Pain—Mechanisms and Management

In the past two decades there has been remarkable progress in understanding the neural mechanisms of pain. However, chronic pain is poorly understood and, by definition, poorly managed. In addition to hyperactivity of the sympathetic nervous system and damage to normal inhibitory mechanisms, social and psychological factors play a major role in producing the disability of chronic pain. New approaches to manage chronic pain include nonopiate drugs, transcutaneous electral nerve stimulation and psychological and behavioral methods. A nervous system network has recently been described that suppresses pain. This analgesic action is mediated by endogenous opioid peptides (endorphins) and by biogenic amines. The analgesia network can be activated either by electral stimulation or by opiates such as morphine or methadone.     

经皮穴位电刺激治疗术后疼痛的研究进展

术后疼痛是术后常见的一种伤害性疼痛,随着舒适化医疗的倡导,经皮穴位电刺激因其无创、安全等优点受到关注。经皮穴位电刺激是将经皮神经电刺激与针灸穴位理论相结合的一种方法,虽有研究证实其频率、波形、强度、刺激时间的设定及不同穴位的配伍对镇痛效果均可产生较大的影响,但在规范化方面仍有不足。本文总结其使用方法及镇痛疗效,以期对经皮穴位电刺激应用于临床提供最优参数及穴位配伍,使之规范化,从而发挥出最佳镇痛效果。     

Electrical stimulation of peripheral and central pathways for the relief of musculoskeletal pain

One method for the treatment of chronic musculoskeletal pain involves stimulation of the peripheral or central nervous system. Such stimulation includes transcutaneous electrical nerve stimulation, dorsal column stimulation, and deep brain stimulation. This review discusses the clinical use of electrical stimulation for the relief of musculoskeletal pain, and describes the results of studies conducted in our laboratory suggesting that such stimulation reduces pain transmission along sensory-discriminative pathways.     

Percutaneous central gray stimulation for cancer pain.

Electrical stimulation of the periventricular and periaqueductal gray matter via a percutaneous electrode appears to be a useful method for relieving cancer pain with midline and bilateral distribution. Due to the nondestructive character and the minor surgical risks involved in this procedure it may be tried before considering bilateral cordotomy or myelotomy. A possible mechanism of action or at least a contributive factor to the pain relief is the activation of endorphins.     

Ischemic heart disease without anginal pain]

Prolonged ECG-recording with Holter's technique facilitated detection of heart ischemic episodes without accompanying anginal pain. It is estimated that ischemic heart disease without anginal pain involves about 20% of all patients with IHD, and the episodes of heart ischemia with and without anginal pain occur in 30% of these patients. A course of ischemic heart disease without anginal pain may be due to decreased sensitivity to pain stimuli caused by the lesions to sensory afferent nerves or by the increased serum endorphins. The majority of experiments has shown that asymptomatic ischemic heart disease increases the risk of sudden death. It may be explained by increased physical exercise attempted by these patients and not compliance with anti-sclerotic therapeutical and preventive measures. The treatment of asymptomatic ischemic heart disease is similar to that in symptomatic froms of this diseases.     

Electrical stimulation in multiple sclerosis. Comparison of transcutaneous electrical stimulation and epidural spinal cord stimulation

Forty-nine multiple sclerosis patients with bladder symptoms and/or walking disability were subjected to a therapeutic trial with electrical spinal cord stimulation and transcutaneous electrical stimulation, a second aim being to compare these two treatments. A clear subjective improvement in bladder symptoms was achieved in the majority of the cases, and this was substantiated by objective parameters. In a proportion of cases a more moderate improvement seems to have been achieved in a variety of symptoms. Transcutaneous electrical stimulation seems to be a useful selection procedure for later electrical spinal cord stimulation.     

Response of external inspiration to the movements induced by transcutaneous spinal cord stimulation

The dynamic of the parameters of lung ventilation and gas exchange have been studied in 10 young male subjects during involuntary stepping movements induced by transcutaneous spinal cord electrical stimulation applied in the projection of T ₁₁–T ₁₂ vertebrae and during voluntary stepping movements. It has been found that the transcutaneous spinal cord stimulation inducing stepping movements leads to an increase in breathing frequency and a reduction in tidal volume. These effects may be mediated by some neurogenic factors associated with muscular activity during stepping movements, the activation of abdominal expiratory muscles, and the interaction between the stepping pattern and breathing generators.     

Study by auditory evoked potentials of the efficacy of transcutaneous electric stimulation in the treatment of tinnitus

Thirty patients complaining about tinnitus were treated by transcutaneous tragal electrical stimulation. The effect of this treatment has been evaluated by BASR recordings before and after treatment. Taking into account the subjective results three groups are described. The first one (10 patients) is relieved of tinnitus. In second and third group the symptoms still exist, whatever the electrode's position (anode or cathode in tragal position). When BASR are studied before the electrical stimulation no inter-subjects difference can be found. After stimulation, the left delta I-V latency is significatively lengthened, and the wave I latency is shortened in the first group. The study of the two other groups do not reveal any difference between the pre- and the post- stimulation evaluation. So the BASR appears to be a good predictive tool for tinnitus suppression by electrical stimulation.     

