K. Hosomi, Takeshi Shimizu, Y. Goto, T. Mano, S. Oshino, H. Kishima, Y. Saitoh
Central poststroke pain (CPSP) is one of the most refractory neuropathic pain, and this condition is typically pharmacoresistant. Owing to the refractory nature of CPSP, neuromodulation therapies such as deep brain stimulation (DBS), electrical motor cortex stimulation (EMCS), repetitive transcranial magnetic stimulation (rTMS), and spinal cord stimulation (SCS) have been applied to treating for CPSP. This paper briefly describes profiles of CPSP, and reviews previous reports of each neuromodulation therapy, including our clinical experience. The long–term success rate of DBS of the sensory thalamus or periaqueductal grey matter has been reported to be about 30 % from 92 CPSP cases, while EMCS is most efficient, about 50 % success rate from 142 cases, in the invasive neuromodulation therapies. Recent meta–analyses and therapeutic guidelines reported that high–frequency rTMS of the primary motor cortex was safe and had transient pain relieving effect. rTMS is currently the preferred treatment approach, but must be applied repeatedly for clinical practice. Although SCS was previously believed to be ineffective for CPSP, it can be applied to CPSP because some CPSP cases actually respond to SCS. A greater understanding of the pathophysiology of CPSP and mechanisms of action of neuromodulation therapies could lead more–efficient targets and treatments.
{"title":"Neuromodulation therapies for central poststroke pain","authors":"K. Hosomi, Takeshi Shimizu, Y. Goto, T. Mano, S. Oshino, H. Kishima, Y. Saitoh","doi":"10.11154/PAIN.33.18","DOIUrl":"https://doi.org/10.11154/PAIN.33.18","url":null,"abstract":"Central poststroke pain (CPSP) is one of the most refractory neuropathic pain, and this condition is typically pharmacoresistant. Owing to the refractory nature of CPSP, neuromodulation therapies such as deep brain stimulation (DBS), electrical motor cortex stimulation (EMCS), repetitive transcranial magnetic stimulation (rTMS), and spinal cord stimulation (SCS) have been applied to treating for CPSP. This paper briefly describes profiles of CPSP, and reviews previous reports of each neuromodulation therapy, including our clinical experience. The long–term success rate of DBS of the sensory thalamus or periaqueductal grey matter has been reported to be about 30 % from 92 CPSP cases, while EMCS is most efficient, about 50 % success rate from 142 cases, in the invasive neuromodulation therapies. Recent meta–analyses and therapeutic guidelines reported that high–frequency rTMS of the primary motor cortex was safe and had transient pain relieving effect. rTMS is currently the preferred treatment approach, but must be applied repeatedly for clinical practice. Although SCS was previously believed to be ineffective for CPSP, it can be applied to CPSP because some CPSP cases actually respond to SCS. A greater understanding of the pathophysiology of CPSP and mechanisms of action of neuromodulation therapies could lead more–efficient targets and treatments.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"18-25"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41899153","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}
A. Nakae, T. Soshi, Yumi Tsugita, Chie Kishimoto, Kosuke Kato
Background & goal of the study. International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience which leads to the concept that pain is subjective. Everyone must agree that doctors have to treat patients’ pain if they say that they feel severe pain. However, doctors sometimes encounter problems due to lack of objective evaluation methods of pain. For example, even after the doctor has administered full strength of the medicine for the specific patient for the pain he/she is experiencing, the patient at times still remain unsatisfied. This is because patients are not always able to tell that the medicine has already taken effect. To evaluate patients’ pain correctly, objective evaluation methods should be developed. The goal of the study is to develop a way to evaluate the sharp, momentary pain objectively using electroencephalogram (EEG). Methods. After signing the written informed consent, 20 healthy volunteers attended the study. Five different thermal stimuli (selected from 40, 42, 44, 46, 48, 50°C stimulus based on individual heat pain tolerance data) were applied randomly using PATHWAY (Medoc Co Ltd., Israel). Participants’ subjective evaluation of pain was done using Visual Analog Scale (VAS). Moreover, participants were randomly subjected to 20 pairs of the above mentioned stimuli. The relative rating scale of subjective pain for each thermal stimulus was used as subjective evaluation. Rating were based on the subjective declaration of ("–3 : The former is very painful" "0 : Neither can you say" "+3 : the latter is very painful"), the pairing comparison method of Chefe Method used for scale. Results. In the thermal stimulation, half of the participants showed over 0.6 of R2 value which means correlation coefficient between relative pain scale and amplitude extracted from EEG data. Discrimination rates between maximum stimulation and middle stimulation was 80%, middle stimulation and minimum stimulation also 80% based on subjective evaluation and fluctuation of amplitude data. Discussion. A close relationship between the stimulation intensity and EEG data is clarified. Objective discrimination of pain can be developed using EEG, and in particul ar, it must be useful for patients who cannot describe the amount of pain they are experiencing properly.
