A unique representation of heat allodynia in the human brain

Skin inflammation causes innocuous heat to become painful. This condition, called heat allodynia, is a common feature of pathological pain states. Here, we show that heat allodynia is functionally and neuroanatomically distinct from normal heat pain. We subtracted positron emission tomography scans obtained during painful heating of normal skin from scans during equally intense but normally innocuous heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to the frontal lobe during heat allodynia. The results suggest that different central pathways mediate the intensity and certain qualitative aspects of pain. In making this differentiation, the brain recognizes unique physiological features of different painful conditions, thus permitting adaptive responses to different pain states.     

Sensory reinnervation in microsurgical reconstruction of the heel

Six sensory reinnervation techniques were carried out in 10 patients who underwent reconstruction of the weight-bearing surface of the heel by microsurgical free-tissue transfer. The techniques include the use of neurovascular island flaps, neurosensory flaps, sensory nerve grafts to skin flaps, coaptation of the sensory nerve to the motor nerve of the muscle flaps, direct sensory nerve transfer, and sensory nerve graft transfer. In all patients, some sensation developed, characterized by sensation to light touch, to dull objects, to pinprick, to pain, and to tickling. Three patients developed the ability to distinguish sharp from dull objects and the sensation of pain. The remaining seven had the sensation of touch to various mechanical stimuli. In nine patients, the sensation is located in the weight-bearing surface of the reconstructed heel. Five patients bear weight on the reconstructed surface at least 6 hours per day. Three participate actively in sports. Split-thickness skin graft-muscle flaps were more prone to breakdown than skin flaps. Full-thickness skin flaps appear necessary for the production of pain sensation and the more discriminating sensations. Preliminary results suggest a functional benefit after sensory reinnervation.     

Stimulus features relevant to the perception of sharpness and mechanically evoked cutaneous pain

Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception.     

Skin conductance response to the pain of others predicts later costly helping

People show autonomic responses when they empathize with the suffering of another person. However, little is known about how these autonomic changes are related to prosocial behavior. We measured skin conductance responses (SCRs) and affect ratings in participants while either receiving painful stimulation themselves, or observing pain being inflicted on another person. In a later session, they could prevent the infliction of pain in the other by choosing to endure pain themselves. Our results show that the strength of empathy-related vicarious skin conductance responses predicts later costly helping. Moreover, the higher the match between SCR magnitudes during the observation of pain in others and SCR magnitude during self pain, the more likely a person is to engage in costly helping. We conclude that prosocial motivation is fostered by the strength of the vicarious autonomic response as well as its match with first-hand autonomic experience.     

Modeling of nociceptor transduction in skin thermal pain sensation

All biological bodies live in a thermal environment with the human body as no exception, where skin is the interface with protecting function. When the temperature moves out of normal physiological range, skin fails to protect and pain sensation is evocated. Skin thermal pain is one of the most common problems for humans in everyday life as well as in thermal therapeutic treatments. Nocicetors (special receptor for pain) in skin play an important role in this process, converting the energy from external noxious thermal stimulus into electrical energy via nerve impulses. However, the underlying mechanisms of nociceptors are poorly understood and there have been limited efforts to model the transduction process. In this paper, a model of nociceptor transduction in skin thermal pain is developed in order to build direct relationship between stimuli and neural response, which incorporates a skin thermomechanical model for the calculation of temperature, damage and thermal stress at the location of nociceptor and a revised Hodgkin-Huxley form model for frequency modulation. The model qualitatively reproduces measured relationship between spike rate and temperature. With the addition of chemical and mechanical components, the model can reproduce the continuing perception of pain after temperature has returned to normal. The model can also predict differences in nociceptor activity as a function of nociceptor depth in skin tissue.     

生物活性透明质酸治疗激光所致皮肤创口炎症的临床疗效观察

目的:探讨生物活性透明质酸治疗激光所致皮肤创口炎症的临床疗效。方法:选择我院收治的40例激光皮肤除斑患者为研究对象,按就诊顺序将其分为实验组和对照组。实验组20例患者采用生物活性透明质酸涂抹激光治疗后的皮肤伤口,对照组20例患者采用30分冰袋冷敷皮肤激光治疗后的皮肤伤口,观察和比较两组患者伤口第1-7天的的红肿痛的改善情况。结果:(1)疼痛症状的改善情况:实验组第1天的显效率0%,有效20例,总有效率100%;对照组第1天的显效率0%,有效20例,总有效率100%,两组比较无统计学差异(P0.05)。(2)红肿的改善情况:实验组第1天显效20例,总有效率为100%;对照组第1天显效0例,有效20,总有效率为100%,两组总有效率比较无统计学差异(P0.05),但实验组的显效率明高于对照组,差异具有统计学意义(P0.01)。结论:生物活性透明质酸涂抹可以有效控制皮肤伤口炎症引发的红肿痛,且临床效果明显优于冰袋冷敷,方便可行,值得推广。     

