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     

What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain?

Research suggests that fibromyalgia is a central, widespread pain syndrome supported by a generalized disturbance in central nervous system pain processing. Over the past decades, multiple lines of research have identified the locus for many functional, chronic pain disorders to the central nervous system, and the brain. In recent years, brain neuroimaging techniques have heralded a revolution in our understanding of chronic pain, as they have allowed researchers to non-invasively (or minimally invasively) evaluate human patients suffering from various pain disorders. While many neuroimaging techniques have been developed, growing interest in two specific imaging modalities has led to significant contributions to chronic pain research. For instance, resting functional connectivity magnetic resonance imaging (fcMRI) is a recent adaptation of fMRI that examines intrinsic brain connectivity - defined as synchronous oscillations of the fMRI signal that occurs in the resting basal state. Proton magnetic resonance spectroscopy (¹H-MRS) is a non-invasive magnetic resonance imaging technique that can quantify the concentration of multiple metabolites within the human brain. This review will outline recent applications of the complementary imaging techniques - fcMRI and ¹H-MRS - to improve our understanding of fibromyalgia pathophysiology and how pharmacological and non-pharmacological therapies contribute to analgesia in these patients. A better understanding of the brain in chronic pain, with specific linkage as to which neural processes relate to spontaneous pain perception and hyperalgesia, will greatly improve our ability to develop novel therapeutics. Neuroimaging will play a growing role in the translational research approaches needed to make this a reality.     

经颅电刺激镇痛研究的现状及展望

经颅电刺激技术是一种非侵入性神经调控方法,因其具有卓越的安全性、良好的患者依从性以及高度便携性等特点,被视为一种潜在的非药物镇痛手段。然而,目前对于经颅电刺激镇痛效果的研究结果不一致且镇痛机制尚未完全阐明。本文通过系统归纳总结3种主要的经颅电刺激技术——经颅直流电刺激、经颅交流电刺激和经颅随机噪声刺激——在镇痛领域的研究进展,评估了这些技术对短时、急性和慢性疼痛的镇痛效果,并深入剖析了其潜在的镇痛机制。同时,本文系统讨论了既往研究的局限性,并对未来研究提出了一系列切实可行的建议,如借助电场模拟技术实现个性化刺激以克服不同个体头部解剖结构差异的影响、应用多位点刺激和深部脑刺激技术来拓展刺激脑区、搭建经颅电刺激技术同步神经影像平台以制定个体特异性的刺激方案并深入揭示其镇痛机制、探索与其他治疗技术的联合应用以提高疗效等。这些建议的实施将有助于解决当前研究中存在的问题,充分发挥经颅电刺激在疼痛治疗中的临床价值,最终实现患者疼痛的缓解。     

Current methods of controlling post-operative pain.

Until recently, the clinical significance of post-surgical pain and its undertreatment were for the most part unappreciated. Recognition that inadequate analgesia adversely affects the patient's cardiovascular, pulmonary, and emotional status has spurred development of new and highly effective methods of controlling pain. With the introduction of spinal opioid and patient-controlled analgesia (PCA) came the realization that, while such forms of therapy provided superior pain relief, they were not without their own unique and occasionally serious side effects. For this reason, both techniques are more safely provided by highly trained members of a dedicated acute/post-surgical pain service. Although spinal opioid (epidural, intrathecal) techniques are invasive and require patient cooperation, they have a high degree of safety in low-risk populations (ASA 1 and 2). The major therapeutic advantage of spinal opioids is their ability to prevent pain from being perceived. PCA permits patients to titrate intravenous opioids in proportion to their particular level of pain intensity. Although PCA provides effective pain "relief," the technique is incapable of preventing pain from being appreciated. A number of studies have observed that pain scores in patients successfully employing PCA were significantly higher than those noted in individuals treated with epidural opioids. Nevertheless, the control gained by self-administration, uniformity of analgesia, and low level of adverse results associated with PCA provides higher patient satisfaction and decreased sedation when compared with traditional intramuscular dosing. The effectiveness of PCA may be improved by adjusting for patient variables, utilizing opioids having rapid onset, the addition of a basal infusion, and supplementation with non-steroidal anti-inflammatory agents. Interpleural analgesia represents an important therapeutic option in patients sensitive to opioid-induced respiratory depression. The technique is more effective when local anesthetic solutions are continually infused. Analgesic efficacy may be further enhanced by the addition of "low-dose" PCA.     

