High-Dose Methotrexate Does Not Affect the Pharmacodynamics of Phenobarbital Hypnotic Action but Decreases the Central Nervous System (CNS) Sensitivity to Pentylenetetrazol-Induced Maximal Seizures in Rats

Chemotherapy with high-dose methotrexate (HD-MTX) is often associated with acute neurotoxicity. We determined whether the altered neuronal function after HD-MTX [such as the reduced regional cerebral metabolic glucose rate (rCMRGlc) and slow electroencephalographic pattern] affects the sensitivity of the CNS to centrally acting drugs: the depressant phenobarbital, which reduces rCMRGlc, and the analeptic agent pentylenetetrazol (PTZ), which elevates rCMRGlc. Adult male Sabra rats received an i.v. infusion of MTX, 0.51 mg/min, to induce neurotoxicity or saline solution for 24 hr. Subsequently, MTX-treated and control groups were infused in one experiment with phenobarbital until loss of the righting reflex and in the second experiment with PTZ until the onset of maximal seizures. HD-MTX did not affect the infused hypnotic dose or serum, brain, and cerebrospinal fluid concentrations of phenobarbital at the onset of anesthesia. The convulsive dose and PTZ concentrations in the serum and brain at the onset of maximal seizures were significantly higher in the HD-MTX-treated animals. These outcomes indicate that HD-MTX and the reduced rCMRGlc that follows this treatment do not contribute to the hypnotic action of phenobarbital. On the other hand, treatment with HD-MTX exhibited anticonvulsant properties as evidenced by the reduced CNS sensitivity to PTZ-induced seizures.     

The Effect of Immunosuppression by Total-Body Irradiation on the Pharmacodynamics of Centrally Active Drugs in Rats

The aim of this investigation was to assess whether immunosuppression induced by total-body irradiation (TBI) affects the pharmacodynamics of centrally acting drugs. Female Sabra rats were exposed to a single dose of gamma irradiation (5.3 Gy). Four days later, when both the cellular and the humoral immune responses were impaired, they received an i.v. infusion of either phenobarbital (0.8 mg/min), ethanol (16.3 mg/min), pentylenetetrazol (PTZ; 0.618 mg/min), or theophylline (as aminophylline; 2 mg/min). The infusion was stopped at the onset of the pharmacologic end point—loss of righting reflex for the depressant agents or maximal seizures for the stimulant drugs—and the concentrations of the neuroactive drugs at that point were determined. In the ethanol experiment, blood samples were also taken upon awakening. The radiation-induced immunosuppression significantly decreased the CNS sensitivity to the depressant action of both phenobarbital and ethanol as indicated by the higher CSF phenobarbital concentrations required to induce sleep in the irradiated rats versus controls (156±4 vs 133 ±5 mg/L, respectively; P < 0.05), and the higher serum ethanol concentrations at the onset and offset of sleep in the immunosuppressed group versus control values (4.6±0.2 and 1.68±0.01 vs 3.79±0.17 and 1.32±0.9 mg/mL, respectively; P < 0.04). Exposure to TBI did not alter the pharmacodynamics of the two convulsant drugs (theophylline andPTZ).     

利多卡因辅助局部麻醉在老年外伤性颈胸段脊髓损伤减压手术的应用

目的：探讨利多卡因辅助局部麻醉在老年外伤性颈胸段脊髓损伤减压手术的应用方法与效果。方法：采用前瞻性研究方法,选择2013年2月至2015年12月在我院进行诊治的外伤性颈胸段脊髓损伤老年患者78例,根据入院顺序分为观察组与对照组各39例,两组都给予减压手术治疗,对照组选择全身麻醉,观察组选择利多卡因辅助局部麻醉,观察两组预后情况。结果：两组患者在麻醉前后的收缩压、舒张压、心率未出现明显变化,对比差异均无统计学意义（P>0.05）。观察组术中神经损伤、术后呼吸道不适等并发症发生率与住院时间分别为2.6%和（7.11±0.45d）,而对照组分别为23.1%和（9.33±0.51d）,观察组的两项指标明显低于对照组（P<0.05）。术后观察组与对照组的麻醉满意度分别为100.0%和84.6%,观察组明显高于对照组（P<0.05）。观察组与对照组术后3个月的JOA评分分别为（12.94±2.84）分和（10.49±2.44）分,都明显高于术前的（5.37±1.49）分和（5.42±1.33）分,组间对比差异也有统计学意义（P<0.05）。结论：利多卡因辅助局部麻醉在老年外伤性颈胸段脊髓损伤减压手术的应用具有较好的安全性,能提高麻醉效果,减少并发症的发生,缩短住院时间,促进颈椎功能的恢复。     

