Chronic pain is a biological psychosocial pathological condition, which is caused by various elements involved in many ways. Therefore, it is necessary to analyze the disease state from various viewpoints and to treat multimodally. Since there was no standard diagnostic tool for chronic pain so far, it was difficult to develop epidemio-logical research and development and evaluation of treatment in accordance with specific pathological conditions. Therefore, the IASP proceeded development to add the item of Chronic Pain in ICD– 11 , which was officially announced from WHO in June 2018 . This attempts to classify chronic pain into seven major categories ( ① chronic primary pain, ② chronic cancer related pain, ③ chronic postoperative and posttraumatic pain, ④ chronic secondary musculoskeletal pain, ⑤ chronic secondary visceral pain, ⑥ chronic neuropathic pain, ⑦ chronic secondary headache and/or orofacial pain) and others. By developing a more realistic method of using this new standard disease name, effective utilization not only in research but also in clinical practice is needed. In addition, this review will also introduce the versions that the Chronic Pain Research Group of the Ministry of Health, Labor and Welfare has been developing. At the same time as disease name classification, it is important to know where and how to treat chronic pain. , thinking about what kind of patients and where to receive medical treatment.
{"title":"Development of standard classification tool for chronic pain and its clinical application","authors":"T. Ushida, S. Yamaguchi, Y. Kimura, Shuichi Aono","doi":"10.11154/pain.33.257","DOIUrl":"https://doi.org/10.11154/pain.33.257","url":null,"abstract":"Chronic pain is a biological psychosocial pathological condition, which is caused by various elements involved in many ways. Therefore, it is necessary to analyze the disease state from various viewpoints and to treat multimodally. Since there was no standard diagnostic tool for chronic pain so far, it was difficult to develop epidemio-logical research and development and evaluation of treatment in accordance with specific pathological conditions. Therefore, the IASP proceeded development to add the item of Chronic Pain in ICD– 11 , which was officially announced from WHO in June 2018 . This attempts to classify chronic pain into seven major categories ( ① chronic primary pain, ② chronic cancer related pain, ③ chronic postoperative and posttraumatic pain, ④ chronic secondary musculoskeletal pain, ⑤ chronic secondary visceral pain, ⑥ chronic neuropathic pain, ⑦ chronic secondary headache and/or orofacial pain) and others. By developing a more realistic method of using this new standard disease name, effective utilization not only in research but also in clinical practice is needed. In addition, this review will also introduce the versions that the Chronic Pain Research Group of the Ministry of Health, Labor and Welfare has been developing. At the same time as disease name classification, it is important to know where and how to treat chronic pain. , thinking about what kind of patients and where to receive medical treatment.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63527700","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}
This article introduces the recent publication (doi.org/ 10 . 1016 /j.ynpai. 2018 . 07 . 001 ) on the development of new animal model for central post stroke pain ( CPSP ) and its mechanisms through lysophosphatidic acid (LPA) signaling in mice. In this model, the photochemically induced thrombosis (PIT) at middle cerebral artery (MCA) of mouse was made by use of Rose Bengal ( 30 mg/kg, i.v.) and irradiation by green light ( 5 , 000 Lx) for 10 min through the dura mater. Bilateral hyperalgesia in the PIT model was observed when electrical stimulation–induced paw withdrawal (EPW) test using 250 (A δ ) and 2000 Hz (A β ) stimulation was used. As no significant thermal or mecha nical hyperalgesia was observed, we combined the treatment with tissue plasminogen activator (tPA), which was treated at 10 mg/kg (i.v.) 6 h after the start of PIT. Mice treated with tPA and PIT survived and showed stable bilateral hyperalgesia in electrical (EPW), thermal and mechanical nociception tests at least for 18 days without signifi cant behavioral abnormality to make the pain assessment difficult. The hyperalgesia in these tests were completely abolished in mice deficient of LPA 1 and LPA 3 . The systemic treatments of LPA 1 / 3 –receptor antagonist, Ki 16425 at 30 mg/kg (i.p.) twice daily for a week largely abolished the established and bilateral thermal and mecha nical hyperalgesia. Liquid Chromatograph–tandem Mass Spectrometer (LC– MS ⁄ MS) analysis revealed the PIT–induced and tPA–enhanced production of LPA in somato sensory cortex (S–I/II), but not in striatum or ventroposterial thalamus. Interestingly, significant production of LPA in mediodorsal thalamus (MD) was observed by tPA–combined PIT. It remains whether the LPA production in MD is related to the bilateral hyperalgesia in terms of emotional pain pathway. Further analyses of LPA measurements in various brain regions including insular cortex, which has right and left commissure, are highly required.
