Biomechanics of musculoskeletal pain: dynamics of the neuromatrix.

Pain, due to mechanical stimuli, is a normal, indeed healthy, response of animals to potential or actual damage to tissues. Mammals in general, and humans in particular, have evolved a highly sophisticated system of pain perception, which is characterized in humans by complementary but distinct neural processing of the intensity and location of a noxious stimulus, and a motivational/emotional or affective response to the stimulus. The peripheral and central neurons that comprise this system, which has been called the 'neuromatrix', dynamically (temporally) respond and adapt to noxious biomechanical stimuli. However, phenotypic variability of the neuromatrix can be large, which can result in a host of musculoskeletal conditions that are characterized by altered pain perception, which can and often does alter the course of the condition. This neural plasticity has been well recognized in the central nervous system, but it has only more recently become known that peripheral nociceptors also adapt to their altered extracellular matrix environment. This work reviews the biomechanics of pain focusing on the relevant stimulus that initiates responses by nociceptors to the cognitive perception of pain.     

Locating the beginnings of pain

This paper examines the question of whether a fetus can feel pain. The question is divided into four sub questions: What is pain? What is the neurology of pain processing? What is the fetus? Are there good reasons for holding that fetuses feel pain? Pain is suggested to be a multi-dimensional phenomenon drawing on emotional and sensory processes – a consequence of a gradual development involving a number of noxious events rather than an automatic consequence of injury or disease. The non-automaticity of pain is emphasised in the discussion of pain neurology that defies explanations based on a specialised neuronal ‘pain-centre’. The development of the fetus is considered with respect to developmental neurobiology, behavioural and neurological responses to stimulation, and hormonal and neurochemical responses to noxious stimulation. While acknowledging that the development of the fetus is complex, especially after 26 weeks gestation, considerable development is still to occur, even after birth. The fetal pain literature is criticised for tending to exaggerate fetal development. Finally, the difficulty of explaining the subjectivity of pain in materialist terms is discussed. Pain is suggested to arise with development of the necessary neurological, cognitive and emotional structures. Pain experience is placed at approximately 12 months of age, though this is within the context of a continuum of awareness rather than a straight ‘on-off’ switch. The major moral implication of this stance is to place the burden of proof for analgesic use onto clinical measures, rather than relying upon the, so far, poorly supported assumption of pain awareness.     

杏仁核参与疼痛情绪过程的研究进展

本文综述了近年来关于杏仁核参与疼痛过程的研究进展。疼痛伴随有强烈的情绪反应,而杏仁核是情绪调控中的一个关键核团。最近,越来越多的证据支持杏仁核参与痛觉的编码和调制过程。杏仁核对来自脊髓和三叉神经核的伤害性信息及皮层和丘脑的多种感觉信息进行整合,产生负性情绪,并对疼痛刺激作出相应的行为反应。同时,杏仁核也通过与导水管周围灰质、延髓头端腹内侧区及其它脑干核团的纤维联系参与镇痛过程。     

Electrophysiological Measurements and Analysis of Nociception in Human Infants

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns.The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord.This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.     

Effect of neurogenic acupoint cupping on high sensitive C-reactive protein and pain perception in female chronic pelvic pain: A randomized controlled trial

Objectives:To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint.Methods:Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ).Results:Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ “Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)” and PPIQ (p<0.05).Conclusion:Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP.     

大鼠杏仁核簇与痛觉调制的关系

目的：研究伤害性刺激对大鼠杏仁核簇中各亚核痛反应神经元电活动的影响。方法：用串电脉冲刺激坐骨神经作为伤害性刺激,用玻璃微电极引导神经元放电。结果：杏仁核簇中多个亚核均存在痛反应神经元。伤害性刺激使痛兴奋神经元(PEN)诱发放电频率增加;使痛抑制神经元(PIN)诱发放电频率降低,并出现放电频率极低现象;两类神经元电活动相互配合。腹腔注射吗啡(10mg／kg)可以对抗伤害性刺激对痛反应神经元的作用。结论：杏仁核簇中的部分亚核在感受、整合和传递痛觉信息方面起一定作用,是中枢神经系统控制和处理痛觉信息的一个组成部分。     