研究背景与目的。国际疼痛研究协会将疼痛定义为一种不愉快的感觉和情感体验，这导致了疼痛是主观的概念。每个人都必须同意，如果医生说他们感到剧烈疼痛，他们必须治疗病人的疼痛。然而，由于缺乏客观的疼痛评估方法，医生有时会遇到问题。例如，即使在医生给特定的病人服用了他/她正在经历的疼痛的全部药物后，病人有时仍然不满意。这是因为患者并不总是能够知道药物已经生效。要正确评价患者的疼痛，需要建立客观的评价方法。本研究的目的是建立一种利用脑电图(EEG)客观评价瞬间性痛觉的方法。方法。在签署书面知情同意书后，20名健康志愿者参加了这项研究。使用PATHWAY (Medoc Co Ltd, Israel)随机应用5种不同的热刺激(根据个体热痛耐受性数据从40、42、44、46、48和50°C的刺激中选择)。采用视觉模拟量表(VAS)对疼痛进行主观评价。此外，参与者还随机接受了20对上述刺激。采用主观疼痛相对评定量表对各热刺激进行主观评价。评分基于主观声明(“-3:前者很痛苦”“0:你也说不出来”“+3:后者很痛苦”)，采用厨师法的配对比较法进行评分。结果。在热刺激中，有一半的参与者表现出超过0.6的R2值，即从EEG数据中提取的相对疼痛量表与振幅之间的相关系数。根据主观评价和振幅数据波动，最大刺激和中刺激的区分率为80%，中刺激和最小刺激的区分率为80%。讨论。阐明了刺激强度与脑电图数据之间的密切关系。利用脑电图可以发展对疼痛的客观辨别，特别是，它必须对那些不能正确描述他们所经历的疼痛程度的患者有用。
{"title":"Objective evaluation of pain using experimental heat stimulation","authors":"A. Nakae, T. Soshi, Yumi Tsugita, Chie Kishimoto, Kosuke Kato","doi":"10.11154/PAIN.33.40","DOIUrl":"https://doi.org/10.11154/PAIN.33.40","url":null,"abstract":"Background & goal of the study. International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience which leads to the concept that pain is subjective. Everyone must agree that doctors have to treat patients’ pain if they say that they feel severe pain. However, doctors sometimes encounter problems due to lack of objective evaluation methods of pain. For example, even after the doctor has administered full strength of the medicine for the specific patient for the pain he/she is experiencing, the patient at times still remain unsatisfied. This is because patients are not always able to tell that the medicine has already taken effect. To evaluate patients’ pain correctly, objective evaluation methods should be developed. The goal of the study is to develop a way to evaluate the sharp, momentary pain objectively using electroencephalogram (EEG). Methods. After signing the written informed consent, 20 healthy volunteers attended the study. Five different thermal stimuli (selected from 40, 42, 44, 46, 48, 50°C stimulus based on individual heat pain tolerance data) were applied randomly using PATHWAY (Medoc Co Ltd., Israel). Participants’ subjective evaluation of pain was done using Visual Analog Scale (VAS). Moreover, participants were randomly subjected to 20 pairs of the above mentioned stimuli. The relative rating scale of subjective pain for each thermal stimulus was used as subjective evaluation. Rating were based on the subjective declaration of (\"–3 : The former is very painful\" \"0 : Neither can you say\" \"+3 : the latter is very painful\"), the pairing comparison method of Chefe Method used for scale. Results. In the thermal stimulation, half of the participants showed over 0.6 of R2 value which means correlation coefficient between relative pain scale and amplitude extracted from EEG data. Discrimination rates between maximum stimulation and middle stimulation was 80%, middle stimulation and minimum stimulation also 80% based on subjective evaluation and fluctuation of amplitude data. Discussion. A close relationship between the stimulation intensity and EEG data is clarified. Objective discrimination of pain can be developed using EEG, and in particul ar, it must be useful for patients who cannot describe the amount of pain they are experiencing properly.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"40-46"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47851871","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}
Yasunori Takayama, K. Shibasaki, H. Furue, D. Uta, M. Tominaga
A calcium–activated chloride channel, anoctamin 1 (ANO1), is strongly activated by intracellular calcium increases through activation of transient receptor potential (TRP) channel because these ion channels physically interact with one another on the plasma membrane. The functional inter action occurs when TRP channels and ANO1 are within 20 nm, although ANO1 could be activated by global calcium increases as well. Recently, we obtained data that suggested the significance of the inter actions in the choroid plexus and primary sensory neurons. TRPV4 and ANO1 inter action in the apical membrane of choroid plexus epithelial cells could induce water efflux to the ventricle side. This interaction