癌症痛的神经生物学机制研究进展

癌症痛是影响癌症病人生活质量的一个严重问题 ,但长期以来由于缺乏合适的动物模型 ,对其神经机制的研究甚少。近年出现的小鼠股骨、跟骨、肱骨和大鼠胫骨癌症痛模型 ,极大地推动了癌症痛的基础研究。初步研究表明 ,癌症痛有其独特的神经化学机制 ,骨质破坏、外周敏化、中枢敏化及神经侵蚀都参与了癌症痛的产生。本文综述了癌症痛动物模型、癌症痛的产生机制及其药物治疗等方面的研究进展。     

Glutamate transporter: an unexpected target for some antibiotics

Molecular pain is a relatively new and rapidly expanding research field that represents an advanced step from conventional pain research. Molecular pain research addresses physiological and pathological pain at the cellular, subcellular and molecular levels. These studies integrate pain research with molecular biology, genomics, proteomics, modern electrophysiology and neurobiology. The field of molecular pain research has been rapidly expanding in the recent years, and has great promise for the identification of highly specific and effective targets for the treatment of intractable pain. Although several existing journals publish articles on classical pain research, none are specifically dedicated to molecular pain research. Therefore, a new journal focused on molecular pain research is needed. Molecular Pain, an Open Access, peer-reviewed, online journal, will provide a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.     

Stem cells for the treatment of musculoskeletal pain

Musculoskeletal-related pain is one of the most disabling health conditions affecting more than one third of the adult population worldwide. Pain from various mechanisms and origins is currently underdiagnosed and undertreated. The complexity of molecular mechanisms correlating pain and the progression of musculoskeletal diseases is not yet fully understood. Molecular biomarkers for objective evaluation and treatment follow-up are needed as a step towards targeted treatment of pain as a symptom or as a disease. Stem cell therapy is already under investigation for the treatment of different types of musculoskeletal-related pain. Mesenchymal stem cell-based therapies are already being tested in various clinical trials that use musculoskeletal system-related pain as the primary or secondary endpoint. Genetically engineered stem cells, as well as induced pluripotent stem cells, offer promising novel perspectives for pain treatment. It is possible that a more focused approach and reassessment of therapeutic goals will contribute to the overall efficacy, as well as to the clinical acceptance of regenerative medicine therapies. This article briefly describes the principal types of musculoskeletal-related pain and reviews the stem cell-based therapies that have been specifically designed for its treatment.     

Where's the ecology in molecular ecology?

Molecular techniques have had a profound impact in biology. Major disciplines, including evolutionary biology, now consistently utilize molecular tools. In contrast, molecular techniques have had a more limited impact in ecology. This discrepancy is surprising. Here, we describe the unexpected paucity of ecological research in the field colloquially referred to as 'molecular ecology.' Publications over the past 15 years from the journals Ecology , Evolution and Molecular Ecology reveal that much of the research published under the molecular ecology banner is in fact evolutionary in nature, and that comparatively little ecological research incorporates molecular tools. This failure to more broadly utilize molecular techniques in ecology is alarming because several promising lines of ecological inquiry could benefit from molecular approaches. Here we summarize the use of molecular tools in ecology and evolution, and suggest several ways to renew the ecological focus in 'molecular ecology'.     

Recent advances in basic neurosciences and brain disease: from synapses to behavior

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007).     

Pain in Parkinson′s Disease: A Cross-Sectional Study of Its Prevalence,Types, and Relationship to Depression and Quality of Life