Mechanisms of ATP release in pain: role of pannexin and connexin channels

Pain is a physiological response to bodily damage and serves as a warning of potential threat. Pain can also transform from an acute response to noxious stimuli to a chronic condition with notable emotional and psychological components that requires treatment. Indeed, the management of chronic pain is currently an important unmet societal need. Several reports have implicated the release of the neurotransmitter adenosine triphosphate (ATP) and subsequent activation of purinergic receptors in distinct pain etiologies. Purinergic receptors are broadly expressed in peripheral neurons and the spinal cord; thus, purinergic signaling in sensory neurons or in spinal circuits may be critical for pain processing. Nevertheless, an outstanding question remains: what are the mechanisms of ATP release that initiate nociceptive signaling? Connexin and pannexin channels are established conduits of ATP release and have been suggested to play important roles in a variety of pathologies, including several models of pain. As such, these large-pore channels represent a new and exciting putative pharmacological target for pain treatment. Herein, we will review the current evidence for a role of connexin and pannexin channels in ATP release during nociceptive signaling, such as neuropathic and inflammatory pain. Collectively, these studies provide compelling evidence for an important role of connexins and pannexins in pain processing.     

Changes in pain perception and hormones pre- and post-kumdo competition

The psychological stress of competition is a powerful stimulus affecting numerous hormones, which in turn change how pain is perceived. This study investigated whether a kumdo (kendo) team competition may be related to changes in hormones and pain. Seventeen healthy male kumdo practitioners participated in this experiment. Pain experiments were conducted by applying noxious stimuli with a thermal stimulator 10 min before a kumdo competition and 30 min post-competition. Serum testosterone, cortisol, beta-endorphin levels, pain thresholds, pain ratings at 48 °C and during blood sampling (sampling pain), anxiety, blood pressure, and heart rate were measured pre- and post-competition. Anxiety, pain threshold, testosterone/cortisol ratio, and blood pressure were significantly higher pre-competition compared to post-competition, while cortisol and pain ratings were significantly lower pre-competition than post-competition. There were significant correlations between the number of previous competitions and testosterone levels both pre-competition and post-competition. In pre-competition measurements, sampling pain increased with an increase in systolic blood pressure, heart rate, and beta-endorphins, and a decrease in age. In post-competition measurements, sampling pain increased with an increase in diastolic blood pressure and a decrease in testosterone levels. These results indicate that severe psychological pre-competition stress was associated with reduced pain ratings, perhaps in order to improve athletic performance. This also suggests that competitors may be at risk of potential injury due to changes in pain perception, and careful consideration should be taken to avoid potential injury before and during competition.     

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.     

痛觉诱发电位的研究进展

痛觉诱发电位的研究在过去的几十年内取得了重要进展 ,出现了许多用于被试的诱发明确疼痛感的刺激技术 ,并与诱发电位方法学联合应用 ,已经成为脑映像学研究中重要的组成部分。本文从刺激技术、痛觉诱发电位成分分析和偶极子源分析等方面出发 ,讨论了痛觉诱发电位的研究进展     

椎体成形术治疗脊柱压缩骨折的临床疗效

目的:探讨脊柱压缩骨折患者的椎体成形术应用方法与效果。方法:脊柱压缩骨折患者150例根据随机抽签法分为治疗组与对照组各75例,对照组给予传统开放性手术,治疗组给予椎体成形术。通过比较两组手术时间,术中出血量,术后住院时间,术后疼痛评分,术后局部Cobb角的差异评价治疗效果,其中,疼痛评分采用VAS量表,局部Cobb角通过脊椎侧围X片测定。结果:所有患者都顺利完成手术,无严重并发症发生,治疗组的术中出血量与术后住院时间明显少于对照组(P0.05)。两组术前疼痛评分对比差异无统计学意义,术后疼痛评分都呈现明显下降的趋势(P0.05),同时术后治疗组的疼痛评分明显低于对照组(P0.05)。两组术前局部Cobb角对比差异无统计学意义,术后局部Cobb角都明显下降(P0.05),同时术后治疗组的局部Cobb角都明显低于对照组(P0.05)。结论:脊柱压缩骨折患者的椎体成形术应用能有效缓解疼痛程度,改善椎体前中部高度脊柱后凸情况,对于患者的创伤比较少,有很好的推广应用价值。     