could be important in the homeostatic release of cerebro spinal fluid. That is, TRPV4 could be activated by the combined effects of body temperature and membrane stretch evoked by continuous water influx from the basolateral (capillary) side. Furthermore, TRPV1 and ANO1 inter action enhances TRPV1–mediated pain sensation. TRPV1 and ANO1 are co–expressed in small dorsal root ganglion (DRG) neurons. In our study, ANO1 current was induced by capsaicin application in small DRG neurons. ANO1–dependent depolarization following TRPV1 activation evoked action potentials. Furthermore, capsaicin–evoked pain–related behaviors in mice were strongly inhibited by a selective ANO1 blocker whereas the compound did not completely abolish the behaviors. The significance of these observations is that selective ANO1 inhibi tion reduces pain sensation. We also investigated non–specific inhibitory effects of chemicals on ion channel activities. We recently found that 4–isopropylcyclohexanol (4–iPr–CyH–OH) has an analgesic effect on burning pain sensation. 4–iPr–CyH–OH, a menthol analogue, is an aliphatic higher alcohol and used as a food– or flavor–additive. This compound inhibits TRPV1 and ANO1 without agonistic effects on TRPV1, TRPA1 or ANO1. Menthol also inhibits TRPV1 and ANO1, however, the TRPM8 agonist activates TRPA1 followed by pain sensation. Therefore, 4–iPr–CyH–OH might be a novel analgesia, Symposium 3 : The 39th Annual Meeting of JASP
{"title":"Physiological significances of TRP–ANO1 interaction","authors":"Yasunori Takayama, K. Shibasaki, H. Furue, D. Uta, M. Tominaga","doi":"10.11154/PAIN.33.1","DOIUrl":"https://doi.org/10.11154/PAIN.33.1","url":null,"abstract":"A calcium–activated chloride channel, anoctamin 1 (ANO1), is strongly activated by intracellular calcium increases through activation of transient receptor potential (TRP) channel because these ion channels physically interact with one another on the plasma membrane. The functional inter action occurs when TRP channels and ANO1 are within 20 nm, although ANO1 could be activated by global calcium increases as well. Recently, we obtained data that suggested the significance of the inter actions in the choroid plexus and primary sensory neurons. TRPV4 and ANO1 inter action in the apical membrane of choroid plexus epithelial cells could induce water efflux to the ventricle side. This interaction could be important in the homeostatic release of cerebro spinal fluid. That is, TRPV4 could be activated by the combined effects of body temperature and membrane stretch evoked by continuous water influx from the basolateral (capillary) side. Furthermore, TRPV1 and ANO1 inter action enhances TRPV1–mediated pain sensation. TRPV1 and ANO1 are co–expressed in small dorsal root ganglion (DRG) neurons. In our study, ANO1 current was induced by capsaicin application in small DRG neurons. ANO1–dependent depolarization following TRPV1 activation evoked action potentials. Furthermore, capsaicin–evoked pain–related behaviors in mice were strongly inhibited by a selective ANO1 blocker whereas the compound did not completely abolish the behaviors. The significance of these observations is that selective ANO1 inhibi tion reduces pain sensation. We also investigated non–specific inhibitory effects of chemicals on ion channel activities. We recently found that 4–isopropylcyclohexanol (4–iPr–CyH–OH) has an analgesic effect on burning pain sensation. 4–iPr–CyH–OH, a menthol analogue, is an aliphatic higher alcohol and used as a food– or flavor–additive. This compound inhibits TRPV1 and ANO1 without agonistic effects on TRPV1, TRPA1 or ANO1. Menthol also inhibits TRPV1 and ANO1, however, the TRPM8 agonist activates TRPA1 followed by pain sensation. Therefore, 4–iPr–CyH–OH might be a novel analgesia, Symposium 3 : The 39th Annual Meeting of JASP","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44598292","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}
T. Yanagisawa, R. Fukuma, Seymour Ben, K. Hosomi, Takeshi Shimizu, H. Kishima, M. Hirata, H. Yokoi, T. Yoshimine, Y. Kamitani, Y. Saitoh
