Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle

Neurokinin A (NKA), substance P (SP) and the two peptides combined (SP + NKA) were injected intracutaneously on the forearm and into the temporal muscle of healthy volunteers. Pain intensity, cutaneous wheal and flare responses and tenderness of the temporal muscle were quantitated. SP but not NKA induced cutaneous pain. This relates the algesic effect of SP to the specific N-terminal amino acid sequence of the peptide, not shared by NKA. NKA, however, potentiated the algesic effect of SP as SP + NKA induced a significantly prolonged cutaneous pain sensation. Both peptides induced wheals, but only SP induced flare. These results confirm previous studies relating wheal formation to the identical C-terminal amino acid sequence of the two peptides and flare reaction to the N-terminal part of SP. Injections into the temporal muscle did not cause pain or tenderness.     

Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid signaling in development of neuropathic pain

Lysophosphatidic acid (LPA) is a bioactive lipid that serves as an extracellular signaling molecule acting through cognate G protein-coupled receptors designated LPA(1-6) that mediate a wide range of both normal and pathological effects. Previously, LPA(1), a G(αi)-coupled receptor (which also couples to other G(α) proteins) to reduce cAMP, was shown to be essential for the initiation of neuropathic pain in the partial sciatic nerve ligation (PSNL) mouse model. Subsequent gene expression studies identified LPA(5), a G(α12/13)- and G(q)-coupled receptor that increases cAMP, in a subset of dorsal root ganglion neurons and also within neurons of the spinal cord dorsal horn in a pattern complementing, yet distinct from LPA(1), suggesting its possible involvement in neuropathic pain. We therefore generated an Lpar5 null mutant by targeted deletion followed by PSNL challenge. Homozygous null mutants did not show obvious base-line phenotypic defects. However, following PSNL, LPA(5)-deficient mice were protected from developing neuropathic pain. They also showed reduced phosphorylated cAMP response element-binding protein expression within neurons of the dorsal horn despite continued up-regulation of the characteristic pain-related markers Caα(2)δ(1) and glial fibrillary acidic protein, results that were distinct from those previously observed for LPA(1) deletion. These data expand the influences of LPA signaling in neuropathic pain through a second LPA receptor subtype, LPA(5), involving a mechanistically distinct downstream signaling pathway compared with LPA(1).     

辣椒素及其受体

可以感受痛觉刺激的初级感觉神经元的周围末梢被称为伤害性感受器。这些小直径神经元的末梢可将化学、机械和热刺激信号转化为动作电位,并将这些信息上传到中枢,最后使机体产生痛觉或不舒服的感受。但到目前为止,人们对这些可探测到伤害性刺激的分子所知甚少。1997年成功克隆的辣椒素受体亚型1（vanilloid receptor subtype1,VR1)是近年来科学家们研究的“热点分子”,它是表达于伤害性感受器上的非选择性阳离子通道,已有诸多证据表明其可探测和整合诱发痛觉的化学和热刺激信号,基因敲除小鼠的研究分析也有力证明了该离子通道参与了疼痛及组织损伤后痛觉过敏的产生,而且是热诱发疼痛发生过程的关键分子。     

Impacto del ejercicio físico en variables relacionadas con el bienestar emocional y funcional en adultos mayores

Background and aimThe benefits of the physical exercise in aging, and specially in frailty, have been associated with reduced risk of mortality, chronic disease, and cognitive and functional impairments. Multi-component training, which combines strength, endurance, balance, and gait training, represents the most beneficial kind of physical exercise in older adults.MethodsGiven the effectiveness of the multi-component training, a physical exercise program «Actívate» (based on the methodology Vivifrail), with the focus on «active aging», was conducted in the present study. Forty-nine older adults over 60 years participated in this program.ResultsThe physical exercise intervention led to a reduction in diastolic blood pressure, pain threshold and sleep disturbances (e. g. hypersomnia) (t ≥ 2.72, p < 0.01), as well as an increase of walking speed (t = 7.84, p ≤ 0.001). Further, quality of life factors (GENCAT scale), like emotional well-being, personal development, physical well-being, self-determination, and social inclusion, were greater after intervention (t ≥ ?2.06, p < 0.05).ConclusionsThese findings underline the benefits of multi-component training in functionality of older adults, and further, provide relevant aspects about the modulation of pain perception, sleep disturbances, social factors and physical and emotional well-being. Physical exercise programs such as «Actívate» should be promoted, in order to encourage healthy lifestyle habits, in the older adults’ population.     