Platelet-Rich Plasma and the Elimination of Neuropathic Pain

Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events, starting with the induction of enhanced inflammation and its complete resolution, followed by all the subsequent steps of tissue remodeling, wound repair and axon regeneration that result in the elimination of neuropathic pain, and also by some of these same factors acting directly on neurons to promote axon regeneration thereby eliminating neuropathic pain.     

Occupational biomechanics of the neck: a review and recommendations.

Musculoskeletal disorders of the neck are becoming a major concern in industry. Several studies reported the association of neck pain, discomfort, and symptoms with different occupations in industry. Thus, the main objective of this study is to review and evaluate biomechanical techniques used in analyzing the occupational factors leading to neck pain and disorders. Recommendations for future research are also discussed.     

Wrist pain: a systematic approach to diagnosis

Numerous radiographic procedures are now available to help determine the cause of wrist pain. This paper presents a wrist-pain algorithm that defines the relative roles of various radiographic techniques in the evaluation of patients with wrist pain. Practical application of the algorithm is demonstrated through illustrative cases.     

Techniques for measuring the static and dynamic properties of the patella

An electrogomiometric method was used together with a new standardized radiographic technique to accurately determine the rotation of the patella during knee flexion of both normal subjects and patients referred for retropatellar pain. A preliminary study using these techniques shows that retropatellar pain is very much a multi-factoral clinical problem and that combinations of patello-femoral articulation abnormalities, patellar shape and mechanical influences are present in all forms of the painful patella.     

Coping with Phantom Limb Pain

Phantom limb pain is a chronic neuropathic pain that develops in 45–85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5–10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations. Chronic pain is physically and mentally debilitating, affecting an individual’s capacity for self-care, but also diminishing an individual’s daily capacity for personal and economic independence. In addition, the pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering from this condition. Although the pain can be reduced by antiepileptic drugs and analgesics, they are frequently ineffective or their side effects preclude their use. The optimal approach for eliminating neuropathic pain and improving individuals’ quality of life is the development of novel techniques that permanently prevent the development and maintenance of neuropathic pain, or that eliminate the pain once it has developed. What is still required is understanding when and where an effective novel technique must be applied, such as onto the nerve stump of the transected peripheral axons, dorsal root ganglion neurons, spinal cord, or cortex to induce the desired influences. This review, the second of two in this journal volume, examines the techniques that may be capable of reducing or eliminating chronic neuropathic pain once it has developed. Such an understanding will improve amputees’ quality of life by blocking the mechanisms that trigger and/or maintain PLP and chronic neuropathic pain.     

A System for Evaluating and Treating Chronic Back Disability

Five methods of personality assessment are evaluated to provide guidance for the psychological treatment of patients with chronic back pain. Patient pain drawings, pentothal pain studies, stress score index, psychological testing with the Minnesota Multiphasic Personality Inventory (MMPI) and response to treatment challenge are used as measurements for evaluation. This evaluation gives the treating staff guidelines for individual treatment programs utilizing operant conditioning techniques. Using this approach, three fourths of the severely disabled patients seen have been successfully treated.     

From inflammation to pain: experimental gene therapy

Chronic pain is frequently associated with profound alterations of neuronal systems involved in pain processing and should be considered as a real disease state of the nervous system. Unfortunately, some forms of chronic pain remain difficult to be satisfactorily treated. In the search for new therapeutic strategies, the gene-based approaches are of potential interest as they offer the possibility to introduce a therapeutic protein into some relevant structures and to drive its continuous production in the near vicinity of targeted cells. Recently, these techniques have been experimented in several animal models of chronic pain, showing that transfer at the spinal level of some genes, in particular those of opioid precursors proopiomelanocortin or proenkephalin A, leading to the overproduction of products that they encode, attenuated persistent pain of both inflammatory and neuropathic origin. Thus, in polyarthritic rat, a model of chronic inflammatory pain, we demonstrated that herpes simplex virus vector mediated overexpression of proenkephalin A in primary sensory neurons at the lumbar level elicited both antihyperalgesic and anti-inflammatory activities. Apart from opioids, numerous other molecules involved in pain processing are of potential therapeutic interest for gene-based protocols. For instance, targeting some molecules involved in pain induction and perpetuation, such as proinflammatory cytokines, raises an interesting possibility to block the "development" of pain. The clinical application of these approaches remains to be established, and, presently, one of the main problems to be solved is the innocuity of virus-derived vectors. However, the experimental use of gene-based techniques might be particularly useful for the evaluation of the therapeutic interest of some recently identified molecules involved in pain processing and might finally lead to the development of new "classical" pharmacological tools.     