VSD负压引流技术结合游离植皮治疗大面积皮肤缺损的 临床疗效研究

目的：研究VSD负压引流技术结合游离植皮治疗大面积皮肤缺损临床疗效。方法：选择2012年4月至2013年10月入我院接受治疗的大面积皮肤缺损患者65例,将其随机分为观察组（35例）与对照组（30例）。观察组患者术前先采用VSD治疗,游离植皮术后继续给予VSD治疗;对照组患者采取打压植皮或传统打包加压治疗。观察和比较两组患者的皮片成活时间、皮片成活率、术后住院治疗时间、换药次数、疼痛评分及家属满意度。结果：观察组患者的皮片成活时间短于对照组、皮片成活率高于对照组、住院时间短于对照组,换药次数少于对照组,两组之间的差异具有统计学意义（P〈0．05）。此外,观察组患者的疼痛视觉模拟评分明显低于对照组,患者家属的满意度评分明显高于对照组,差异具有统计学意义（P〈0．05）。结论：相对于传统的打压植皮或传统打包加压的技术而言,VSD负压引流技术结合游离植皮在治疗大面积皮肤缺损的临床疗效更好,值得在临床上推广使用。     

1．06μm激光致皮肤痛觉效应的研究

目的：研究1．06μm激光所致人手背皮肤的痛觉效应。方法：以输出波长为1．06μm的脉冲Nd：YAG激光照射人手背皮肤,记录每次刺激激光的能量以及受试者的反应。采用加权概率单位算法计算诱发痛觉概率为50％时对应的激光剂量ED50,即为痛觉阈值。改变光斑大小和脉冲宽度,测定三种不同刺激条件下的痛觉阈值,并探索温度对激光所致痛觉效应的影响。结果：当皮肤温度约为30℃,分别使用光斑直径1．20mm、脉冲宽度85μs,光斑直径1．20mm、脉冲宽度20ns和光斑直径2．56mm、脉冲宽度20ns的激光刺激时,痛觉阈值分别为394mJ／mm^2、36．4mJ／mm^2和8．92mJ／mm^2。在第一种刺激条件下,当皮肤温度为25℃时,剂量为383mJ／mm^2的激光诱发痛觉的概率为16．7％;当皮肤温度为39℃时,剂量为361mJ／mm^2的激光诱发痛觉的概率为56．7％。结论：1．06“m激光所致痛觉的阈值随脉冲宽度的减小、光斑面积的增大和皮肤表面温度的增加而减小。     

The relation of warmth and pain thresholds to skin pigmentation.

Thermal sensitivity increases with skin pigmentation. Absolute thresholds for warmth and pricking pain decreased as skin color increased for 13 Caucasian, 3 Mexican, and 4 Negro subjects. These data replicate and extend a previous psychophysical study of pain sensitivity and are compared with spectrophotometric data from excised skin. The results are considered to be potentially significant for the existence of a dermal light sense.     

封闭式负压引流术联合自体游离皮片植皮治疗四肢皮肤软组织感染创面的疗效观察

探究封闭式负压引流术(VSD)联合自体游离皮片植皮治疗四肢皮肤软组织感染创面的疗效及其对疼痛的影响。方法:选择2018年12月-2020年10月北京积水潭医院收治的四肢皮肤软组织感染创面患者90例,按随机数字表法将其分为对照组和观察组,每组45例。对照组采用传统的治疗方法治疗,观察组采用VSD联合自体游离皮片植皮治疗。对比两组治疗结束后的临床疗效,并观察两组治疗前以及治疗后24 h、3 d的疼痛程度,对比两组一般治疗情况及治疗过程中的不良反应。结果:观察组治疗总有效率为93.33%,显著高于对照组的68.89%,差异有统计学意义(P<0.05)。两组患者在治疗后24 h和3 d的数字疼痛量表(NRS)评分低于治疗前,治疗后3 d NRS疼痛评分低于治疗后24 h(均P<0.05),且治疗后24 h和3 d观察组NRS疼痛评分均显著低于对照组(P均<0.05)。观察组患者并发症的发生率为31.11%,明显低于对照组的57.78%,差异有统计学意义(P<0.05)。观察组换药频率显著低于对照组,且疼痛暂缓时间、创面愈合时间、住院时间更短,差异具有统计学意义(P<0.05)。结论:VSD联合自体游离皮片植皮有利于提高治疗四肢皮肤软组织感染创面的临床疗效,缓解患者疼痛症状,并降低并发症发生率。     

Observing neck movements evokes an excitatory response in the sympathetic nervous system associated with fear of movement in patients with chronic neck pain

