Pain Research最新文献

{"title":"Role of macrophage–derived HMGB1 as an algogenic molecule ⁄ therapeutic target in visceral pain","authors":"Maho Tsubota, A. Kawabata","doi":"10.11154/PAIN.34.24","DOIUrl":"https://doi.org/10.11154/PAIN.34.24","url":null,"abstract":"Accumulating evidence sheds light on the crucial role of a neuroimmune crosstalk in neurogenic inflammation and diverse neurological diseases associated with neuro inflammation. High mobility group box 1 (HMGB 1 ), one of damage–associated molecular patterns (DAMPs) ⁄ alarmins, is now considered a pro–inflammatory ⁄ pro– nociceptive molecule, and participates in the pathogenesis of neuropathic and inflammatory pain. In this review, we focus on the role of HMGB 1 in visceral pain signaling in the bladder, pancreas and colon. In rodent models for cystitis–related bladder pain, macrophage–derived HMGB 1 activates the receptor for advanced glycation end– products (RAGE), and induces NF– κ B–dependent overexpression of cystathionine– γ –lyase, an H 2 S–generating enzyme, resulting in excessive excitation of nociceptors through the H 2 S ⁄ Ca v 3 . 2 T–type calcium channel pathway and subsequent bladder pain. The macrophage–derived HMGB 1 also appears to play a role in the development of pancreatic pain accompanying acute pancreatitis and of colonic pain in a mouse model for irritable bowel syndrome (IBS). Thus, HMGB 1 is considered a key mediator for a neuroimmune crosstalk involved in visceral pain signaling in the bladder, pancreas and colon, and may serve as a novel therapeutic target for treatment of visceral pain in patients with interstitial cystitis ⁄ bladder pain syndrome, acute pancreatitis or IBS.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48701918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pattern of cortical activation encodes subjective phantom limb movement","authors":"R. Fukuma, T. Yanagisawa, Masataka Tanaka, B. Seymour, K. Hosomi, H. Kishima, T. Yoshimine, Y. Kamitani, Y. Saitoh","doi":"10.11154/PAIN.34.39","DOIUrl":"https://doi.org/10.11154/PAIN.34.39","url":null,"abstract":"Subjective movability of phantom hand has been suggested to relate to phantom pain; however, cortical activities that represent the movement of phantom hand is unclear. Here, we recorded magnetoencephalographic signals while phantom limb patients moved their phantom hand and compared with the subjective movability of the phantom hand. During the experiment, the patients with phantom limb pain performed grasping and opening of phantom, and intact hands. Cortical potentials in the sensorimotor cortex contralateral to the tested hand were estimated from the magneto encephalographic signals, and used to infer movement type. Subjective movabili ty of the phantom hands were evaluated by duration of time required to perform grasping and opening. During movement of phantom hand, sensorimotor cortex contralateral to the phantom hand was activated similarly to the movement of intact hand. The decoding accuracy of movement type of phantom hand was deterio-rated in the patient who was not able to move his phantom hand fast. In conclusion, it was suggested that the decoding accuracy of phantom hand movement represented the subjective movability of the phantom hand.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.34.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42430594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual reality (VR) treatment for phantom limb pain","authors":"M. Sumitani, M. Osumi, Kazunori Inomata, Y. Otake, R. Inoue, Rikuhei Tsuchida, Yaeko Yokoshima, K. Azuma, H. Abe","doi":"10.11154/PAIN.34.19","DOIUrl":"https://doi.org/10.11154/PAIN.34.19","url":null,"abstract":"The brain monitors motor outputs and sensory inputs about limb movements and information communication of limb movements between the motor system and the sensory system all along the line. This information communication of limb move ments is called as the sensorimotor loop. In the normal condition, the sensorimotor loop maintains congruent. Recent advancement of cognitive neuroscience can propose that pathologic pain like as phantom limb pain can emerge and sustains and finally impairs patients’ quality of life when the loop becomes incongruent. We have treated phantom limb pain with the mirror visual feedback (MVF) and recently virtual reality (VR) treatment. The MVF and VR treatments can re–construct movement representations of a phantom limb and then improve phantom limb pain. We have successfully evaluated such movement representations of a phantom limb by assessing the intact upper limb movements on the basis of the bimanual coupling effect, which is physiologically equipped with the brain. The analgesic effect of the VR system is closely linked to the objectively–assessed reemergence of movement representations of a phantom limb.