罗哌卡因与左旋布比卡因用于腹部手术腰硬联合麻醉效果比较

目的:比较罗哌卡因与左旋布比卡因在腹部手术腰硬联合麻醉中的效果安全性。方法:腰硬联合麻醉的腹部手术患者86例随机分为A、B两组各43例。A组采用罗哌卡因麻醉、B组采用左旋布比卡因麻醉,比较两组患者麻醉效果、各时间点患者血流动力学变化,及药品不良反应发生情况。结果:两组患者感觉阻滞时间比较,差异无统计学意义(P>0.05),而A组术后运动神经恢复时间显著短于B组(P<0.05),Bromege评分也显著低于B组(P<0.05)。两组患者麻醉阻滞起效后SBP、DBP、HR等指标均较麻醉前显著降低(P<0.05),而麻醉结束后两组收缩压(SBP)、舒张压(DBP)、心率(HR)与麻醉前比较,差异无统计学意义(P>0.05)。术中各时间点两组SBP、DBP、HR等指标比较,差异也无统计学意义(P>0.05)。两组药品不良反应发生率比较,差异无统计学意义(P>0.05)。结论:罗哌卡因与左旋布比卡因对患者感觉神经的阻滞作用相当,对患者血流动力学的影响及药品不良反应发生率也基本相同。而罗哌卡因对于运动神经的阻滞作用较弱,更有利于患者术后早期运动。     

Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model

The administration of diluted bee venom (DBV) into an acupuncture point has been utilized traditionally in Eastern medicine to treat chronic pain. We demonstrated previously that DBV has a potent anti-nociceptive efficacy in several rodent pain models. The present study was designed to examine the potential anti-nociceptive effect of repetitive DBV treatment in the development of below-level neuropathic pain in spinal cord injury (SCI) rats. DBV was applied into the Joksamli acupoint during the induction and maintenance phase following thoracic 13 (T13) spinal hemisection. We examined the effect of repetitive DBV stimulation on SCI-induced bilateral pain behaviors, glia expression and motor function recovery. Repetitive DBV stimulation during the induction period, but not the maintenance, suppressed pain behavior in the ipsilateral hind paw. Moreover, SCI-induced increase in spinal glia expression was also suppressed by repetitive DBV treatment in the ipsilateral dorsal spinal cord. Finally, DBV injection facilitated motor function recovery as indicated by the Basso–Beattie–Bresnahan rating score. These results indicate that the repetitive application of DBV during the induction phase not only decreased neuropathic pain behavior and glia expression, but also enhanced locomotor functional recovery after SCI. This study suggests that DBV acupuncture can be a potential clinical therapy for SCI management.     

Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spinal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injections of either BoNT-A (10 U/animal) or saline. At eight weeks post injury, the bladders were collected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI + BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI + saline) (241 ± 25 mg vs. 183 ± 42 mg; p < 0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 μm vs. 193 ± 47.9 μm; p < 0.0001). SCI + BoNT-A animals had significantly thinner bladder walls compared to SCI + saline animals (202 ± 55.4 μm vs. 339 ± 89.0 μm; p < 0.0001). SCI + BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.     

依达拉奉促进大鼠脊髓损伤神经功能恢复作用研究

目的 观察依达拉奉对急性脊髓损伤大鼠神经功能评分的影响，探讨依达拉奉促进大鼠脊髓损伤神经功能恢复的作用。方法 采用改良Allen法制作SD大鼠脊髓中度损伤模型，将模型鼠随机分为实验组和对照组各16只。实验组按3 mg·kg^-1的剂量将依达拉奉用0.9%氯化钠溶液稀释后，每隔12 h腹腔注射1次，给药时间为30 min，共14 d。对照组采用同样方式给予0.9%氯化钠溶液。比较实验开始后不同时间大鼠斜板试验、神经功能评分变化。结果 从伤后2周和3周起，实验组的斜板最大角度和神经功能评分分别与对照组比较均差异有极显著性（均P＜0.01）。结论 依达拉奉对大鼠脊髓损伤神经功能的恢复具有促进作用。     

鞘内注射可乐定对切口痛大鼠脊髓背角PKA催化亚单位表达的影响

目的:观察鞘内注射(intrathecal injection IT)可乐定对切口痛大鼠脊髓背角PKA催化亚单位表达的影响.方法:选择鞘内置管成功的雄性SD大鼠80只,随机分为5组,每组16只,分别为假手术组,对照组,可乐定5μg组,可乐定10μg组和可乐定20μg组.按Yaksh法鞘内置管,按Brennan法制作大鼠...     