腕踝针联合耳穴压豆治疗肝癌癌痛的疗效及对心理状态和血清疼痛介质的影响

摘要 目的：观察腕踝针联合耳穴压豆治疗原发性肝癌（PHC）癌痛的疗效及对心理状态和血清疼痛介质的影响。方法：选取湖南中医药大学第一附属医院2020年3月~2022年12月期间收治的PHC癌痛患者117例,按随机数字表法分为对照组和联合组,例数分别为58例和59例。两组患者均接受常规疼痛处理,对照组患者接受耳穴压豆治疗,联合组在对照组的基础上接受腕踝针治疗。对比两组疼痛缓解率、临床指标、心理状态和疼痛介质水平。结果：联合组的疼痛缓解率高于对照组（P<0.05）。联合组的数字疼痛法（NRS）评分低于对照组,止痛起效时间、每次疼痛持续时间短于对照组,爆发痛次少于对照组（P<0.05）。治疗后,两组焦虑自评量表（SAS）、抑郁自评量表（SDS）评分下降,且联合组低于对照组（P<0.05）。治疗后,两组5-羟色胺（5-HT）、P物质（SP）、前列腺素E₂（PGE₂）下降,且联合组低于对照组（P<0.05）。结论：腕踝针联合耳穴压豆治疗PHC癌痛,可有效减轻疼痛症状,降低血清疼痛介质水平,同时还可有效调节患者的心理状态,应用价值较好。     

不同剂量艾司氯胺酮对腹腔镜全子宫切除术患者术后疼痛和情绪状态的影响

摘要 目的：探讨不同剂量艾司氯胺酮对腹腔镜全子宫切除术患者术后疼痛和情绪状态的影响。方法：按照随机数表法,选择2022年1月至2023年4月我院行腹腔镜全子宫切除术患者120例分为对照组（A组,n=40）、艾司氯胺酮0.25 mg/kg组（B组,n=40）、艾司氯胺酮0.5 mg/kg组（C组,n=40）。比较三组组围术期指标、术后1、4、8、24 h和48 h的疼痛评定数字量表（NRS）评分及术前1天（PRE1）、术后第1天（POD1）、术后第2天（POD2）的焦虑自评量表（SAS）评分、抑郁自评量表（SDS）评分、血流动力学指标及不良反应。结果：B组和C组术后24 h舒芬太尼镇痛药物用量、补救镇痛例数小于A组,A组、B组苏醒时间、拔管时间短于C组（P＜0.05）。B组、C组术后1 h的NRS评分低于A组（P＜0.05）,B组术后4 h、8 h、24 h的NRS评分低于A组,术后4 h、8 h的NRS评分低于C组（P＜0.05）。与组内PRE1相比,三组POD1的SAS、SDS评分均升高（P＜0.05）。B组、C组POD1、POD2的SAS、SDS评分均低于A组,且C组低于B组（P＜0.05）。与组内PRE1相比,A组POD2的SAS、SDS评分升高（P＜0.05）。与组内PRE1相比,B组POD2的SDS与C组POD2的SAS、SDS均降低（P＜0.05）。在T3时刻,B组和C组的平均动脉压（MAP）、心率（HR）低于A组（P＜0.05）。B组和C组术后恶心呕吐发生率低于A组（P＜0.05）;A组和B组术后头晕、苏醒延迟的发生率低于C组（P＜0.05）;三组术后苏醒期躁动和呼吸抑制的差异无统计学意义（P＞0.05）。结论：0.25 mg/kg的艾司氯胺酮对减轻腹腔镜全子宫切除术患者术后疼痛,减少阿片类药物用量,改善负面情绪的临床效果更佳。     