{"title":"Involvement of lysophosphatidic acid (LPA) in tPA–induced central post stroke pain (CPSP) in mice","authors":"H. Ueda, Ryusei Iwamoto","doi":"10.11154/PAIN.33.269","DOIUrl":"https://doi.org/10.11154/PAIN.33.269","url":null,"abstract":"This article introduces the recent publication (doi.org/ 10 . 1016 /j.ynpai. 2018 . 07 . 001 ) on the development of new animal model for central post stroke pain ( CPSP ) and its mechanisms through lysophosphatidic acid (LPA) signaling in mice. In this model, the photochemically induced thrombosis (PIT) at middle cerebral artery (MCA) of mouse was made by use of Rose Bengal ( 30 mg/kg, i.v.) and irradiation by green light ( 5 , 000 Lx) for 10 min through the dura mater. Bilateral hyperalgesia in the PIT model was observed when electrical stimulation–induced paw withdrawal (EPW) test using 250 (A δ ) and 2000 Hz (A β ) stimulation was used. As no significant thermal or mecha nical hyperalgesia was observed, we combined the treatment with tissue plasminogen activator (tPA), which was treated at 10 mg/kg (i.v.) 6 h after the start of PIT. Mice treated with tPA and PIT survived and showed stable bilateral hyperalgesia in electrical (EPW), thermal and mechanical nociception tests at least for 18 days without signifi cant behavioral abnormality to make the pain assessment difficult. The hyperalgesia in these tests were completely abolished in mice deficient of LPA 1 and LPA 3 . The systemic treatments of LPA 1 / 3 –receptor antagonist, Ki 16425 at 30 mg/kg (i.p.) twice daily for a week largely abolished the established and bilateral thermal and mecha nical hyperalgesia. Liquid Chromatograph–tandem Mass Spectrometer (LC– MS ⁄ MS) analysis revealed the PIT–induced and tPA–enhanced production of LPA in somato sensory cortex (S–I/II), but not in striatum or ventroposterial thalamus. Interestingly, significant production of LPA in mediodorsal thalamus (MD) was observed by tPA–combined PIT. It remains whether the LPA production in MD is related to the bilateral hyperalgesia in terms of emotional pain pathway. Further analyses of LPA measurements in various brain regions including insular cortex, which has right and left commissure, are highly required.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41636361","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}
Itch is defined as an unpleasant sensation that evokes the desire to scratch. Intractable itch and scratching can affect sleep, mood, and personal relationships, signifi cantly reducing quality of life of the chronic pruritic diseases such as atopic derma titis. Pruritogens activate certain receptors on small itch–selective unmyelinated C fibers. Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn. After undergoing processing in the spinal cord, itch signals are conveyed through the spinothalamic tract to the thalamus and through the spinoparabrachial pathway to the parabrachial nucleus. Itch processing activates many brain areas such as the prefrontal cortex (PFC), supplementary motor area (SMA ) , premotor cortex (PM), primary motor cortex (MI), primary somatosensory cortex (SI), parietal cortex, cingulate cortex, precuneus, opercular cortex (OPC) including the secondary somato sensory cortex (SII) and insular cortex (IC), claustrum, basal ganglia including the striatum, thalamus, and cerebellum. Itch was suppressed during and after scratching. It proposed two possible mechanisms by inhibitory circuits of the spinal dorsal horn and descending inhibitory pathway originated from brain such as periaqueductal gray matter (PAG), the raphe nuclei and locus ceruleus. Scratching temporarily relieves itch and can also be rewarding and even addictive. The degree of pleasure obtained by scratching is correlated with itch intensity. In addition, activation of areas of the brain reward system (eg, midbrain and striatum) is observed when an itch is scratched. In the brain, chronic itch modulates activation of particular brain areas, including the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and PFC; alter-nates functional brain connectivity;