A comparison of treatment modes in the management of myofascial pain dysfunction syndrome

This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature. Twenty-one females meeting specific criteria were randomly assigned to one of three treatment conditions: a dental splint and physiotherapy program; a relaxation program utilizing progressive muscle relaxation, biofeedback, and stress management techniques; or a minimal treatment program involving transcutaneous electrical nerve stimulation. Improvement was assessed through a dental examination, self-monitoring of pain, and an assessment of EMG activity during resting and task conditions. Significant changes were obtained in response to all treatment programs. The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain. The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw.     

Possibilities of hypnosis and hypnosuggestive methods in oncology

Fear of death, pain, or the recurrence of the illness of tumor patients can narrow their attention to a point where a spontaneous altered state of consciousness occurs. In these cases hypnosis either in formal psychotherapy or embedded into the everyday communication with the physician can effectively complement other already known medical and psychological techniques. Although numerous studies have reported the beneficial physical and mental changes induced by hypnosis, for a long time there were not enough research to affect evidence-based medicine. New studies meeting the most rigorous methodological standards, new reviews and the characteristics of hypnosis shown by neuroimaging techniques support the acceptance of this method. Hypnosis is used and studied with adult and child tumor patients alike mostly in the areas of anxiety, pain, nausea, vomiting, quality of life, mood amelioration, immune system and hot flushes. Most of the assays describe hypnosis as an empirically validated treatment technique that in most cases surpass attention diversion, coping trainings, cognitive behavior and relaxation techniques and other regular treatments. In this paper we review these observations.     

Magnetic resonance imaging for chronic pain: diagnosis,manipulation, and biomarkers

Pain is a multidimensional subjective experience with biological, psychological, and social factors. Whereas acute pain can be a warning signal for the body to avoid excessive injury, long-term and ongoing pain may be developed as chronic pain. There are more than 100 million people in China living with chronic pain, which has raised a huge socioeconomic burden. Studying the mechanisms of pain and developing effective analgesia approaches are important for basic and clinical research. Recently, with the development of brain imaging and data analytical approaches, the neural mechanisms of chronic pain have been widely studied. In the first part of this review, we briefly introduced the magnetic resonance imaging and conventional analytical approaches for brain imaging data. Then, we reviewed brain alterations caused by several chronic pain disorders, including localized and widespread primary pain, primary headaches and orofacial pain, musculoskeletal pain, and neuropathic pain, and present meta-analytical results to show brain regions associated with the pathophysiology of chronic pain. Next, we reviewed brain changes induced by pain interventions, such as pharmacotherapy, neuromodulation, and acupuncture. Lastly, we reviewed emerging studies that combined advanced machine learning and neuroimaging techniques to identify diagnostic, prognostic, and predictive biomarkers in chronic pain patients.     

Murine models of human neuropathic pain

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, and autoimmune diseases are examples of diseases that may cause neuropathic pain. Unfortunately no satisfactory treatment is yet available for this type of pain. This consideration has led to an explosion of interest for the underlying mechanisms, accompanied by a growing number of animal models. In recent years, most of the neuropathic pain models initially developed in the rat have been translated to mice in order to exploit the resource represented by genetically modified mice. Obviously the most useful animal models of pain would be ones in which the etiology of the pain would be endogenous and not induced by the experimenters: together with the classic models based on peripheral nerve ligation, in the last years other techniques are being developed that mimic more closely clinical pain syndromes, often by attempting to induce the disease associated to neuropathic pain. Although several variables must be taken into account when using animal models for mimicking clinical neuropathic pain, the huge number of models that are now reproducible and well characterized should help to reach important goals in the comprehension of mechanisms and to discover novel therapeutic target for this disease.     