Pain is an important and distressing symptom in Parkinson’s disease (PD). Our aim was to determine the prevalence of pain, its various types and characteristics, as well as its impact on depression and quality of life (QoL) in patients with PD. How pain differs in early- and advanced-stage PD and male and female PD patients was of special interest. One hundred PD patients on dopaminergic medications had a neurological examination and participated in a structured interview on pain characteristics and completed standardized questionnaires. A total of 76% of the patients had pain. The following types of pain were present: musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%, central neuropathic pain for 22%, radicular pain for 27%, and other pains (non-radicular low back pain, arthritic, and visceral pain) made up 24%. One type of pain affected 29% of all the subjects, two types 35%, three types 10%, and four types of pain were reported by 2%. All types of pain were more prevalent in advanced-stage PD subjects than in early-stage PD subjects, except for arthritic pain (subclassified under”other pain”). The frequency and intensity of actual, average, and worst experienced pain were significantly more severe in advanced-stage subjects. PD subjects with general pain and in advanced stages were more depressed and had poorer QoL. Depression correlated with worst pain in the last 24 hours and with pain periodicity (the worst depression score in patients with constant pain). QoL correlated with average pain in the last 7 days. Pain is a frequent problem in PD patients, and it worsens during the course of the disease.     

不同量表用于机械通气新生儿急性疼痛评估的价值分析

目的:分析和比较不同量表用于机械通气新生儿急性疼痛评估的价值。方法:使用总结性、回顾性研究方法,研究时间为2017年3月份到2018年7月份,选择在医院NICU接受机械通气诊治的新生儿56例作为研究对象,所有新生儿都给予高频震荡通气治疗,急性疼痛采用新生儿疼痛/激惹与镇静量表、新生儿急性疼痛评估量表进行评估与分析,记录评估效果。结果:新生儿疼痛/激惹与镇静量表的总体Cronbachα系数为0.698分,最高评分为基础行为状态,最低评分为心率增快。新生儿急性疼痛评估量表的内部一致性总体Cronbachα系数为0.822,最高评分为胎龄,最低评分为SaO2。新生儿疼痛/激惹与镇静量表的护理人员一致性组内相关系数(ICC)为0.992,新生儿急性疼痛评估量表的护理人员一致性组内相关系数ICC为0.987。以新生儿疼痛/激惹与镇静量表作为效标,新生儿急性疼痛评估量表的效标关联效度Spearman相关系数为r=0.855,P=0.007。12名护理人员对新生儿急性疼痛评估量表的选择率为66.7%,对新生儿疼痛/激惹与镇静量表的选择率为33.3%。结论:新生儿疼痛/激惹与镇静量表和新生儿急性疼痛评估量表在机械通气新生儿急性疼痛评估中都有很好的信度与一致性,其中新生儿急性疼痛评估量表的可行性和临床实用性更好。     

Barriers to assessment and treatment of pain in laboratory animals

Pain is an undesirable potential consequence of many of the procedures conducted on animals in the course of scientific research, and in most cases it is unnecessary. The US Congress, the public, and laboratory animal medical professionals have indicated that pain should be prevented or minimized in laboratory animals, yet there is ample evidence to suggest that unalleviated pain is still a problem for some laboratory animals. This evidence is circumstantial to some extent but has its basis in problematic issues of pain control in both veterinary and human medicine. The author attempts to identify specific barriers to reduction of pain in laboratory animals. She then seeks to determine the relative importance of each obstacle and to develop approaches to overcoming each obstacle.     

New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review

Pain is an unpleasant sensory and emotional experience that is commonly associated with actual or potential tissue damage. Despite decades of pain research, many patients continue to suffer from chronic pain that is refractory to current treatments. Accumulating evidence has indicated an important role of protease-activated receptor 4 (PAR4) in the pathogenesis of inflammation and neuropathic pain. Here we reviewed PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. Understanding PAR4 and its corresponding signaling pathways will provide insight to further explore the molecular basis of pain, which will also help to identify new targets for pharmacological intervention for pain relief.     

New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review

Pain is an unpleasant sensory and emotional experience that is commonly associated with actual or potential tissue damage. Despite decades of pain research, many patients continue to suffer from chronic pain that is refractory to current treatments. Accumulating evidence has indicated an important role of protease-activated receptor 4 (PAR4) in the pathogenesis of inflammation and neuropathic pain. Here we reviewed PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. Understanding PAR4 and its corresponding signaling pathways will provide insight to further explore the molecular basis of pain, which will also help to identify new targets for pharmacological intervention for pain relief.     