{"title":"Brain processing of itch and scratch","authors":"Y. Ishiuji","doi":"10.11154/PAIN.33.315","DOIUrl":"https://doi.org/10.11154/PAIN.33.315","url":null,"abstract":"Itch is defined as an unpleasant sensation that evokes the desire to scratch. Intractable itch and scratching can affect sleep, mood, and personal relationships, signifi cantly reducing quality of life of the chronic pruritic diseases such as atopic derma titis. Pruritogens activate certain receptors on small itch–selective unmyelinated C fibers. Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn. After undergoing processing in the spinal cord, itch signals are conveyed through the spinothalamic tract to the thalamus and through the spinoparabrachial pathway to the parabrachial nucleus. Itch processing activates many brain areas such as the prefrontal cortex (PFC), supplementary motor area (SMA ) , premotor cortex (PM), primary motor cortex (MI), primary somatosensory cortex (SI), parietal cortex, cingulate cortex, precuneus, opercular cortex (OPC) including the secondary somato sensory cortex (SII) and insular cortex (IC), claustrum, basal ganglia including the striatum, thalamus, and cerebellum. Itch was suppressed during and after scratching. It proposed two possible mechanisms by inhibitory circuits of the spinal dorsal horn and descending inhibitory pathway originated from brain such as periaqueductal gray matter (PAG), the raphe nuclei and locus ceruleus. Scratching temporarily relieves itch and can also be rewarding and even addictive. The degree of pleasure obtained by scratching is correlated with itch intensity. In addition, activation of areas of the brain reward system (eg, midbrain and striatum) is observed when an itch is scratched. In the brain, chronic itch modulates activation of particular brain areas, including the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and PFC; alter-nates functional brain connectivity;","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":"43140244","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}
More than 30 years ago, it was found that bombesin originally isolated form frog skin caused scratching ⁄ grooming behaviors in mammals. Subsequently, gastrin– releasing peptide (GRP) and neuromedin B (NMB) were identified as endogenous bombesin family peptides, and those peptides elicited scratching behaviors following intrathecal administration in rodents. After the characterization of GRP receptor (GRPR)–expressing neurons in the spinal dorsal horn in 2007, the understanding of itch transmission has markedly advanced in this 10 years. In both rodents and non human primates, exogenously administered GRP elicits robust scratching behaviors, indicating that activation of GRPR+ neurons is responsible for itch. However, based on several lines of evidence, regulatory mechanisms of GRPR+ neurons are very complicated. A majority of peripherally elicited itch are abolished by ablation of GRPR+ neurons, whereas GRPR antagonist or GRPR–deficiency has limited effects on peri pherally elicited itch. These facts suggest that GRPR+ neurons are activated by not only GRP but also other transmitters such as glutamate. Although there are limited studies for pathological mechanisms of itch, some reports suggest that enhancement of GRP–GRPR system underlies spinal regulation of chronic itch. Given the functional similarities of GRP between rodents and nonhuman primates, it is important to study the detailed mechanisms of GRP–GRPR systems mediating physiological and pathological itch.