Objectives. Phantom limb pain is neuropathic pain after amputation of a limb and partial or complete deafferentation such as brachial plexus root avulsion. The underlying cause of this pain has been attributed to maladaptive plasticity of the sensorimotor cortex. It has been suggested that experimental reorganization would affect pain. Here, we tested the hypothesis that a training to use brain–machine interface (BMI) based on magnetoencephalographic (MEG) signals will induce some cortical plasticity in the sensorimotor cortex and modulate the phantom limb pain. Methods. This study included 10 phantom limb patients (9 brachial plexus root avulsion and 1 amputee). MEG signals during movements of the phantom hand or intact hand were used to train the decoder inferring movements of each hand. The robotic hand was controlled by the decoder. Patients controlled the robotic hand by moving the phantom hand. The training effects were compared among trainings with the phantom decoder, real hand decoder, and random decoder in a randomized cross– over trial. Results. BMI training with the phantom decoder increased the decoding accuracy of phantom hand movements and pain. In contrast, BMI training with the intact hand decoder reduced accuracy and pain. Discussion. It was suggested that BMI training to modulate the motor representation of phantom hand controlled pain. The sensorimotor cortical plasticity might induce pain. Symposium 4 : The 39th Annual Meeting of JASP
{"title":"Induction of cortical plasticity reveals the mechanism of the phantom limb pain and develops novel treatment","authors":"T. Yanagisawa, R. Fukuma, Seymour Ben, K. Hosomi, Takeshi Shimizu, H. Kishima, M. Hirata, H. Yokoi, T. Yoshimine, Y. Kamitani, Y. Saitoh","doi":"10.11154/PAIN.33.26","DOIUrl":"https://doi.org/10.11154/PAIN.33.26","url":null,"abstract":"Objectives. Phantom limb pain is neuropathic pain after amputation of a limb and partial or complete deafferentation such as brachial plexus root avulsion. The underlying cause of this pain has been attributed to maladaptive plasticity of the sensorimotor cortex. It has been suggested that experimental reorganization would affect pain. Here, we tested the hypothesis that a training to use brain–machine interface (BMI) based on magnetoencephalographic (MEG) signals will induce some cortical plasticity in the sensorimotor cortex and modulate the phantom limb pain. Methods. This study included 10 phantom limb patients (9 brachial plexus root avulsion and 1 amputee). MEG signals during movements of the phantom hand or intact hand were used to train the decoder inferring movements of each hand. The robotic hand was controlled by the decoder. Patients controlled the robotic hand by moving the phantom hand. The training effects were compared among trainings with the phantom decoder, real hand decoder, and random decoder in a randomized cross– over trial. Results. BMI training with the phantom decoder increased the decoding accuracy of phantom hand movements and pain. In contrast, BMI training with the intact hand decoder reduced accuracy and pain. Discussion. It was suggested that BMI training to modulate the motor representation of phantom hand controlled pain. The sensorimotor cortical plasticity might induce pain. Symposium 4 : The 39th Annual Meeting of JASP","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"26-31"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.26","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46489152","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}
Crotamiton (N–ethyl–o–crotonotoluidide) has long been used as an anti–itch agent. However, the mechanism by which crotamiton exerts anti–itch effects is unknown. Based on recent studies showing that transient receptor potential (TRP) channels are involved in itch sensations, we hypothesized that crotamiton could affect the activity of TRP channels. In this study, we found that crotamiton strongly inhibits TRPV (vanilloid) 4 channel activity. Crotamiton also inhibited itch–related behaviors induced by the TRPV4–selective agonist GSK1016790A. In patch–clamp experiments we observed large TRPV4 currents following crotamiton