos de procedimento e fluoroscopia com o treinamento. O parâmetro de qualidade do procedimento também mostrou melhora, definida por decréscimo no número de punções inadequadas. Conclusão: Apresentamos um modelo simulador simples e de baixo custo para treinamento em punção de articulações facetárias. As curvas de aprendizado de nossos estudantes mostraram melhora em todos os parâmetros avaliados.

Efficacy and safety of nalbuphine in preventing the side effect of pruritus induced by intrathecal morphine after cesarean section / 中国医师进修杂志

Objective To assess the efficacy and safety of nalbuphine in preventing the side effect of pruritus induced by intrathecal morphine after cesarean section. Methods Sixty patients aged 18- 35 years with ASAⅠ~Ⅱand undergoing cesarean section with combined spinal-epidural anesthesia were randomly and double blindly divided into two groups. Patients in Group N (30 patients) received nalbuphine 4 mg (2 ml) by intravenous route after clamping of the umbilical cord; Patients in Group P (30 patients) received 0.9% NaCl (2 ml) by intravenous route after clamping of the umbilical cord. The protocol of postoperative analgesia was intrathecal morphine 0.2 mg. The patients were followed up for 4 h , and the vital signs were detected at the time of returning to patient s room (T0), 1 h (T1), 2 h(T2), 3 h(T3) and 4 h(T4) after operation. The VAS scores, pruritus severity scores, time of pruritus onset, Ramsay sedation scores and and other adverse effects were recorded. Results The levels of MAP, SpO2, HR in two groups at T0, T1, T2, T3, T4 had no significant differences (P>0.05). The rate of pruritus severity score 0-1 score in group N was significantly higher than that in group P (χ2=17.4, P=0.00). The VAS scores and the rate of drowsiness, nausea, vomiting, shivering and dizziness in two groups had no significant difference (P>0.05). Conclusions Nalbuphine provides a significant reduction of morphine induced pruritus for patients who received intrathecal morphine analgesia after cesarean section.

Effect of intrathecal CLP257 on bone cancer pain in rats / 中华麻醉学杂志

Objective To investigate the effect of intrathecal CLP257 on the bone cancer pain in rats.Methods Forty adult female Sprague-Dawley rats,weighing 180-200 g,were divided into 4 groups (n=10 each) using a random number table:sham operation group (group S),bone cancer pain group (group BCP),dimethyl sulfoxide (DMSO) group,and CLP257 group.Bone cancer pain was induced by inoculating Walker 256 mammary gland carcinoma cell suspension (about 1× 105cells) 10 μl into the medullary cavity of the left tibia.On 7th-9th days after establishment of the model,5％ DMSO 10 μl was injected intrathecally once a day in group DMSO,and 10 μg/μl CLP257 10 μl was injected intrathecally once a day in group CLP257.The mechanical paw withdrawal threshold (MWT) was measured on 1 day before establishment of the model (T0),on 1st-6th days after establishment of the model (T1-6),and at 4 h after intrathecal administration on 7th-9th days after establishment of the model (T7-9).After the last intrathecal administration,the L4-6 segments of the spinal cord were removed for determination of the expression of potassium chloride cotransporter 2 (KCC2) protein and mRNA by Western blot and fluorescent quantitative real-time polymerase chain reaction,respectively.Results Compared with group S,the MWT was significantly decreased,and the expression of KCC2 protein and mRNA was down-regulated in BCP and DMSO groups,and the MWT was significantly decreased (P＜0.05),and no significant change was found in the expression of KCC2 protein and mRNA in group CLP257 (P＞0.05).Compared with group BCP,the MWT was significantly increased,and the expression of KCC2 protein and mRNA was up-regulated in group CLP257 (P＜0.05),and no significant change was found in the parameters mentioned above in group DMSO (P＞0.05).Conclusion Intrathecal CLP257 can attenuate the bone cancer pain in rats.