Pain detection and amelioration in animals on the farm: issues and options

Pain in nonhuman animals is a difficult concept to identify and measure. This article briefly describes the consequences of pain in animals on the farm and explains the reasons for the minimal use of analgesics in farmed animals. Pain can have implications for both animal welfare and economics. The reasons for a low use of analgesics in farmed animals include the lack of recognition of animal pain owing to the apparent lack of anthropomorphically identifiable behavioral changes, concern over human food safety, and lack of research efforts to develop safe analgesics for farm use. Treatment cost relative to the benefits expected is another hindering factor. Interventions to minimize pain must begin with developing objective and practical measures for pain identification and measurement at the farm level. A suggested use of a combination of different behavioral and physiological indicators would help to identify pain in animals. To facilitate continued usage of the methodologies on the farm it also is necessary to evaluate the economic implication of the pain alleviation intervention.     

Pain Detection and Amelioration in Animals on the Farm: Issues and Options

Pain in nonhuman animals is a difficult concept to identify and measure. This article briefly describes the consequences of pain in animals on the farm and explains the reasons for the minimal use of analgesics in farmed animals. Pain can have implications for both animal welfare and economics. The reasons for a low use of analgesics in farmed animals include the lack of recognition of animal pain owing to the apparent lack of anthropomorphically identifiable behavioral changes, concern over human food safety, and lack of research efforts to develop safe analgesics for farm use. Treatment cost relative to the benefits expected is another hindering factor. Interventions to minimize pain must begin with developing objective and practical measures for pain identification and measurement at the farm level. A suggested use of a combination of different behavioral and physiological indicators would help to identify pain in animals. To facilitate continued usage of the methodologies on the farm it also is necessary to evaluate the economic implication of the pain alleviation intervention.     

An approach to localizing corneal pain representation in human primary somatosensory cortex

The cornea has been a focus of animal electrophysiological research for decades, but little is known regarding its cortical representation in the human brain. This study attempts to localize the somatotopic representation of the cornea to painful stimuli in human primary somatosensory cortex using functional magnetic resonance imaging (fMRI). In this case study, a subject was imaged at 3T while bright light was presented in a block-design, which either produced pain and blinking (during photophobia) or blinking alone (after recovery from photophobia). Pain and blinking produced precisely localized activations in primary somatosensory cortex and primary motor cortex. These results indicate that noxious stimulation of the cornea can produce somatotopic activation in primary somatosensory cortex. This finding opens future avenues of research to evaluate the relationship between corneal pain and central brain mechanisms relating to the development of chronic pain conditions, such as dry eye-like symptoms.     

The Effect of Animal-Assisted Therapy on Pain Medication Use After Joint Replacement

Animal-assisted therapy (AAT) has been used in a variety of healthcare settings and studies to evaluate the potential patient benefits are warranted. This retrospective study measured the impact of AAT on the use of oral pain medications by adults after total joint replacement surgery. One group of patients received care in a hospital with an AAT program and the comparison group was in a hospital without an AAT program. Adult patient cohorts were matched on: age, gender, ethnicity, length of stay, and Diagnosis Related Group code for type of total joint replacement. Pain medication doses, converted into morphine equivalent daily doses (MEDD), were compared. Pain medication use was significantly less in the AAT group: 15.32 mg vs. 21.16 (t₍₁₁₉₎ = 2.72, p = 0.007). The effectiveness of AAT in decreasing the need for pain medication and its effect on patient well-being in the post-operative period and in other settings deserves further study.     

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.     

On the enigma of pain and hyperalgesia: A molecular perspective

Pain is a common symptom of injuries and inflammatory-related conditions. The perception of pain, commonly known as nociception, depends on integrated receptors and molecular pathways. Inflammatory mediators are involved in the genesis, persistence, and severity of pain. Noxious stimuli can trigger a cascade of inflammatory loops that feedback onto sensory modalities and domains of the CNS, in an attempt to alert the brain of deregulated homeostasis. Understanding the mechanisms of pain continue to make nociception and hyperalgesia a burgeoning field of research.     