washout. In this washout current, single–channel open probabilities and unitary current amplitudes of TRPV4 were increased, which together were suggestive of TRPV4 pore dilation. To explore whether TRPV4 pore dilation occurred, we performed cation replacement experiments in which whole–cell currents and reversal potentials were measured. Our observa tion of increased cation influx and changes in reversal potentials upon crotami ton washout indicated the presence of TRPV4 pore dilation. These results identified TRPV4 as a molecular target of crotamiton and demonstrated pore dilation of TRPV4 upon crotamiton washout.
{"title":"Identification of the molecular target of crotamiton, an anti–itch agent","authors":"Hiroki Kittaka, Y. Yamanoi, M. Tominaga","doi":"10.11154/PAIN.33.47","DOIUrl":"https://doi.org/10.11154/PAIN.33.47","url":null,"abstract":"Crotamiton (N–ethyl–o–crotonotoluidide) has long been used as an anti–itch agent. However, the mechanism by which crotamiton exerts anti–itch effects is unknown. Based on recent studies showing that transient receptor potential (TRP) channels are involved in itch sensations, we hypothesized that crotamiton could affect the activity of TRP channels. In this study, we found that crotamiton strongly inhibits TRPV (vanilloid) 4 channel activity. Crotamiton also inhibited itch–related behaviors induced by the TRPV4–selective agonist GSK1016790A. In patch–clamp experiments we observed large TRPV4 currents following crotamiton washout. In this washout current, single–channel open probabilities and unitary current amplitudes of TRPV4 were increased, which together were suggestive of TRPV4 pore dilation. To explore whether TRPV4 pore dilation occurred, we performed cation replacement experiments in which whole–cell currents and reversal potentials were measured. Our observa tion of increased cation influx and changes in reversal potentials upon crotami ton washout indicated the presence of TRPV4 pore dilation. These results identified TRPV4 as a molecular target of crotamiton and demonstrated pore dilation of TRPV4 upon crotamiton washout.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"47-57"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43488783","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}
Lamina II of the spinal dorsal horn is a major target of nociceptive primary afferents, especially C–fibers and plays a role in modulating and transmitting incoming sensory information. However, its structural and functional organization, and its role in the neuronal circuitry for processing pain information, remain poorly understood due to the difficulty in identifying functional populations among interneurons. Virtually all lamina II neurons are interneurons, and are allocated to inhibitory or excitatory types. Furthermore, these interneurons show morphological, neurochemical and electrophysiological diversity. Thus, it is very important to dissect the local neuronal circuits involving different types of lamina II neurons, in order to understand the output from spinal cord. Recently, we investigated these interneurons by using a combined electrophysiological and anatomical approach. We revealed mechanisms that might con-tribute abnormal pain states through modulation of local circuitry consisting of excitatory and inhibitory interneurons in lamina II. We found a possible local neuronal circuit that might convey signals from low–threshold mechanoreceptors (LTMRs) to lamina I projection neurons through vertical cells (excitatory interneurons). Vertical cells have dendrites spreading ventrally into laminae III ⁄ IV and axons terminating on lamina I projection neurons. We found contacts between dendritic spines of vertical cells and terminals of LTMRs in laminae III ⁄ IV. This circuit is therefore a potential route through which tactile inputs can activate lamina I projection neurons and thus could play a role in tactile allodynia. We also investigated mechanisms to gate these inputs, because this circuit could be inhibited by axo–axonic synapses on the central terminals of LTMRs in normal conditions. It is likely that particular types of lamina II neurons have specific roles in modulating local circuitry, so that the input–output relation could be changed through interactions among different types of interneurons.