Effect of intrathecal cardamonin on diabetic neuropathic pain in rats / 中华麻醉学杂志

Objective To evaluate the effect of intrathecal cardamonin on diabetic neuropathic pain (DNP) in rats.Methods Healthy adult male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were included in the study.Diabetes mellitus was produced by intraperitoneal injection of streptozotocin 60 mg/kg after intrathecal catheterization.When decrease in pain threshold＞50％ of the baseline at 21 days after diabetes mellitus was produced,the induction of DNP was considered successful.Twenty-four rats with DNP were divided into 4 groups (n=6 each) using a random number table:group DNP,rapamycin group (group R),cardamonin 50 μg group (group D50) and cardamonin 100 μg group (group D100).Another 6 healthy age-matched rats were used as normal control (group C).In DNP,R,D50 and D100 groups,dimethyl sulfoxide 10 μl,rapamycin 5 μg and cardamonin 50 μg and 100 μg were intrathecally injected,respectively,once a day for 7 consecutive days starting from 21 days after successful estabiishment of the model.Mechanical paw withdrawal threshold (MWT) was measured before establishment of the model,on 7,14 and 21 days after establishment of the model,and on 1,4 and 7 days after intrathecal injection.The rats were sacrificed after the last MWT measurement,and their L3-5 segments of the spinal cord were removed for determination of the expression of S6K,p-S6K and synapsin Ⅱ by Western blot.Results Compared with group C,MWT was significantly decreased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was up-regulated in group DNP (P＜0.05 or 0.01).Compared with group DNP,MWT was significantly increased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was down-regulated in R,D50 and D100 groups (P＜0.05 or 0.01).Compared with group D50,MWT was significantly increased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was down-regulated in group D100 (P＜0.05).Conclusion Intrathecal cardamonin can relieve DNP in rats,and the mechanism is related to inhibiting spinal mammalian target of rapamycin activity and down-regulating the expression of synapsin Ⅱ.

Effect of intrathecal oxytocin on neuropathic pain in rats / 中华麻醉学杂志

Objective To evaluate the effect of intrathecal oxytocin on neuropathic pain in rats.Methods Thirty-six SPF male Sprague-Dawley rats,aged 4-6 weeks,weighing 100-150 g,were divided into 4 groups (n =9 each) using a random number table:control group (group C),neuropathic pain group (group NP),neuropathic pain plus normal saline group (group NPN) and neuropathic pain plus oxytocin group (group NPO).The neuropathic pain model was made by partial sciatic nerve injury in NP,NPN and NPO groups.In group NPO,oxytocin l0 μl (0.1 μg) was intrathecally injected on the day of establishing the model and 1 and 2 days after establishing the model,and then normal saline 10 μl was given for tube sealing at 9 a.m.and 4 p.m.every day.In group NPN,normal saline 20 μl was given for tube sealing at the corresponding time points.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 1,2,3,4,5,6 and 7 days after establishing the model.The expression of the astrocyte marker glial fibrillary acidic protein (GFAP) and a specific marker of microglia ionized calcium-binding adaptor molecule 1 (IBa-1) was detected by Western blot at 1 day before establishing the model and 3 and 7 days after establishing the model.Results Compared with group C,the MWT was significantly decreased,TWL was shortened and the expression of GFAP and IBa-1 was up-regulated at each time point in NP and NPN groups (P＜0.05).There was no significant difference in MWT,TWL GFAP and IBa-1 at each time point between group NPN and group NP (P＞0.05).Compared with NP group,MWT was significantly increased at 2-4 days after establishing the model,TWL was prolonged at 1-4 days after establishing the model,the expression of IBa-1 was down-regulated on 3 days after establishing the model,and the expression of GFAP was downregulated on 3 and 7 days after establishing the model in group NPO (P＜0.05).Conclusion Oxytocin can reduce neuropathic pain,and the mechanism may be related to inhibiting activation of glial cells in the spinal cord of rats.

Efficacy of intrathecal injection of vancomycin and dexamethasone in treating refractory purulent meningitis in children / 重庆医学

Objective To observe and investigate the efficacy and safety of combining with intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem for treating refractory purulent meningitis in children.Methods Ninety children cases of refractory purulent meningitis from June 2014 to March 2015 were randomized into the observation group (45 cases) and control group (45 cases) according to the random number table method.The control group was given intravenous meropenem therapy,on this basis the observation group was added with intrathecal injection of vancomycin and dexamethasone.The changes of serum inflammatory markers and clinical efficacies after 7 d treatment were compared between the two groups,and the incidence rate of sequelae in the two groups were recorded after 3-months follow up.Results The descend ranges of TNF-a,CRP and PCT after 7 d treatment in the observation group were (87.3±21.8)pg/mL,(47.9±10.7)mg/L and (348.9J67.3)pg/mL,which were significantly higher than (61.5±18.5)pg/mL,(33.0± 7.9)mg/L,(263.7 ± 61.5)pg/mL in the control group(P＜0.05).There was statistically significant difference in clinical efficacy between the two groups (Z=2.086,P=0.037),the total effective rate in the observation group was 93.3 ％,which was higher than 82.2 ％ in the control group (x2 =2.589,P =0.108);the average treatment duration in the observation group was(12.8 ± 3.9)d,which was significantly less than (16.7 ± 4.7)d in the control group,the difference was statistically significant(t=4.216,P＜0.01).There were no statistically significant differences in the incidence rate of adverse drug reactions and sequelae between the two groups (P＞0.05).Conclusion With intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem therapy for treating purulent meningitis,can further inhibit the inflammatory reaction,and increases clinical efficacy without significantly increasing adverse drug reactions.