反复电针对慢性痛的累加治疗作用及其机制研究

本研究从基础和临床两方面观察了反复电针对慢性痛的累加治疗作用,并结合疼痛患者及慢性痛动物模型中几种神经肽的放射免疫测定及相应受体拮抗剂的药理学研究结果,探讨了产生累加效应的可能机制。结果表明,在临床脊髓损伤性痉挛患者,１００Ｈｚ穴位体表电刺激有效地缓解痉挛并有累加效应;在临床慢性痛患者,２／１５Ｈｚ变频ＴＥＮＳ刺激有效地治疗疼痛并具有累加效应。在关节炎模型大鼠,电针刺激能产生明显的镇痛并具有累加效     

A brainstem "mini-discharge" syndrome (anesthesia dolorosa)

Chronic pain consisting of anesthesia dolorosa secondary to bilateral interruption of the trigeminal nerves is presented as a brain stem reticular denervation syndrome. Electrothalamograms revealed fast frequency discharges in the mesothalamic prerubral and centermedian reticular formation. Mesothalamic electrical stimulation attenuated the discharges. Pain and other symptoms presumably of brainstem origin also were attenuated or abolished by therapeutic electrical stimulation twice daily. It is postulated that brain stem-represented behavioral generators are implicated by the reticular discharges in order to produce the complex symptomatology. Consequently the symptom complex is collectively identified as a brainstem "mini-discharge" syndrome. A theoretical discussion is presented to defend the thesis that reticular denervation-induced low threshold discharge system accounts for the episodic states of pain, dyskinesia, mood, and memory disturbances.     

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     

不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响

目的:评价不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响。方法:共选取择期行妇科腹腔镜手术患者80例,根据经皮穴位电刺激频率不同随机分成4组,N组患者20人不做经皮穴位电刺激,E1-E3组患者60人术中在内关、百会和风池穴使用经皮穴位电刺激,其中E1组经皮穴位电刺激频率为2Hz,E2组频率为100 Hz,E3组频率为2/100 Hz。观察四组患者术后认知功能障碍发生率之间的差异。结果:与N组比较E1-E3组POCD的发生率明显较低,差异具有统计学意义(P0.05)。但E1、E2、E3组患者POCD的发生率比较无明显差异(P0.05)。结论:经皮穴位电刺激内关、百会和风池穴可有效降低妇科腹腔镜手术患者术后认知功能障碍的发生率,但不同频率参数的刺激效果无明显差异。     

Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus

11 patients with chronic intractable pain of at least 3 years' duration underwent a morphine infusion test, the results of which suggested a syndrome of superimposed somatogenic and neurogenic pain components. They then underwent stereotactic implantation of a dual-channel brain stimulation system with two brain electrodes, one in the left periaqueductal gray matter (PAG) and the other in the sensory thalamus contralateral to the neurogenic pain. Using this system, all patients have obtained excellent simultaneous relief of both pain components (follow-up 12-36 months). The findings support a notion of two separate sensory modulating systems. They indicate that combined electrical stimulation of the PAG and sensory thalamus is a technically feasible and clinically satisfactory modality for the control of pain in humans, and they appear to indicate that better pain control is obtained by continuous, cycled stimulation of the PAG than by the conventional mode of stimulation.     

Relief of dental pain by ice massage of the hand.

Patients suffering from acute dental pain were treated with ice massage of the web between the thumb and index finger of the hand on the same side as the painful region. Control groups received tactile massage alone or with explicit suggestion that the massage was intended to alleviate their pain. Changes in pain intensity produced by the procedures were measured with the McGill Pain Questionnaire. Ice massage decreased the intensity of the dental pain by 50% or more in the majority of patients. Furthermore, the pain reductions produced by ice massage were significantly larger than those produced by tactile massage alone or with explicit suggestion. The results indicate that ice massage has pain-reducing effects comparable to those of transcutaneous electrical stimulation and acupuncture. The fact that cold signals are transmitted to the spinal cord exclusively by A-delta fibres and not by C fibres provides a potential method for differentiating the various feedback systems that mediate analgesia produced by different forms of intense sensory input. Ice massage provides a simple method for the palliative control of pain in dental clinics.     

TNS-evoked long loop effects.

Local analgesia can be produced by transcutaneous electrical stimulation of peripheral nerves. This is used in the treatment of chronic pain states. Its clinical effectiveness depends on two points; namely (1) the stimulation has to be perceptible, and (2) paresthesias elicited by TNS must be localized in the area of pain. To verify this in healthy subjects we produced an experimental pain by radiant heating of the skin and tested the analgesic effect of TNS. TNS stimuli parameters (duration, amplitude and frequency) were determined so that double blind conditions were given. Stimulation with small rectangular pulses showed the best analgesic effect especially at a stimulation rate of 100 Hz. The stimulation of various nerves showed that most of the analgesic effects depend on spinal level mechanisms but probably long loop effects are involved.     