{"title":"Spinal GRP mediates itch in nonhuman primates","authors":"Kiguchi Norikazu, Kishioka Shiro, Ko Mei-Chuan","doi":"10.11154/PAIN.33.308","DOIUrl":"https://doi.org/10.11154/PAIN.33.308","url":null,"abstract":"More than 30 years ago, it was found that bombesin originally isolated form frog skin caused scratching ⁄ grooming behaviors in mammals. Subsequently, gastrin– releasing peptide (GRP) and neuromedin B (NMB) were identified as endogenous bombesin family peptides, and those peptides elicited scratching behaviors following intrathecal administration in rodents. After the characterization of GRP receptor (GRPR)–expressing neurons in the spinal dorsal horn in 2007, the understanding of itch transmission has markedly advanced in this 10 years. In both rodents and non human primates, exogenously administered GRP elicits robust scratching behaviors, indicating that activation of GRPR+ neurons is responsible for itch. However, based on several lines of evidence, regulatory mechanisms of GRPR+ neurons are very complicated. A majority of peripherally elicited itch are abolished by ablation of GRPR+ neurons, whereas GRPR antagonist or GRPR–deficiency has limited effects on peri pherally elicited itch. These facts suggest that GRPR+ neurons are activated by not only GRP but also other transmitters such as glutamate. Although there are limited studies for pathological mechanisms of itch, some reports suggest that enhancement of GRP–GRPR system underlies spinal regulation of chronic itch. Given the functional similarities of GRP between rodents and nonhuman primates, it is important to study the detailed mechanisms of GRP–GRPR systems mediating physiological and pathological 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":"45676529","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}
S. Tahara, Hidenori Suzuki, Hironori Izumi, Hidenori Harada, Aki Mori, Fumihiro Higuchi, T. Watanuki, K. Seki, H. Ogasa, T. Taguchi
We organized Yamaguchi Pain Center in Yamaguchi university hospital to treat chronic pain patients. We are performing multidisciplinary therapy and treating the patients in hospital for 3 – 4 weeks. In this study we examined whether there is a differ-ence between elderly and young middle–age suffering from chronic pain. As a result, young middle–aged people were more painful than older people. And Eldelry people did not see psychological improvement of pain. At present it is difficult to change the psychological aspect the pain of elderly people during hospitalization. It is necessary to be able to receive support in the area after other hospital.
{"title":"Interdisaiplinary treatment for chornic pain patients in Yamaguchi Pain Center","authors":"S. Tahara, Hidenori Suzuki, Hironori Izumi, Hidenori Harada, Aki Mori, Fumihiro Higuchi, T. Watanuki, K. Seki, H. Ogasa, T. Taguchi","doi":"10.11154/PAIN.33.220","DOIUrl":"https://doi.org/10.11154/PAIN.33.220","url":null,"abstract":"We organized Yamaguchi Pain Center in Yamaguchi university hospital to treat chronic pain patients. We are performing multidisciplinary therapy and treating the patients in hospital for 3 – 4 weeks. In this study we examined whether there is a differ-ence between elderly and young middle–age suffering from chronic pain. As a result, young middle–aged people were more painful than older people. And Eldelry people did not see psychological improvement of pain. At present it is difficult to change the psychological aspect the pain of elderly people during hospitalization. It is necessary to be able to receive support in the area after other hospital.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49524191","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}
It has been accepted the fact that patients with chronic pain comorbid with depression or anxiety appeal profoundly severe pain condition more than healthful emotional condition. The critical treatment of chronic pain has not been appeared although noradrenergic and serotonergic neurons were discovered as a target of treatment such as depression or anxiety. Recently, the importance of function of the n–3 free fatty acids (FFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid is focused on the novel target of chronic pain. However, the mechanism has not been elucidated. The G–protein coupled receptor 40 ⁄ free fatty acid receptor 1 (GPR40 ⁄ FFAR1), a receptor of middle–long chain FFAs including DHA, distribute in the brain of human and rodents. We previously reported that the GPR40 ⁄ FFAR1 suppressed not only various pain stimuli via activation of endogenous pain regulation systems but also depression–like behavior. Our previous study demonstrated that the GPR40 ⁄ FFAR1 knock–out mice show the persistent of mecha nical allodynia after hind–paw incision. Furthermore, the GPR40 ⁄ FFAR1 knock–out mice show the abnormal emotional behaviors. Our results suggested that the GPR40 ⁄ FFAR1 has the potential of the novel therapeutic target of stress–induced chronic pain.
