Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.     

Experimentally induced masseter-pain changes masseter but not sternocleidomastoid muscle-related activity during mastication

The aim of this study was to verify the effects of induced masseter-muscle pain on the amplitude of muscle activation, symmetry and coactivation of jaw- and neck-muscles during mastication. Twenty-eight male volunteers, mean age ± SD 20.6 ± 2.0 years, participated in this study. Surface electromyography of the masseter and sternocleidomastoid (SCM) muscles was performed bilaterally during mastication of a gummy candy before and after injections of monosodium glutamate solution and isotonic saline solution. As a result, we observed a decrease in the amplitude of activation of the masseter muscle on the working side (p = 0.009; d = 0.34) and a reduction in the asymmetry between the working and the balancing side during mastication (p = 0.007; d = 0.38). No changes were observed either on the craniocervical electromyographic variables. In conclusion, experimentally induced pain reduced the masseter muscle activation on the working side, thereby reducing the physiological masseters’ recruitment asymmetry between the two sides during mastication. No effects on SCM activity were detected. These results may partly explain the initial maladaptative changes underlying TMD conditions.     

镍钛形状记忆合金环抱器内固定术对多发性肋骨骨折患者术后疼痛、呼吸功能及肺部感染的影响

目的:探讨多发性肋骨骨折患者采用镍钛形状记忆合金环抱器内固定术治疗的临床效果。方法:选取2016年1月-2018年1月期间我院收治的97例多发性肋骨骨折患者。按照不同的治疗方法将患者分为对照组(n=47)和研究组(n=50),对照组患者给予胸部护板外固定术,研究组患者给予镍钛形状记忆合金环抱器内固定术。比较两组患者术后7 d的临床疗效,比较两组术前、术后7 d疼痛程度及呼吸功能情况,记录两组术后并发症发生情况。结果:研究组患者治疗后总有效率为92.00%(46/50),高于对照组患者的76.60%(36/47)(P0.05)。两组患者术后7 d视觉疼痛模拟评分量表(VAS)评分均较术前降低,且研究组低于对照组(P0.05)。两组患者术后7 d最大自主通气量占预计值百分比(MVV%)较术前升高,且研究组高于对照组(P0.05);两组患者术后7 d第1秒用力呼气肺活量占预计值百分比(FEV1%)比较无差异(P0.05)。研究组患者术后并发症总发生率8.00%(4/50),低于对照组的23.40%(11/47)(P0.05)。结论:多发性肋骨骨折经镍钛形状记忆合金环抱器内固定术治疗安全、有效,可明显减轻患者术后疼痛及改善呼吸功能,临床应用价值较高。     

外源性的电磁干预对神经病理性疼痛大鼠的镇痛效果研究

目的:探讨外源性的电磁干预方法对神经病理性疼痛大鼠的镇痛效果。方法:将30只成熟的雄性SD大鼠随机等分成3组:空白对照组(Control),坐骨神经慢性压迫损伤(CCI)组以及坐骨神经慢性压迫损伤协同电磁刺激组(CCI+EMF)。CCI组和CCI+EMF组的20只大鼠建立坐骨神经慢性压迫损伤模型,CCI+EMF组大鼠行外源性的全身性电磁刺激干预(脉冲波形,频率15 Hz,强度30 Gs),每天刺激6小时。在CCI模型构建的第0、3、6、9、12及15天对大鼠测试和比较足底机械痛阈值、足底热痛阈值、运动功能评分和神经传导速率。结果:CCI组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率从CCI手术后的第3天即出现显著性降低,其6、9、12、15天足底机械痛阈值、足底热痛阈值及感觉神经传导速率均显著低于Control组(P0.01),而运动功能评分均显著高于Control组(P0.05)。CCI+EMF组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率在第9、12、15天显著高于CCI组大鼠(P0.05),而运动功能评分均显著高于CCI l组。结论:外源性的电磁刺激对于神经病理性疼痛大鼠具有良好的镇痛效果,有望成为一种临床治疗神经病理性疼痛的新的物理治疗手段。     