Electrical stimulation of the trigeminal tract in chronic, intractable facial neuralgia

In this paper the treatment of patients with chronic, intractable trigeminal neuralgia by invasive electrical stimulation of the Gasserion ganglion is reviewed. Two different surgical techniques are employed in this treatment. Most frequently, a method similar to the traditional technique for percutaneous glycerol and radiofrequency trigeminal rhizolysis is used: a small percutaneous stimulation electrode is advanced under fluoroscopic control through a thin needle via the foramen ovale to the Gasserian cistern. Some neurosurgeons use an open surgical technique by which the Gasserian ganglion is approached subtemporally and extradurally, and the bipolar pad electrode is sutured to the dura. When percutaneous test stimulation is successful (at least 50% pain relief) the electrode is internalized and connected to a subcutaneous pulse generator or RF-receiver. Data from 8 clinical studies, including 267 patients have been reviewed. Of all 233 patients with medication-resistant atypical trigeminal neuralgia 48% had at least 50% long term pain relief. The result of test stimulation is a good predictor of the long term effect, because 83% of all patients with successful test stimulation had at least 50% long term relief, and 70% had at least 75% long term relief. Patients generally preferred this invasive method over TENS. The success rate in patients with postherpetic trigeminal neuralgia was very low (less than 10%). It is suggested that the likelihood of pain relief by electrical stimulation is inversely related to the degree of sensory loss. It is concluded that invasive stimulation of the Gasserian ganglion is a promising treatment modality for patients with chronic, intractable, atypical trigeminal neuralgia.     

A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI]

BACKGROUND: Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-controlled) transcutaneous VNS (tVNS) at the inner side of the tragus. This paper shows the feasibility of these and their potential for brainstem and cerebral activations as measured by blood oxygenation level dependent functional MRI (BOLD fMRI). MATERIALS AND METHODS: In total, four healthy male adults were scanned inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. We ensured that our newly developed tVNS stimulator was adapted to be an MR-safe stimulation device. In the experiment, cortical and brainstem representations during tVNS were compared to a baseline. RESULTS: A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left locus coeruleus, the thalamus (left > right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula. Deactivations were found in the right nucleus accumbens and the right cerebellar hemisphere. CONCLUSION: The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP are discussed and new possibilities of tVNS are hypothesised.     

Effect of transcutaneous transcerebral electrostimulation as electroanesthesia on the beta-endorphin content of the cerebrospinal fluid and blood plasma

The beta-endorphin content was measured in the cerebrospinal fluid (CSF) and blood plasma of patients before and after 30 minutes of transcutaneous transcerebral electric stimulation in the electric anesthesia mode. The output current was biphasic and rectangular. It was composed of high-frequency pulse trains (peak-to-peak intensity 250-300 mA, frequency 167 kHz) modulated by low frequency (77 Hz). Electrical stimulation resulted in an appreciable increase in the beta-endorphin content in the CSF and blood plasma of patients. The data obtained attest to the intensification of the neuromodulator release to the CSF and blood plasma and to the involvement of the endorphinergic brain systems in the realization of the analgetic effect of transcutaneous transcerebral electric stimulation.     

Pain relief following stimulation of the pontomesencephalic parabrachial region in humans: brain sites for nonopiate-mediated pain control

It has been demonstrated that stimulation of the pontomesencephalic parabrachial region (PBR) by microinjection of cholinergic drugs or electricity in the cat produces potent pain suppression which is not antagonized by the opiate antagonist, naloxone. We report the application of electrical PBR stimulation in 2 patients whose pain was resistant to conventional methods of treatment including morphine administration. Intermittent use of low-frequency PBR stimulation was found to relieve pain in these patients. The present results appear to suggest that PBR stimulation, unlike periaqueductal gray stimulation, may be useful for the control of morphine-resistant pain in humans.     

经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中的应用效果分析

摘要 目的：探讨经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中的应用效果。方法：选取我院2019年1月到2022年12月收治的120例采取膝关节前交叉韧带损伤重建术的患者作为研究对象,分为观察组与对照组,每组60例。对照组采取常规术后康复治疗,观察组采取经皮穴位电刺激联合下肢康复机器人康复治疗,对比两组患者康复治疗效果,位置觉和运动觉,疼痛情况与肿胀情况,膝关节功能以及生活质量。结果：观察组治疗总有效率高于对照组（P＜0.05）;治疗前两组患者患肢肿胀值、视觉模拟量表（VAS）评分对比无差异（P＞0.05）,治疗后均降低,且观察组较对照组低（P＜0.05）;两组患者的治疗前膝关节75度、45度、15度位置觉,伸膝、屈膝运动觉对比无差异（P>0.05）,治疗后两组患者膝关节75度、45度、15度位置觉,伸膝、屈膝运动觉均下降,且观察组较对照组低（P＜0.05）;治疗前两组患者膝关节主观（IKDC）评分、膝关节功能（Lysholm）评分对比无差异（P＞0.05）,治疗后均降低,且观察组较对照组低（P＜0.05）;两组患者治疗前生活质量相关评分对比无差异（P＜0.05）,治疗后均升高,且观察组较对照组高（P＜0.05）。结论：经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中应用效果显著,能够改善患者膝关节位置觉和运动觉,减轻远期疼痛情况与肿胀情况,提升膝关节功能,患者生活质量较好。