Effects of tempol administered via different routes on neuropathic pain in rats / 中华麻醉学杂志

Objective To evaluate the effects of tempol administered via different routes on neuropathic pain (NP) in rats.Methods Thirty-two male Sprague-Dawley rats,weighing 250-280 g,aged 8-10 weeks,were randomly divided into 4 groups (n=8 each) using a random number table:sham operation group (group S),group NP,intrathecal tempol group (group T1),and intraperitoneal tempol group (group T2).Neuropathic pain was induced by chronic constriction injury in chloral hydrate-anesthetized rats.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.The sciatic nerve was only exposed but not ligated in group S.After successful establishment of the model,a catheter was inserted at L4.5 interspace into the epidural space.In S and NP groups,0.9％ normal saline 20 μl was injected intrathecally,and 0.9％ normal saline 200 μl was injected intraperitoneally once a day for 7 consecutive days.In group T1,tempol 30 μg (in 20 μl of normal saline) was injected intrathecally,and 0.9％ normal saline 200 μl was injected intraperitoneally once a day for 7 consecutive days.In group T2,tempol 30 μg (in 200 μl of normal saline) was injected intraperitoneally,and 0.9％ normal saline 20 μl was injected intrathecally once a day for 7 consecutive days.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 3 days before operation,and at 1,3,5,7,10 and 14 days after operation.The animals were sacrificed after measurement of pain threshold at day 14 after operation.The lumbar segment of the spinal cord was removed to detect malondialdehyde (MDA) content and superoxide dismutase (SOD) activity by enzyme-linked immunosorbent assay.Results Compared with group S,the MWT was significantly decreased,and the TWL was shortened at each time point after operation,the content of MDA in the spinal cord was increased (P＜0.05),and no significant difference was detected in SOD activity in group NP (P＞0.05).Compared with group NP,the MWT was significantly increased at 5,7,10 and 14 days after operation,the TWL was prolonged at 1,3,5,7,10 and 14 days after operation,the content of MDA in the spinal cord was decreased,and the SOD activity was increased in group T1 (P＜0.05),and no significant change was found in the indexes mentioned above in group T2 (P＞0.05).Conclusion Intrathecal tempol can reduce NP in rats,and the mechanism is related to inhibition of lipid peroxidation in the spinal cord.

Effects of intrathecal low-dose naloxone, morphine and fentanyl on expression of motillin in hippocampus of rats with incisional pain / 中华麻醉学杂志

Objective To evaluate the effects of intrathecal low-dose naloxone,morphine and fentanyl on the expression of motillin (MTL) in the hippocampus of rats with incisional pain.Methods Seventy-two healthy male Sprague-Dawley rats,weighing 180-220 g,aged 6-8 weeks,in which intrathecal catheters were successfully implanted,were randomly divided into 6 groups (n =12 each) using a random number table:normal saline group (NS group),incisional pain group (P group),morphine + fentanyl + incisional pain group (MFP group),and naloxone (0.2,1.0 and 5.0 ng/kg) + morphine + fentanyl groups (MFPN1,MFPN2 and MFPN3 groups).Incisional pain was induced by an incision made into the plantar surface of the right hindpaw.At 20 min before induction of incisional pain,the mixture of morphine 5 μg/kg and fentanyl 0.25 mg/kg was injected intrathecally in group MFP,and the mixture of naloxone 0.2,1.0 and 5.0 ng/kg,morphine and fentanyl were injected intrathecally in MFPN1,MFPN2 and MF-PN3 groups,respectively.Six rats in each group were selected,and the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intrathecal catheterization (T0,baseline),at 24 h before induction of incisional pain (T1),and at 1,3 and 6 h after operation (T2-4).The left 6 rats in each group were selected and sacrificed at 6 h after operation,and the hippocampi,body of the stomach and duodenum were removed for detection of MTL content by enzyme-linked immunosorbent assay.Results Compared with group NS,the MWT was significantly decreased,and the TWL was shortened at T2-4 in P and MFPN3 groups,the MWT was significantly decreased,and the TWL was shortened at T4 in group MFPN1,and the TWL was prolonged at T2 in group MFPN2,the MTL contents in hippocampus and body of the stomach were significantly decreased in P,MFP,MFPN1 and MF-PN3 groups,the MTL contents in duodenum were increased in P and MFPN3 groups,and the MTL contents in duodenum were decreased in MFP and MFPN1 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group MFPN2 (P＞0.05).Conclusion Intrathecal naloxone 1.0 ng/kg combined with morphine and fentanyl can inhibit up-regulation of the expression of MTL in the hippocampus of rats with incisional pain,and then is involved in the maintenance of stable gastrointestinal motility.