{"title":"The cellular and synaptic architecture of local circuits in the spinal dorsal horn","authors":"T. Yasaka","doi":"10.11154/PAIN.33.10","DOIUrl":"https://doi.org/10.11154/PAIN.33.10","url":null,"abstract":"Lamina II of the spinal dorsal horn is a major target of nociceptive primary afferents, especially C–fibers and plays a role in modulating and transmitting incoming sensory information. However, its structural and functional organization, and its role in the neuronal circuitry for processing pain information, remain poorly understood due to the difficulty in identifying functional populations among interneurons. Virtually all lamina II neurons are interneurons, and are allocated to inhibitory or excitatory types. Furthermore, these interneurons show morphological, neurochemical and electrophysiological diversity. Thus, it is very important to dissect the local neuronal circuits involving different types of lamina II neurons, in order to understand the output from spinal cord. Recently, we investigated these interneurons by using a combined electrophysiological and anatomical approach. We revealed mechanisms that might con-tribute abnormal pain states through modulation of local circuitry consisting of excitatory and inhibitory interneurons in lamina II. We found a possible local neuronal circuit that might convey signals from low–threshold mechanoreceptors (LTMRs) to lamina I projection neurons through vertical cells (excitatory interneurons). Vertical cells have dendrites spreading ventrally into laminae III ⁄ IV and axons terminating on lamina I projection neurons. We found contacts between dendritic spines of vertical cells and terminals of LTMRs in laminae III ⁄ IV. This circuit is therefore a potential route through which tactile inputs can activate lamina I projection neurons and thus could play a role in tactile allodynia. We also investigated mechanisms to gate these inputs, because this circuit could be inhibited by axo–axonic synapses on the central terminals of LTMRs in normal conditions. It is likely that particular types of lamina II neurons have specific roles in modulating local circuitry, so that the input–output relation could be changed through interactions among different types of interneurons.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"10-17"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42910943","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}
Fibromyalgia (FM) is characterized by chronic widespread pain with mecha nical allodynia and hyperalgesia. However, the neural mechanisms of nociception and pain are largely unknown. The aim of this study was to examine the responsiveness of peripheral nociceptive afferents and super ficial dorsal horn (SDH) neurons by using a manifest rat model of FM, that was induced by reserpine (RES) injection. Repeated administration of RES ( 1 mg/kg, s.c., once daily for three consecutive days) caused a significant decrease in the mechanical withdrawal threshold of the plantar skin. Single– fiber electrophysiological recordings in vitro revealed that mechanical responses of mechano–responsive C–fibers were increased, although the proportion of mechano–responsive C–nociceptors was paradoxically de -creased. Next, we performed in vivo extracellular recordings of the SDH neurons. Although the SDH neurons showed mechanical stimulus intensity– dependent increases in the discharge rate both in the vehicle (VEH) and the RES–injected group, the response magnitude was significantly greater in the RES–injected group. Some SDH neurons in the RES–injected rats exhibited spontaneous firing with low frequencies, although those in the VEH– injected rats did not. These results suggest that increased mechanical sensitivity of the mechano–responsive C–fibers and the SDH neurons are involved in mechanical allodynia and hyperalgesia in a rat model of RES– induced pain. Similar mechanisms may underlie in patients with FM.