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44486823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of cortical motor representation and cortical excitability in refractory neuropathic pain","authors":"N. Mori, K. Hosomi, R. Takeuchi, Chanseok Lim, T. Mano, A. Matsugi, H. Kishima, Y. Saitoh","doi":"10.11154/PAIN.34.57","DOIUrl":"https://doi.org/10.11154/PAIN.34.57","url":null,"abstract":"Objective: Repetitive transcranial magnetic stimulation over the primary motor cortex has been shown to provide an analgesic effect on refractory neuropathic pain. It is thought that the primary motor cortex may be involved in pain–related cognitive processing. In this study, navigation–guided transcranial magnetic stimulation (TMS) was applied to investigate cortical motor representation and cortical excitability related to pain. Methods: Subjects were seven patients with refractory neuropathic pain (60.4 ± 13.5 years; stroke, n=5 ; peripheral nerve injury, n=1 ; brachial plexus avulsion, n=1). Pain intensity was measured using a visual analog scale, a numeric rating scale and the short–form McGill Pain Questionnaire 2 (SF–MPQ–2). We measured motor representation and cortical excitability assessed by motor evoked potentials with navigation–guided TMS around the primary motor cortex. A resting motor threshold (RMT), and motor map area and extent were measured in the both hemispheres. The relations between pain assessment items and each measurement (the RMT ratio of affected hemisphere (AH) to unaffected hemisphere (UH), AH ⁄ UH area ratio, and AH ⁄ UH extent ratio) were examined. Results : The RMT of AH trended to be higher than that of UH (p=0.07). The AH ⁄ UH area ratio significantly correlated to SF–MPQ2 (rs=−0.85, p=0.02). The other analyses showed no significant correlations between pain assessment items and each measurement with TMS. Conclusions: This study suggested that refractory neuropathic pain might lead to changes of cortical motor representation and cortical excitability.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44096331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging of microglia ⁄ macrophage in an animal model of peripheral inflammatory pain","authors":"H. Uchida, M. Abe, Kazuki Tainaka, K. Sakimura","doi":"10.11154/PAIN.34.31","DOIUrl":"https://doi.org/10.11154/PAIN.34.31","url":null,"abstract":"Microglia are parenchymal tissue–resident macrophage within the central nervous system (CNS) and originate from erythromyeloid precursor cells in the yolk sac. A growing body of evidence suggests that microglia engage in CNS development, homeostasis and diseases, including chronic pain. Peripheral nerve injury and inflammation produce persistent pain hypersensitivity via CNS sensitization, in which activated microglia have critical roles. Activation of microglia occurs at both spinal and supraspinal levels after nerve injury and inflammation; however, their spatial distribu-tion in the intact tissue remains poorly understood. Recently, tissue clearing methods and high–resolution imaging techniques have been greatly advanced, and these techniques will improve our understanding of pain mechanisms. Therefore, we attempted to clarify the three–dimensional localization of microglia in the intact CNS after peripheral inflammation by analyzing the reporter mouse line Iba– 1 (iCre/+); CAG– floxed STOP tdTomato with CUBIC (Clear, Unobstructed Brain ⁄ Body Imaging Cocktails and Computational analysis). In this review, we focus on recent advances in understanding of microglial activation under pathological pain conditions.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41395161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"第40回 日本疼痛学会  印象記  臨床部門","authors":"晃一 細見","doi":"10.11154/pain.33.325","DOIUrl":"https://doi.org/10.11154/pain.33.325","url":null,"abstract":"","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47216787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"第40回 日本疼痛学会  印象記  基礎部門","authors":"英二 金銅","doi":"10.11154/pain.33.323","DOIUrl":"https://doi.org/10.11154/pain.33.323","url":null,"abstract":"","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42588271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromodulation therapy for post–stroke pain","authors":"Takamitsu Yamamoto, Mitsuru Watanabe, Kazutaka Kobayashi, H. Oshima, C. Fukaya, A. Yoshino","doi":"10.11154/PAIN.33.294","DOIUrl":"https://doi.org/10.11154/PAIN.33.294","url":null,"abstract":"We have reported that 5 Hz cervical spinal cord stimulation (SCS) increased cerebral blood flow and induced muscle twitches in the upper extremities, and minimally conscious state patients showed a remarkable recovery of consciousness and motor function in the upper extremities compared with that in the lower extremities. From the findings of our previous study, we have applied 5 Hz cervical SCS in combination with conventional 20 Hz cervical SCS to induce paresthesia over the painful area in poststroke pain patients. We report a new SCS technique for post– stroke pain and motor weakness. Twenty–two poststroke pain patients underwent pharmacological evaluation and dual–lead SCS trials or implantation. For the pharmacological evaluation, ketamine, morphine, and thiopental tests were carried out. Using a Touhy needle, a four or eight–contact flexible cylinder–type electrode was inserted into the epidural space of the cervical or thoracic vertebrae. The patients received 5 Hz cervical SCS to induce muscle twitches for five minutes in one session, and five sessions per day were carried out. In addition, patients underwent 20Hz cervical SCS to induce paresthesia as much as they required. During the 20 Hz SCS test period in the 22 patients, pain relief was estimated as excellent (≧60% VAS score reduction) in six patients, good (30 – 59% reduction) in nine patients, fair (10 – 