剑突肋缘下三孔式胸腔镜下胸腺切除治疗重症肌无力的早期临床疗效及对生活质量的影响

目的:通过与传统单侧胸腔镜技术对比,探讨经剑突肋缘下三孔式胸腔镜下胸腺切除治疗重症肌无力的早期临床疗效及对患者生活质量的影响。方法:收集2012年1月-2016年6月因重症肌无力就诊于我院行胸腔镜下胸腺切除的115例患者。根据患者的手术方式分为传统单侧胸腔镜组47例和剑突肋缘下三孔式胸腔镜组68例,收集和比较两组患者的基本资料,包括性别、年龄、是否合并胸腺瘤、病程、随访时间、术前Osserman评分、手术时间、术中出血量、术后引流时间、术后引流量、转入ICU时间、术后住院时间、术后并发症的发生情况、术后不同时间点的疼痛评分和生活质量评分及末次随访时的愈后情况。结果:两组患者的年龄、性别比例、胸腺瘤情况、病程、随访时间和术前Osserman评分均没有差异(P0.05)。三孔组手术时间、术中出血量、ICU停留时间和术后住院时间均短于或低于传统组(P0.05)。两组患者术后并发症(膈神经麻痹、胸腔积液、伤口脂肪液化)发生率比较没有统计学差异(P0.05)。三孔组患者在术后3天内和出院时的疼痛评分均显著低于传统组(P0.05)。两组患者在末次随访时的有效率、术前、术后1年和末次随访时的生活质量评分(MGQOL-15评分)比较差异无统计学意义(P0.05)。在三孔组患者末次随访时,女性MGQOL-15评分改善量(11.2±3.3分)高于男性(7.4±2.7分)(P0.001)。Osserman评分3分和4分的患者MGQOL-15评分改善量(10.7±3.7分)显著高于Osserman评分2分的患者(5.0±1.9分)(P0.001)。结论:经剑突肋缘下三孔式胸腔镜下切除胸腺治疗重症肌无力具有手术时间短、术中出血少、术后恢复快的特点,术后患者疼痛程度轻,生活质量改善明显。女性术后获益较男性更大。     

不同量表用于机械通气新生儿急性疼痛评估的价值分析

目的:分析和比较不同量表用于机械通气新生儿急性疼痛评估的价值。方法:使用总结性、回顾性研究方法,研究时间为2017年3月份到2018年7月份,选择在医院NICU接受机械通气诊治的新生儿56例作为研究对象,所有新生儿都给予高频震荡通气治疗,急性疼痛采用新生儿疼痛/激惹与镇静量表、新生儿急性疼痛评估量表进行评估与分析,记录评估效果。结果:新生儿疼痛/激惹与镇静量表的总体Cronbachα系数为0.698分,最高评分为基础行为状态,最低评分为心率增快。新生儿急性疼痛评估量表的内部一致性总体Cronbachα系数为0.822,最高评分为胎龄,最低评分为SaO2。新生儿疼痛/激惹与镇静量表的护理人员一致性组内相关系数(ICC)为0.992,新生儿急性疼痛评估量表的护理人员一致性组内相关系数ICC为0.987。以新生儿疼痛/激惹与镇静量表作为效标,新生儿急性疼痛评估量表的效标关联效度Spearman相关系数为r=0.855,P=0.007。12名护理人员对新生儿急性疼痛评估量表的选择率为66.7%,对新生儿疼痛/激惹与镇静量表的选择率为33.3%。结论:新生儿疼痛/激惹与镇静量表和新生儿急性疼痛评估量表在机械通气新生儿急性疼痛评估中都有很好的信度与一致性,其中新生儿急性疼痛评估量表的可行性和临床实用性更好。     

Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model

Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Ca_v3.1 and Ca_v3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain.     

Emerging roles of long non‐coding RNAs in neuropathic pain

Neuropathic pain, a type of chronic and potentially disabling pain resulting from primary injury/dysfunction of the somatosensory nervous system and spinal cord injury, is one of the most intense types of chronic pain, which incurs a significant economic and public health burden. However, our understanding of its cellular and molecular pathogenesis is still far from complete. Long non‐coding RNAs (lncRNAs) are important regulators of gene expression and have recently been characterized as key modulators of neuronal functions. Emerging evidence suggested that lncRNAs are deregulated and play pivotal roles in the development of neuropathic pain. This review summarizes the current knowledge about the roles of deregulated lncRNAs (eg, KCNA2‐AS, uc.48+, NONRATT021972, MRAK009713, XIST, CCAT1) in the development of neuropathic pain. These studies suggested that specific regulation of lncRNAs or their downstream targets might provide novel therapeutic avenues for this refractory disease.     

Heat shock proteins: A dual carrier-adjuvant for an anti-drug vaccine against heroin

Heroin is a highly abused opioid that has reached epidemic status within the United States. Yet, existing therapies to treat addiction are inadequate and frequently result into rates of high recidivism. Vaccination against heroin offers a promising alternative therapeutic option but requires further development to enhance the vaccine’s performance. Hsp70 is a conserved protein with known immunomodulatory properties and is considered an excellent immunodominant antigen. Within an antidrug vaccine context, we envisioned Hsp70 as a potential dual carrier-adjuvant, wherein immunogenicity would be increased by co-localization of adjuvant and antigenic drug hapten. Recombinant Mycobacterium tuberculosis Hsp70 was appended with heroin haptens and the resulting immunoconjugate granted anti-heroin antibody production and blunted heroin-induced antinociception. Moreover, Hsp70 as a carrier protein surpassed our benchmark Her-KLH cocktail through antibody-mediated blockade of 6-acetylmorphine, the main mediator of heroin’s psychoactivity. The work presents a new avenue for exploration in the use of hapten-Hsp70 conjugates to elicit anti-drug immune responses.     

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p?=?0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.