康复训练联合超激光对全膝关节置换术患者术后疼痛、膝关节功能和生活质量的影响

目的:探讨康复训练联合超激光对全膝关节置换术(TKA)患者术后疼痛、膝关节功能和生活质量的影响。方法:选取2016年1月-2017年9月期间在青海省人民医院疼痛科行TKA术式的患者73例为研究对象。根据随机数字表法将患者分为对照组(n=36)和研究组(n=37),对照组患者术后给予康复训练,研究组在对照组基础上联合超激光进行治疗,两组均治疗6周。比较治疗前、治疗6周后(治疗后)两组患者膝关节功能状况、疼痛程度、膝关节屈曲度和伸展度,同时随访3个月,观察两组患者生活质量情况。结果:两组患者治疗后视觉模拟疼痛量表(VAS)评分均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后膝关节伸展度、屈曲度、美国特种外科医院(HSS)评分均较治疗前升高,且研究组高于对照组(P0.05)。随访3个月,两组患者的生理功能(PF)、生理职能(RF)、躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、情感职能(RE)以及心理健康(MH)等评分较治疗前均升高,且研究组高于对照组(P0.05)。结论:TKA患者给予康复训练联合超激光治疗效果较好,可显著改善患者膝关节功能,减轻患者疼痛,提高患者生活质量。     

Effect of chronic intermittent exposure to AM radiofrequency field on responses to various types of noxious stimuli in growing rats

There are several reports of altered pain sensation after exposure (from a few minutes to hours in single or repeated doses for 2-3 weeks) to electromagnetic fields (EMF) in adults. The commonly utilized noxious stimulus is radiant heat. The nociceptive responses are known to be influenced by characteristics of stimulus, organism, and environment. We studied the pattern of nociceptive responses to various noxious stimuli in growing rats exposed to radiofrequency field (73.5 MHz amplitude modulated, 16 Hz power density 1.33 mw/cm(2), SAR = 0.4 w/kg) for 45 d (2 h/d). Threshold current for stimulation of nociceptive afferents to mediate motor response of tail (TF), vocalization during stimulus (VD), and vocalization after discharge (VA); the withdrawal latency of tail (TFL) and hind paw (HPL) to thermal noxious stimulus and tonic pain responses were recorded in every rat. The TFL was not affected, HPL was decreased (p < 0.01), and the thresholds of TF and VD were not affected, while, that of VA was significantly decreased. The tonic pain rating was decreased (p < 0.01). A decrease in the threshold of VA (p < 0.01) is indicative of an increase in the emotional component of the response to the phasic pain, whereas a decrease in the pain rating indicates analgesia in response to the tonic pain. The results of our study suggest that chronic (45 d), intermittent (2 h/d) amplitude modulated RF field exposure to the peripubertal rat increases the emotional component of phasic pain over a basal eaualgesic state, while late response to tonic pain is decreased. The data suggest that amplitude modulated RF field differentially affects the mechanisms involved in the processing of various noxious stimuli.     

Pain additivity,diffuse noxious inhibitory controls,and attention: A functional measurement analysis

This study utilized the methodology of Functional Measurement theory to investigate the additivity of painful and non-painful thermally induced experiences at one body site with those produced by brief noxious and innocuous electrical stimuli at another. Forty healthy young subjects were tested, using a Peltier thermode to induce tonic pain and an electrocutaneous stimulator for presenting phasic pain, under conditions of either full attention or visual/cognitive distraction (counting numerous light signals) in order to evaluate whether the summed effects are attributable to refocused attention. Six levels of intensity were combined in a factorial design for both tonic and phasic pain. Subjects indicated the overall strength of their dual perception on a visual analog scale. Stimuli showed complex patterns of interaction. Two stimuli were generally rated as greater than one, but the summation was far from additive and greatly influenced by the intensity of the stronger stimulus, suggesting inhibitory action. In general, tonic heat pain strongly affected the perception of phasic electrocutaneous pain whereas the reverse was only partly true. Distraction had a very small effect, suggesting that the “pain inhibits pain” phenomenon attributable to diffuse noxious inhibitory controls (DNIC) is not due to attentional processes. Our data also relate to issues regarding spatial summation across dermatomes and to adaptation level effects in pain, in which a strong painful experience serves as an anchor or comparison point by which others are judged. The psychophysical findings provide a perceptual foundation for clinical phenomena in which patients face with comorbid pain disorders.     

Assessment metrics for littoral seagrass under the European Water Framework Directive; outcomes of UK intercalibration with the Netherlands

Under the Water Framework Directive (WFD) taxonomic composition, presence of disturbance sensitive species, abundance and cover are stated attributes for monitoring the status of marine angiosperms; a biological quality element required for assessment of environmental condition. Member States (MS) are required to devise metrics for assessing these attributes to establish ecological status of water bodies. Furthermore the Directive requires intercalibration of metrics and data between MSs. Seagrass are the only truly marine angiosperms. The proposed suites of UK and Dutch metrics for assessing the specified seagrass attributes are described and comparisons made. UK and Dutch metrics are intercalibrated through testing against each nationality’s seagrass data. Strong agreement is established in the outcomes of the two suites of tools; >83%. Differences in outcomes are usually due to lack of availability of raw data. Importantly, where outcomes differ they still fall on the same side of the Good/Moderate boundary. Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users Handling editor: K. Martens An erratum to this article is available at .     