29% reduction) in four patients, and poor (<10% reduction) in three patients. Three patients with poor estimated pain relief were not treated with chronic SCS. Twenty–four months after chronic SCS in 19 patients, pain relief was estimated as excellent in three patients, good in nine patients, and fair in seven patients. The %VAS score reduction 24 months after chronic SCS and the results of the ketamine test showed a significant correlation (r=0.670, p=0.001) by Pearson’s correlation coefficient test. However, the %VAS score reduction and the thiopental (r=0.291, p=0.227) and morphine (r=0.327, p=0.172) tests showed no significant cor relation. In patients treated with a combination of cervical 5 Hz and 20 Hz SCS, the motor function of the upper extremities recovered remarkably. The pharmacological evaluation of poststroke pain is a useful tool for the selection of candidates for SCS, and low–dose ketamine drop infusion method is useful for increasing the effect of SCS. The combination of 5 Hz and 20 Hz SCS is a new neuro-","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43995259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a macaque model of central post–stroke pain and challenges to understand the mechanisms","authors":"N. Higo, K. Nagasaka","doi":"10.11154/PAIN.33.275","DOIUrl":"https://doi.org/10.11154/PAIN.33.275","url":null,"abstract":"Central post–stroke pain (CPSP) is a central neuropathic pain characterized by pain and sensory abnormalities due to central nervous system lesion following a cerebro vascular accident. Developing therapeutic interventions for CPSP is difficult because its pathophysiology is unclear. In recent years, rodent models of CPSP have been developed to address this problem. In these models, a lesion of the thalamus including the ventral posterolateral nucleus (VPL) was made by inducing a focal stroke. Using these models, cellular and molecular mechanisms that underlie pathogenesis of CPSP have been discovered. Moreover, some drugs have been suggested to ameliorate the symptoms of the rodent CPSP models. In addition to the rodent models, a primate model of CPSP might also contribute to overcoming CPSP because it is more com-patible with humans in regard to the structures and functions of brain regions which is suggested to be involved in pain in humans. Aside from humans, the macaque monkeys are the most widespread primate genus, ranging from Japan to North Africa. Since the macaque monkeys are the animal species closest to humans among those which can be used for invasive experiments, they are widely used to understand the mechanisms of the human brain. Therefore, we developed a nonhuman primate model of CPSP using macaque monkeys. Because there were individual differences among macaque monkeys, the location of the VPL in each monkey was determined by magnetic resonance imaging (MRI) and extracellular recording of neuronal activity during tactile stimulation. Thereafter, a hemorrhagic lesion was induced by injecting collagenase type IV. Histological analysis using Nissl staining revealed that most of the lesion was localized within the VPL. Several weeks after the injection, the macaques displayed behavioral changes that were interpreted as reflecting the development of both mechanical allodynia and thermal hyperalgesia. functional magnetic resonance imaging is performed to detect brain activity changes underlying CPSP using the established macaque model. The combination of the homology of pain–related cortical areas between macaques and humans with relative-ly large macaque brain enables acquisition of imaging data on par with those examined in clinical research. Therefore, the brain imaging studies using the macaque monkey provide an advantage for the translation of the findings to human patients. We believe that animal models of CPSP will contribute not only to full understanding of pathophysiology but also to the development of therapeutic interventions for it.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48425827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic itch by neuron–glia interactions in the spinal dorsal horn","authors":"M. Tsuda","doi":"10.11154/PAIN.33.302","DOIUrl":"https://doi.org/10.11154/PAIN.33.302","url":null,"abstract":"Itch sensation is a defense system that responds rapidly to a wide range of harmful internal and external stimuli. Recent progress in our understanding of the neuronal basis for itch sensation in the nervous systems has been made, but the mechanism underly ing how itch turns into a pathological chronic state, such as atopic dermatitis, remains poorly understood. It is becoming clear that chronic itch is not simply a con-sequence of the continuity of acute itch signals, but rather of maladaptive function in the nervous system that is caused by long–term structural and functional alterations following skin inflammation. Recent studies have uncovered the causal role of glial cells in the spinal dorsal horn using mouse models of chronic itch including atopic dermatitis. Understanding the key roles of neuron–glia interactions may provide us with exciting insights into the mechanisms for the chronicity of itch and clues to develop novel therapeutic agents for treating chronic itch.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47499535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}