Abstract

The objective of this study was to evaluate the response of the sympathetic-excitatory nervous system in patients with chronic neck pain compared with a control group of asymptomatic subjects who underwent an intervention of watching activities involving movements in the neck region. Thirty participants were divided into two groups: patients with chronic neck pain (n?=?15) and the control group (n?=?15). The patients’ neck disability, fear of movement and catastrophism were assessed with a self-report. The recorded variables related to the autonomic nervous system were skin conductance and skin temperature. The ANOVA test revealed significant differences in the increase in skin conductance in the chronic neck pain group after observing the activities (both in the photographs and video) at the end of the observation and 5?minutes after the intervention (p?<?.01; d?>?0.80). There were no significant differences in skin temperature. Ultimately, the correlation analysis revealed a moderate positive correlation between kinesiophobia and skin conductance at 30?seconds (r?=?0.53) and at 60?seconds (r?=?0.52) of observing the activities in the video for the chronic neck pain group. Based on the results of the present study, we suggest that observing activities involving neck movements causes an activation of the sympathetic-excitatory nervous system in patients with chronic neck pain. These changes could be related to a fear of movement when faced with visual exposure to neck movements that could be interpreted as ‘harmful’ or ‘dangerous’.     

Detection of kappa and delta opioid receptors in skin--outside the nervous system

Opioid receptors (OR) are widely expressed in the central nervous system (CNS). Opioid antinociception might be initiated by activation of OR outside the CNS, indicating targeting of peripheral OR could be useful in the treatment of chronic pain. This study was designed to detect OR in skin tissues of healthy volunteers at both mRNA and protein levels. Skin samples from 10 healthy individuals were investigated. Total isolated RNAs were reverse transcribed, amplified and quantified by real-time PCR. Tissue and skin fibroblast OR protein was detected by immunohistochemistry, Western blot, and immunofluorescence. All skin tissue samples expressed delta- (DOR) and kappa-OR (KOR) mRNAs. Using immunohistochemistry, DOR and KOR were localized in skin fibroblast-like and mononuclear cells. Skin fibroblasts in culture expressed DOR and KOR mRNA. Using immunofluorescence, both DOR and KOR proteins were expressed predominantly on the cell membrane with minor staining in the cytoplasm. We suggest that enhanced expression of DOR and KOR in skin justifies the exploration of selective novel delta and kappa agonists for local pain treatment.     

Considerations concerning the neurobiological basis of muscle pain

Nociceptors in skeletal muscle can be sensitized by substances that are released from pathologically altered tissue. In the sensitized state, nociceptors can be activated by low-intensity stimulation; this is probably one of the mechanisms producing deep tenderness. Dorsal horn cells processing input from muscle nociceptors often have multiple receptive fields and additional input from other deep tissues or skin. This may be one of the reasons for the diffuse and ill-localized nature of muscle pain. The degree of convergence from deep tissues and skin in neurones with muscle input can be increased by noxious stimulation of deep tissues. This mechanism might explain phenomena such as spread and referral of muscle pain. In the development of chronic muscle pain, vicious circles may be involved which operate locally in the damaged tissue or via spinal reflexes that alter the biochemical environment of the nociceptors in skeletal muscle.     

Sensory recovery in a split skin graft: pinprick or a thermal sensory analyzer?

Sensory return in a split skin graft is an important factor in the protection of this graft from injury. Hence, three tests were compared: (1) the standard pain test using a simple pin, (2) the cold pain test, and (3) the hot pain test. Both the hot and cold pain tests were performed using the thermal sensory analyzer device. Thirteen patients were investigated; all had split skin grafts applied directly onto deep fascia after malignant melanoma excision on the lower limb. The period after grafting ranged from 4 to 15 years, and the mean age was 46.5 years. The normal contralateral side of each patient was used as the control for that patient. The results were collected in simple data tables and were analyzed using paired t tables for small samples with the level of significance set at p < 0.05. The standard pain test demonstrated that the split skin grafts applied on deep fascia did not recover sensation, even 15 years after surgery (p < 0.001). The hot and cold pain tests were both in agreement with the standard pain test at p < 0.001 and p < 0.03, respectively. The standard pain test is usually performed, as described in this study, using a pin, which is cheap and readily available in any plastic surgery and burn clinic. However, the cold and hot pain tests as performed here using the thermal sensory analyzer device are accurate but are costly, cumbersome, and not available in all clinics except for highly specialized units. Hence, the author would like to dispel the myth that the standard pain test is inaccurate. This might be so in testing sensation in "normal" skin but not in testing the recovery of sensation in a skin graft.     