探讨前、后路减压治疗胸腰段脊柱骨折合并脊髓损伤的临床对照分析

目的对比分析前、后路减压治疗胸腰段脊柱骨折合并脊髓损伤的临床效果。方法收集我院2011年8月至2013年8月期间诊治的胸腰段脊柱骨折合并脊髓损伤患者66例作为研究对象,以抛硬币的方式分为试验组与对照组,每组患者各33例。对照组患者采用后路减压手术治疗,试验组采用前路减压手术治疗,对两组患者的治疗效果进行分析对比。结果研究结果显示,试验组术后运动评分、触觉评分、伤椎高度、Cobb's角恢复情况明显优于对照组(P<0.05)。结论前路减压手术治疗胸腰段脊柱骨折合并脊髓损伤的临床效果优于后路减压治疗,能有效促进术后运动评分、触觉评分改善及伤椎高度、Cobb's角恢复,值得在临床应用上推广。     

Contribution of TRPV1 Receptor–Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

Neuropathic pain induces allodynia and hyperalgesia. In the spared nerve injury (SNI) model, marked mechanical hyperalgesia is manifested as prolongation of the duration of paw withdrawal after pin stimulation. We have previously reported that spinal ventral root discharges (after-discharges) after cessation of noxious mechanical stimulation applied to the corresponding hindpaw were prolonged in anesthetized spinalized rats. Since these after-discharges occurred through transient receptor potential (TRP) V1–positive fibers, these fibers could contribute to mechanical hyperalgesia. Therefore, we examined whether selective deletion of TRPV1-positive fibers by resiniferatoxin, an ultrapotent TRPV1 agonist, would affect the behavioral changes and ventral root discharges in SNI rats. Mechanical allodynia in the von Frey test, mechanical hyperalgesia after pin stimulation, and enhancement of ventral root discharges, but not thermal hyperalgesia in the plantar test, appeared in Wistar rats with SNI. Mechanical hyperalgesia was abolished by treatment with resiniferatoxin, whereas mechanical allodynia was not affected. Moreover, resiniferatoxin eliminated after-discharges completely. These results show that TRPV1-positive fibers do not participate in the mechanical allodynia caused by sensitization of Aβ-fibers, but contribute to the enhancement of after-discharges and mechanical hyperalgesia following SNI. It is suggested that the mechanisms responsible for generating mechanical allodynia differ from those for prolongation of mechanical hyperalgesia.     

Video-Urodynamic Characteristics and Predictors of Switching from Botulinum Neurotoxin a Injection to Augmentation Enterocystoplasty in Spinal Cord Injury Patients

Botulinum neurotoxin type A (BoNT-A) injection and augmentation enterocystoplasty (AE) are alternative and effective management strategies for neurogenic detrusor overactivity (NDO) refractory to pharmacotherapy. A great majority of patients with spinal cord injury (SCI) may, however, prefer BoNT-A injections to AE, due to the less invasive characteristics. In this study we evaluated the influence of various video-urodynamic study (VUDS) parameters in SCI patients who continuously received repeat BoNT-A detrusor injections or switched to AE to improve their bladder conditions. We compared the changes in the urodynamic parameters before and after each mode of treatment. In this retrospective study, all SCI patients with refractory NDO who had received at least one BoNT-A injection were enrolled. VUDS was performed before and after both BoNT-A injection and AE. All of the urodynamic parameters of the storage and micturition—including the bladder capacity of every sensation, maximal flow rate (Qmax), post-voiding residual volume, detrusor pressure at Qmax, and bladder contractility index—were recorded. A total of 126 patients, including 46 women and 80 men, with a mean age of 41.8 ± 13.1 years, were recruited for this study. All of the patients receiving either BoNT-A injection or AE had a statistically significant increase of bladder capacity at every time-point during filling and a decrease in detrusor pressure at Qmax during voiding. Patients who switched from BoNT-A to AE had greater improvements in their urodynamic parameters when compared with those who continued with BoNT-A injections. Accordingly, SCI patients receiving BoNT-A injections but experiencing few improvements in their urodynamic parameters should consider switching to AE to achieve a better storage function and bladder capacity.