Pain and Pessimism: Dairy Calves Exhibit Negative Judgement Bias following Hot-Iron Disbudding

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, but emotional states are difficult to directly assess in animals. Researchers have assessed pain using behavioural and physiological measures, but these approaches are limited to understanding the arousal rather than valence of the emotional experience. Cognitive bias tasks show that depressed humans judge ambiguous events negatively and this technique has been applied to assess emotional states in animals. However, limited research has examined how pain states affect cognitive processes in animals. Here we present the first evidence of cognitive bias in response to pain in any non-human species. In two experiments, dairy calves (n = 17) were trained to respond differentially to red and white video screens and then tested with unreinforced ambiguous colours in two or three test sessions before and two sessions after the routine practice of hot-iron disbudding. After disbudding calves were more likely to judge ambiguous colours as negative. This ‘pessimistic’ bias indicates that post-operative pain following hot-iron disbudding results in a negative change in emotional state.     

Role of neurogenic inflammation in pancreatitis and pancreatic pain

Pain arising from pancreatic diseases can become chronic and difficult to treat. There is a paucity of knowledge regarding the mechanisms that sensitize neural pathways that transmit noxious information from visceral organs. In this review, neurogenic inflammation is presented as a possible amplifier of the noxious signal from peripheral organs including the pancreas. The nerve pathways that transmit pancreatic pain are also reviewed as a conduit of the amplified signals. It is likely that components of these visceral pain pathways can also be sensitized after neurogenic inflammation.     

Predictability of Painful Stimulation Modulates the Somatosensory-Evoked Potential in the Rat

Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the effect of predictability on the SEP in animals, classical fear conditioning was applied to compare SEPs between rats receiving SEP-evoking electrical stimuli either predictably or unpredictably. As in humans, the rat’s SEP increased when SEP-evoking stimuli were administered unpredictably. These data support the hypothesis that the predictability of noxious stimuli plays a distinctive role in the processing of these stimuli in animals. The influence of predictability should be considered when studying nociception and pain in animals. Additionally, this finding suggests that animals confronted with (un)predictable noxious stimuli can be used to investigate the mechanisms underlying the influence of predictability on central processing of noxious stimuli.     

原发性三叉神经痛和疱疹后三叉神经痛临床特征及射频热凝术后效果分析

摘要 目的：探讨原发性三叉神经痛（PTN）和疱疹后三叉神经痛（PHN）的临床特征,并比较经卵圆孔射频热凝术（RF-TC）治疗PTN和PHN的临床疗效。方法：随机选取2019年1月至2020年8月在我院治疗的三叉神经痛患者123例,其中原发性三叉神经痛90例,带状疱疹后神经痛33例。所有患者均通过RF-TC进行治疗,治疗后通过视觉模拟量表（VAS）、巴罗神经研究所疼痛强度量表对面部疼痛评分进行疼痛评估,通过巴罗神经研究所麻木评分进行麻木评定,通过健康问卷-9对患者抑郁情况进行评估,通过匹斯堡睡眠质量指数测量患者心理状态。结果：PTN患者发病年龄显著低于PHN患者（P<0.05）,而病程显著高于PHN患者（P<0.05）;PHN患者的眼支发生率高于PTN患者（39.39% vs 8.89%, P<0.05）。两组患者经RF-TC治疗前后VAS评分无显著差异（P>0.05）。PHN组从轻度到重度影响睡眠质量的比例显著高于PTN组（30.30% vs 10.00%, P<0.05）。PTN组患者治疗后中重度抑郁患者比例显著高于PHN组患者（21.11% vs 9.09%, P<0.05）。两组患者经RF-TC治疗后,临床治疗有效率、面麻木程度以及巴罗神经研究所疼痛强度量表评定的面部疼痛无显著差异（P>0.05）。结论：经卵圆孔射频热凝术治疗原发性三叉神经痛和带状疱疹后三叉神经痛是安全有效的,但治疗后疱疹后三叉神经痛失眠的发生率较高,而原发性三叉神经痛的抑郁发生率较高。