Effect of intrathecal methotrexate on activation of spinal astrocytes in a rat model of bone cancer pain / 中华麻醉学杂志

Objective To evaluate the effect of intrathecal methotrexate on activation of spinal astrocytes in a rat model of bone cancer pain (BCP).Methods Sixty female unmated Sprague-Dawley rats,aged 5-7 weeks,weighing 150-180 g,were randomly divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),BCP group (group P),and BCP + methotrexate group (group PM).BCP was induced by injecting Walker-256 cancer cells into the medullary cavity of tibia.On day 7 after BCP,methotrexate 100 μg (diluted to 15 μl in artificial cerebrospinal fluid) was injected intrathecally over 10 s in group PM,and artificial ccrebrospinal fluid 15 μ1 was injected intrathecally over 10 s in S and P groups.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before BCP and 3,7,14 and 21 days after BCP.Five rats were sacrificed after measurement of the pain threshold at 7,14 and 21 days after BCP,and the lumbar enlargement segments of the spinal cord were harvested for detection of the expression of glial fibrillary acidic protein (GFAP) by immuno-histochemistry.Five rats were sacrificed after measurement of the pain threshold at 14 days after BCP,and the expression of GFAP in the spinal cord was detected by Western blot.Results Compared with group S,the MWT was significantly decreased at 3,7,14 and 21 days after BCP in C and CM groups,the expression of GFAP was significantly up-regulated at each time point after BCP in group C,and the expression of GFAP was significantly up-regulated at 7 and 14 days after BCP in group CM (P＜0.05).Compared with group C,the MWT was significantly increased,and the expression of GFAP was significantly down-regulated at 14 and 21 days after BCP in group CM (P＜0.05).Conclusion The mechanism by which intrathecal methotrexate reduces BCP may be related to inhibition of spinal astrocyte activation in the rats.

Effect of intrathecal gastrodin on skin cancer pain in mice / 中华麻醉学杂志

Objective To investigate the effect of intrathecal gastrodin on skin cancer pain in mice.Methods Thirty-two female Balb/c mice,aged 8 weeks,weighing 20-25 g,were randomly divided into 4 groups (n=8 each) using a random number table:sham operation group (group S),skin cancer pain group (group SCP),gastrodin group (group G),and artificial cerebrospinal fluid (ACSF) control group (group ASCF).Skin cancer pain was produced by injecting phosphate buffer solution 20 μl containing about 2 ×105 4T1 breast cancer cells into the plantar surface of the left hindpaw.At 14th day after inoculation of cancer cells,ASCF 5 μl was injected intrathecally in S and ACSF groups,and gastrodin 150 μg/kg (5 μl) was injected intrathecally in group G.Before inoculation,at 30 min before intrathecal injection,and at 15,30,60,90,120 and 150 min after intrathecal injection,the thermal paw withdrawal latency (TWL) was measured.The expression of acid-sensing ion channel (ASIC)-3 mRNA in the spinal dorsal horn was detected using the real-time reverse transcriptase polymerase chain reaction after the last measurement of the pain threshold.Results Compared with group S,the TWL was significantly decreased at each time point before and after intrathecal injection in SCP,ACSF and G groups,and the expression of ASIC-3 mRNA in the spinal dorsal horn was significantly down-regulated in group G (P＜0.05).Compared with group SCP,the TWL was significantly increased at each time point after intrathecal injection,and the expression of ASIC-3 mRNA in the spinal dorsal horn was significantly down-regulated in group G (P＜0.05),and no significant change was found in the parameters mentioned above in group ACSF (P＞0.05).Conclusion Intrathecal gastrodin can reduce skin cancer pain and down-regulate ASIC-3 expression in the spinal dorsal horn which is helpful in maintaining the analgesic effect in mice.