Ionic channels and neuropathic pain: physiopathology and applications

Neuropathic pain is defined by the International Association for Pain research as a pain associated to a primary lesion or a dysfunction of the central or peripheral system. Over the past few years the causes of the neuropathic pain were not known and there were not good treatments for it, now we have a better knowledge of the physiopathological aspects and there is a wider diffusion of the research for target aimed therapies. The physiologic genesis of nervous messages occurs exclusively in skin sensorial endings or in nerve tissues as a consequence of an adequate sensorial stimulus and depends on the quick variations of the electric potential difference at the endings of ionic membranes. These variations of even 500 V a second are possible because of the presence of ionic channels. In neuropathic pain impulses can be originated even from ectopic sites. Ectopic discharges originated in a peripheral neuropathic system have an important role in the early stage of neuropathic pain development in two different ways. First they give an excess of spontaneous and evoked electric impulses to the central nervous system, causing a primitive neuropathic pain signal; then the ectopic activity develops and maintains the central sensitisation process. All this amplifies the afferent signals deriving from residual efferents that go on innerving cutaneous areas damaged and partly disnerved, causing tactile allodynie. Sodium channels are the greatest responsible for electrogenesis, that is the basis of the action potential generation and its propagation. Action potential begins after a depolarization such that it could cause a membrane transitory modification, turning prevalently permeable to Na+ more than to K+ as during a release phase. Neuropathy generates a local accumulation of sodium channels, with a consequent increase of density. This remodel seems to be the basis of neuro hyperexecitably. Calcium channels have also an important role in cell working. Intracellular calcium increase contributes to depolarization processes, through kinase and determines the phosphorylation of membrane proteins that can make powerful the efficacy of the channels themselves. In the future new diagnostic opportunities of physiopathologist mechanism leading to neuropathic pain will allow treatments aimed at specific molecular changes of ionic channels.     

Electrodermal Activity at Acupuncture Points Differentiates Patients with Current Pain from Pain-Free Controls

This study evaluated whether electrodermal resistance at acupuncture points (AP) systematically varies as a function of pain. The study was conceived as a proof-of-principle study in support of research on acupuncture and other complementary medicine approaches. Specifically, this study investigates whether or not electrodermal activity systematically differentiates arthritis patients with current pain from pain-free controls. Participants with rheumatoid arthritis (n = 32) and a typical pain level of at least 3 (on a 0–10 scale) were compared with case controls (n = 28) who had no medical diagnosis and were pain free. Electrodermal resistance at AP was measured with a commercial ohmmeter and compared to heart rate, blood pressure, and ratings on the Pain Catastrophization Scale and the McGill Melzack Pain Questionnaire. There were consistent differences between the experimental group and the control group on all markers of pain. Similarly, there were significant group differences and some trends for electrodermal activity at the AP labeled ‘bladder,’ ‘gall bladder,’ and ‘small intestine.’ It is concluded that the concept of electrodermal resistance at AP possesses criterion validity for distinguishing pain from a no pain state. This research provides support for the usefulness of measuring electrodermal activity when testing energy-based models of disease, and can be seen as a bridge between Western and Chinese medicine.     

Pain control by ionizing radiation of bone metastasis

Pain treatment due to cancer is a large fraction of the care in a radiotherapy department. While radiation treatment is very effective in reducing pain, the pathophysiology of bone metastases remains very complex. Reducing the number of tumour cells by radiation will reduce the pressure in bone marrow, but the very rapid response to radiation treatment seen in some patients is probably related to the presence of highly radiosensitive inflammatory cells. In this review we give an overview of the pathophysiological mechanisms which lead to pain associated with bone metastasis and the impact of radiation treatment and other treatments on this mechanism.