{"title":"Peripheral and spinal mechanisms of nociceptive transmission in a rat model of fibromyalgia","authors":"D. Uta, T. Taguchi","doi":"10.11154/PAIN.32.280","DOIUrl":"https://doi.org/10.11154/PAIN.32.280","url":null,"abstract":"Fibromyalgia (FM) is characterized by chronic widespread pain with mecha nical allodynia and hyperalgesia. However, the neural mechanisms of nociception and pain are largely unknown. The aim of this study was to examine the responsiveness of peripheral nociceptive afferents and super ficial dorsal horn (SDH) neurons by using a manifest rat model of FM, that was induced by reserpine (RES) injection. Repeated administration of RES ( 1 mg/kg, s.c., once daily for three consecutive days) caused a significant decrease in the mechanical withdrawal threshold of the plantar skin. Single– fiber electrophysiological recordings in vitro revealed that mechanical responses of mechano–responsive C–fibers were increased, although the proportion of mechano–responsive C–nociceptors was paradoxically de -creased. Next, we performed in vivo extracellular recordings of the SDH neurons. Although the SDH neurons showed mechanical stimulus intensity– dependent increases in the discharge rate both in the vehicle (VEH) and the RES–injected group, the response magnitude was significantly greater in the RES–injected group. Some SDH neurons in the RES–injected rats exhibited spontaneous firing with low frequencies, although those in the VEH– injected rats did not. These results suggest that increased mechanical sensitivity of the mechano–responsive C–fibers and the SDH neurons are involved in mechanical allodynia and hyperalgesia in a rat model of RES– induced pain. Similar mechanisms may underlie in patients with FM.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"32 1","pages":"280-287"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48622153","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}
Exercise therapy is recommended in the management of patients with chronic pain. However, there is little evidence supporting a relationship between changes in pain or physical disability and changes in physical performance by exercise therapy. Thus, exercise is thought to be involved it directly in the improvement of pain. Exercise has been shown to reduce the peripheral pain sensitivity in healthy subject. This effect, known as exercise– induced hypoalgesia (EIH), may be induced by the activation of central pain modulation systems. However, the effects of acute exercise in chronic pain conditions are heterogeneous and adverse. In patients with chronic pain, for example, exercise seems to decrease pain threshold. Notably, acute exercise followed by physical fatigue induces hyperalgesia. Therefore, regular exercise, rather than acute exercise, is recommended, in the management of patient with chronic pain. Physical inactivity is a perpetuating factor which can cause pain to become chronic. We investigated the relationship between intensity of physical activity in daily life and the function of central pain inhibitory systems. Our results suggested that the function of central pain inhibitory systems may decrease with a low amount of physical activity in women; therefore, maintaining physical activity may be more important for women than for men in preventing chronic pain. The effects and mechanisms of pain inhibition through regular exercise have been suggested using the animal model of pain. According to one of these suggested mechanisms, regular exercise increases the release of met– enkephalin in the rostral ventromedial medulla (RVM) and uses opioid receptors centrally to mediate analgesia. We investigated the influences on central pain inhibitory systems by regular exercise in subjects with chronic pain. While regular exercise for 2 weeks carried out three times a week improved the central pain modulation systems, it was ineffective if only done twice a week. However, an effect was seen if twice–weekly exercise continued for 3 weeks. Therefore, we conclude that increasing physical activity in daily life by regular exercise may be important in prevention and management of chronic pain. Symposium 1 : The 39th Annual Meeting of JASP