紫草油治疗肛瘘术后的临床研究

目的观察紫草油对肛瘘术后临床疗效改善情况以及血清中TGF-β1、Smad3的含量变化。方法将我院收治的肛瘘术后患者90例采用简单随机法分为紫草油组、凡士林组和肤痔清组各30例,术后第1天至创面愈合,每天分别给予紫草油、凡士林、肤痔清软膏外用,并于术后第1、7、14、21天观察创面疼痛、水肿、出血情况,以及酶联免疫吸附法(ELISA法)检测患者血清中TGF-β1和Smad3含量。结果 3组患者治疗后均能缓解术后水肿、疼痛、出血症状;紫草油组在治疗后第21天与肤痔清组、凡士林组比较,水肿、疼痛、出血的积分差异显著(P0.05)。治疗后第7、14、21天紫草油组与肤痔清组、凡士林组的TGF-β1含量比较,差异具有统计学意义(P0.05);治疗后组内血清Smad3含量均较治疗前明显降低,差异有统计学意义(P0.05),但治疗后第21天紫草油组与肤痔清组、凡士林组的Smad3含量比较,差异无统计学意义(P0.05)。结论紫草油能明显缓解肛瘘术后创面水肿、疼痛、出血情况,且疗效优于肤痔清及凡士林,能有效提高TGF-β1含量及降低血清Smad3含量,促进创面愈合。     

Body Site Variation of Heat Pain Sensitivity

Thirty-two healthy human subjects provided thresholds for the perception of slight and moderate heat pain. Four body sites were tested bilaterally: thenar eminence of the hand, plantar surface of the foot, dorsolateral forearm, and lateral calf. Thresholds for the glabrous skin of the hand and foot were significantly greater than thresholds for the hairy skin of the arm and leg, the average difference being 1.3°c. Laterality was not a statistically significant factor. Thresholds increased progressively over 2–4 weeks of repeated testing, resulting in values averaging 0.6°c higher in the later sessions. The difference between moderate and slight pain thresholds averaged 1.1°c, and was consistent across body sites and with repeated testing.

The threshold values were normally distributed across subjects. Considerable intersubject variability was observed for both slight and moderate pain thresholds, more so on glabrous than on hairy skin sites. In comparison, the distribution of right-left difference values was narrower, demonstrating less intrasubject versus intersubject variability.

The highly significant difference in thresholds between glabrous and hairy skin sites demonstrates the importance of skin type for heat pain sensitivity. In contrast, there was no significant difference in heat pain sensitivity between comparable sites on the upper versus lower extremities, or between left and right sides.     

The opioid component of the effect of the lacrimal glands on wound healing

Naloxone partially inhibited skin wound contraction and completely blocked acceleration of wound healing in rats with stimulated lacrimal glands. Endorphins were detected in lacrimal glands. Alteration of functional activity of the lacrimal glands produces a considerable effect on pain sensitivity and endorphin blood concentration. Opioid peptides have a considerable effect on the functioning of the lacrimal apparatus and are involved in injury-induced reactions, regulating pain sensitivity, structural homeostasis and producing an anti-stress effect.     

Functional characteristics of the skin receptor structures in animals and man

Threshold electrical reactions of single fibers from the ischiadic nerve of rats to mechanical stimulation and rectangle impulses of focused ultrasound have been compared with respect to the parameters of stimulation to the effect of focused ultrasound on the skin of human fingers evoking different sensations. It was concluded that low-threshold fibers may be associated with tactile reception, mean-threshold ones--with tactile and thermal, whereas high-threshold fibers may be referred to reception of specific skin pain.     

Evaluation of the effects of various chemicals on discharge of and pain caused by jellyfish nematocysts

Jellyfish tentacles in contact with human skin can produce pain swelling and redness. The pain is due to discharge of jellyfish nematocysts and associated toxins and discharge can be caused by a variety of mechanical and chemical stimuli. A series of tests were carried out with chemicals traditionally used to treat jellyfish stings e.g. acetic acid ammonia meat tenderizer baking soda and urea to determine if these chemicals stimulated or inhibited nematocyst discharge and if they brought relief to testers who were exposed to jellyfish tentacles. Chrysaora quinquecirrha (sea nettle) Chiropsalmus quadrumanus (sea wasp) and Physalia physalis (Portuguese man-of-war) were used in the study. It was found that many of the chemicals traditionally used to treat jellyfish stings stimulated nematocyst discharge and did not relieve the pain. However there was immediate relief when a common anesthetic lidocaine was sprayed on the skin of testers in contact with jellyfish tentacles. Initial exposure of tentacle suspensions to lidocaine prevented the nematocyst discharge by subsequent exposure to acetic acid ethanol ammonia or bromelain. Thus lidocaine in addition to acting as an anesthetic on skin in contact with jellyfish tentacles inhibited nematocyst discharge possibly by blocking sodium and/or calcium channels of the nematocytes.