Modulation of Central Nociceptive Coding by Acupoint Stimulation

It is universally accepted that acupuncture or acupoint stimulation can produce analgesic effect on patients with painful disorders. The past decades has seen remarkable progress in exploring the central mechanisms of acupuncture-induced pain relief, including the neurotransmitter release and expression of particular receptors and genes in the spinal cord and the brain stem regions. Development of new techniques makes it possible to record and image the brain network patterns underlying pain perception and modulation, and to investigate the role of higher-level brain areas in mediating acupuncture analgesia. This review will present the current understanding of the neural network that is implicated in the modulation of pain by acupuncture. Special issue article in honor of Dr. Ji-Sheng Han.     

Electroneuromyographic studies of pain sensitivity

We analyze the published information on the techniques of studies of pain sensitivity using objective electroneuromyographic approaches and the results of these studies. In particular, we describe works where the H reflex, nociceptive flexor and blinking reflexes, and exteroceptive suppression of voluntary muscle activity were examined. Some aspects of using somatosensory evoked potentials in the studies of pain phenomena are also discussed.     

Policy for controlling pain after surgery: effect of sequential changes in management.

OBJECTIVE--To observe the effects of introducing an acute pain service to the general surgical wards of a large teaching hospital. DESIGN--A study in seven stages: (1) an audit of current hospital practice succeeded by the sequential introduction to the general surgical wards of (2) pain assessment charts; (3) an algorithm to allow more frequent use of intramuscular analgesia; (4) increased use of local anaesthetic techniques of wound infiltration and nerve blocks; (5) an information sheet for patients about postoperative pain; (6) the introduction of patient controlled analgesia; (7) a repeat audit of hospital practice. Data were collected on each patient 24 hours after operation. SETTING--University Hospital of Wales, which has both district general and tertiary referral functions. PATIENTS--2035 patients over nine months from all surgical specialties (excluding cardiac) at the hospital. General surgical operations were studied in detail and separated into major, intermediate, and minor for data collection. MAIN OUTCOME MEASURES--A change in the median visual analogue pain scores 24 hours after surgery for pain during relaxation, pain on movement, and pain on deep inspiration at each stage of the study. RESULTS--There was a reduction in median visual analogue scores during the study. The median (95% confidence interval) scores for pain during relaxation decreased from 45 (34 to 53) in stage 1 to 16 (10 to 20) in stage 7 for major surgical procedures. Pain on movement decreased from 78 (66 to 80) to 46 (38 to 48), and pain on deep inspiration decreased from 64 (48 to 78) to 36 (31 to 38). The reductions in median scores for intermediate and minor operative procedures showed similar patterns. CONCLUSIONS--The introduction of an acute pain service to the general surgical wards led to considerable improvement in the level of postoperative pain as assessed by visual analogue scores. Simple techniques of regular pain assessment and the more frequent use of intramuscular analgesia as a result of using an algorithm were particularly effective.     

What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain?

Research suggests that fibromyalgia is a central, widespread pain syndrome supported by a generalized disturbance in central nervous system pain processing. Over the past decades, multiple lines of research have identified the locus for many functional, chronic pain disorders to the central nervous system, and the brain. In recent years, brain neuroimaging techniques have heralded a revolution in our understanding of chronic pain, as they have allowed researchers to non-invasively (or minimally invasively) evaluate human patients suffering from various pain disorders. While many neuroimaging techniques have been developed, growing interest in two specific imaging modalities has led to significant contributions to chronic pain research. For instance, resting functional connectivity magnetic resonance imaging (fcMRI) is a recent adaptation of fMRI that examines intrinsic brain connectivity - defined as synchronous oscillations of the fMRI signal that occurs in the resting basal state. Proton magnetic resonance spectroscopy (¹H-MRS) is a non-invasive magnetic resonance imaging technique that can quantify the concentration of multiple metabolites within the human brain. This review will outline recent applications of the complementary imaging techniques - fcMRI and ¹H-MRS - to improve our understanding of fibromyalgia pathophysiology and how pharmacological and non-pharmacological therapies contribute to analgesia in these patients. A better understanding of the brain in chronic pain, with specific linkage as to which neural processes relate to spontaneous pain perception and hyperalgesia, will greatly improve our ability to develop novel therapeutics. Neuroimaging will play a growing role in the translational research approaches needed to make this a reality.