{"title":"Influence of exercise on the pain modulation system","authors":"Yukiko Shiro, T. Matsubara","doi":"10.11154/PAIN.32.246","DOIUrl":"https://doi.org/10.11154/PAIN.32.246","url":null,"abstract":"Exercise therapy is recommended in the management of patients with chronic pain. However, there is little evidence supporting a relationship between changes in pain or physical disability and changes in physical performance by exercise therapy. Thus, exercise is thought to be involved it directly in the improvement of pain. Exercise has been shown to reduce the peripheral pain sensitivity in healthy subject. This effect, known as exercise– induced hypoalgesia (EIH), may be induced by the activation of central pain modulation systems. However, the effects of acute exercise in chronic pain conditions are heterogeneous and adverse. In patients with chronic pain, for example, exercise seems to decrease pain threshold. Notably, acute exercise followed by physical fatigue induces hyperalgesia. Therefore, regular exercise, rather than acute exercise, is recommended, in the management of patient with chronic pain. Physical inactivity is a perpetuating factor which can cause pain to become chronic. We investigated the relationship between intensity of physical activity in daily life and the function of central pain inhibitory systems. Our results suggested that the function of central pain inhibitory systems may decrease with a low amount of physical activity in women; therefore, maintaining physical activity may be more important for women than for men in preventing chronic pain. The effects and mechanisms of pain inhibition through regular exercise have been suggested using the animal model of pain. According to one of these suggested mechanisms, regular exercise increases the release of met– enkephalin in the rostral ventromedial medulla (RVM) and uses opioid receptors centrally to mediate analgesia. We investigated the influences on central pain inhibitory systems by regular exercise in subjects with chronic pain. While regular exercise for 2 weeks carried out three times a week improved the central pain modulation systems, it was ineffective if only done twice a week. However, an effect was seen if twice–weekly exercise continued for 3 weeks. Therefore, we conclude that increasing physical activity in daily life by regular exercise may be important in prevention and management of chronic pain. Symposium 1 : The 39th Annual Meeting of JASP","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"32 1","pages":"246-251"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42310756","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}
Irritable bowel syndrome (IBS) is the disease in which abdominal pain and related bowel movements such as diarrhea and constipation persist. IBS is classified in chronic primary pain as well as fibromyalgia and non–specific low back pain. Psychological intervention is important in the treatment of refractory IBS. In particular, cognitive behavioral therapy (CBT) which is a kind of psychotherapy has attracted attention recently. We have developed a Japanese version of the cognitive behavioral therapy protocol for IBS which called CBT–IE and have been practicing on IBS patients. When conducting CBT for patients with chronic pain, including IBS, it is important not to target the disappearance of symptoms, but to aim for improving the quality of life.
{"title":"Cognitive behavioral therapy for irritable bowel syndrome","authors":"Y. Oe, M. Horikoshi","doi":"10.11154/PAIN.32.267","DOIUrl":"https://doi.org/10.11154/PAIN.32.267","url":null,"abstract":"Irritable bowel syndrome (IBS) is the disease in which abdominal pain and related bowel movements such as diarrhea and constipation persist. IBS is classified in chronic primary pain as well as fibromyalgia and non–specific low back pain. Psychological intervention is important in the treatment of refractory IBS. In particular, cognitive behavioral therapy (CBT) which is a kind of psychotherapy has attracted attention recently. We have developed a Japanese version of the cognitive behavioral therapy protocol for IBS which called CBT–IE and have been practicing on IBS patients. When conducting CBT for patients with chronic pain, including IBS, it is important not to target the disappearance of symptoms, but to aim for improving the quality of life.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"32 1","pages":"267-271"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.32.267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47827672","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}
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