通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎患者血清炎症因子和疼痛介质的影响

摘要 目的：观察通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎（KOA）患者血清炎症因子和疼痛介质的影响。方法：选择2021年6月-2022年12月期间石家庄市人民医院收治的早期KOA患者80例,采用随机数字表法将患者分为对照组（塞来昔布,40例）和观察组（通滞苏润江胶囊联合塞来昔布,40例）。对比两组疗效、疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分、炎症因子和疼痛介质。结果：观察组临床总有效率高于对照组（P<0.05）。两组治疗1个月后VAS、WOMAC评分下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后前列腺素E₂（PGE₂）、P物质（SP）下降,且观察组低于对照组同时间点（P<0.05）。两组不良反应发生率对比未见统计学差异（P>0.05）。结论：塞来昔布和通滞苏润江胶囊联合治疗早期KOA患者,可缓解疼痛,提高临床治疗效果,改善关节功能,同时还可改善血清炎症因子和疼痛介质水平。     

Spatial summation of heat induced pain within and between dermatomes

The aim was to study spatial summation within and between ipsi- and contralateral dermatomes at different painful temperatures. For heat stimulation we used a computer controlled thermofoil based thermode. The thermode area could be varied in five discrete steps from 3.14 to 15.70 cm2. When we applied the stimuli within a dermatome, the mean heat pain threshold decreased significantly from 45.6 to 43.5 C as the area was increased from minimum (3.14 cm2) to maximum (15.70 cm2). When the areas were increased involving different dermatomes (both ipsi- or contralateral), we found similar decreases in pain threshold. Spatial summation was also found within and between dermatomes at supra-threshold temperatures (46, 48, 50 C).The study shows that spatial summation of pain is most likely a mechanism acting across segments and is existing from pain threshold to tolerance.     

Influence of segmental and extra-segmental conditioning stimuli on cortical potentials evoked by painful electrical stimulation

This study evaluated the effects of two different types of segmental/extra-segmental conditioning stimuli (tonic muscle pain and non-painful vibration) on the subjective experience (perceived pain intensity) and on the cortical evoked potentials to standardized test stimuli (cutaneous electrical stimuli). Twelve subjects participated in two separate sessions to investigate the effects of tonic muscle pain or cutaneous vibration on experimental test stimuli. The experimental protocol contained a baseline registration (test stimuli only), a registration with the test stimuli in combination with the conditioning stimuli, followed by a registration with the test stimuli only. In addition, the effects of the conditioning stimuli were examined at two anatomically separated locations (segmental and extra-segmental). Compared with the test stimulus alone, the perceived pain intensity and peak-to-peak amplitudes of the evoked potentials were unchanged in the presence of non-painful conditioning stimuli at either location. In contrast, a significant decrease of the perceived pain intensity and peak-to-peak amplitudes was found in the presence of painful conditioning stimuli at the extra-segmental sites. Moreover, the topographic maps of the 32-channel recordings suggested that the distribution of the scalp evoked potentials was almost symmetrical around the vertex Cz in the baseline registration. The evoked potentials were generally decreased during hypertonic saline infusion at the extra-segmental sites, but the distribution of the topographic maps did not appear to change. Vibration has previously been shown to inhibit pain, but in the present study the perceived intensity of phasic painful electrical stimuli was unchanged. The reduced perceived pain intensity and the smaller peak-to-peak amplitude of the evoked potential in the presence of extra-segmental conditioning pain are in accordance with the concept of diffuse noxious inhibitory control.     

Coarse Architecture of the Transient Receptor Potential Vanilloid 1 (TRPV1) Ion Channel Determined by Fluorescence Resonance Energy Transfer

The transient receptor potential vanilloid 1 ion channel is responsible for the perception of high temperatures and low extracellular pH, and it is also involved in the response to some pungent compounds. Importantly, it is also associated with the perception of pain and noxious stimuli. Here, we attempt to discern the molecular organization and location of the N and C termini of the transient receptor potential vanilloid 1 ion channel by measuring FRET between genetically attached enhanced yellow and cyan fluorescent protein to the N or C terminus of the channel protein, expressed in transfected HEK 293 cells or Xenopus laevis oocytes. The static measurements of the domain organization were mapped into an available cryo-electron microscopy density of the channel with good agreement. These measurements also provide novel insights into the organization of terminal domains and their proximity to the plasma membrane.