{"title":"The involvement of GPR40 ⁄ FFAR1 as a novel target of stress induced–chronic pain","authors":"F. Aizawa, K. Nakamoto, S. Tokuyama","doi":"10.11154/PAIN.33.203","DOIUrl":"https://doi.org/10.11154/PAIN.33.203","url":null,"abstract":"It has been accepted the fact that patients with chronic pain comorbid with depression or anxiety appeal profoundly severe pain condition more than healthful emotional condition. The critical treatment of chronic pain has not been appeared although noradrenergic and serotonergic neurons were discovered as a target of treatment such as depression or anxiety. Recently, the importance of function of the n–3 free fatty acids (FFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid is focused on the novel target of chronic pain. However, the mechanism has not been elucidated. The G–protein coupled receptor 40 ⁄ free fatty acid receptor 1 (GPR40 ⁄ FFAR1), a receptor of middle–long chain FFAs including DHA, distribute in the brain of human and rodents. We previously reported that the GPR40 ⁄ FFAR1 suppressed not only various pain stimuli via activation of endogenous pain regulation systems but also depression–like behavior. Our previous study demonstrated that the GPR40 ⁄ FFAR1 knock–out mice show the persistent of mecha nical allodynia after hind–paw incision. Furthermore, the GPR40 ⁄ FFAR1 knock–out mice show the abnormal emotional behaviors. Our results suggested that the GPR40 ⁄ FFAR1 has the potential of the novel therapeutic target of stress–induced chronic pain.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42366331","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. Ushida, K. Noguchi, T. Hosokawa, T. Taguchi, Kazuhisa Takahashi, M. Sumitani, S. Kikuchi
Chronic pain is one of the common health problems among the general popula-tion. Various mechanisms are involved in the pathophysiology of pain, and a correct understanding of its pathophysiology or cause is important for an optimal manage-ment of pain. In terms of the physiological anatomy, pain with physical ⁄ organic causes can be classified mainly as “nociceptive pain” or “neuropathic pain.” However, there is also pain that does not fall into either of these two categories. This type of pain is often considered as a third classification, but its definition has not been standardized globally. In Japan, this type of pain is often called “psychogenic pain,” even when the pain is not attributed to psychological factors. However, it may not be an appropriate term for this particular type of pain. Firstly, because there is no standardized definition, physicians differ in how they classify pain as “psy-chogenic.” Additionally, the term “psychogenic” could give negative impressions to patients, which can deteriorate the patient–physician relationship and may result in poor treatment outcomes. In this paper, we have discussed these problems and proposed a new term “cognitively perceived pain” for this third category of pain, with the aim to foster a more appropriate, and easy–to–understand classification of pain. “Cognitively perceived pain” encompasses all pain that is neither nociceptive nor neuropathic pain, including that described as centralized pain or sensory hypersensitivity, in addition to psychogenic pain according to its original meaning (i.e.
{"title":"Pondering the “psychogenic pain”: Proposal for using the term “cognitively perceived pain”","authors":"T. Ushida, K. Noguchi, T. Hosokawa, T. Taguchi, Kazuhisa Takahashi, M. Sumitani, S. Kikuchi","doi":"10.11154/PAIN.33.183","DOIUrl":"https://doi.org/10.11154/PAIN.33.183","url":null,"abstract":"Chronic pain is one of the common health problems among the general popula-tion. Various mechanisms are involved in the pathophysiology of pain, and a correct understanding of its pathophysiology or cause is important for an optimal manage-ment of pain. In terms of the physiological anatomy, pain with physical ⁄ organic causes can be classified mainly as “nociceptive pain” or “neuropathic pain.” However, there is also pain that does not fall into either of these two categories. This type of pain is often considered as a third classification, but its definition has not been standardized globally. In Japan, this type of pain is often called “psychogenic pain,” even when the pain is not attributed to psychological factors. However, it may not be an appropriate term for this particular type of pain. Firstly, because there is no standardized definition, physicians differ in how they classify pain as “psy-chogenic.” Additionally, the term “psychogenic” could give negative impressions to patients, which can deteriorate the patient–physician relationship and may result in poor treatment outcomes. In this paper, we have discussed these problems and proposed a new term “cognitively perceived pain” for this third category of pain, with the aim to foster a more appropriate, and easy–to–understand classification of pain. “Cognitively perceived pain” encompasses all pain that is neither nociceptive nor neuropathic pain, including that described as centralized pain or sensory hypersensitivity, in addition to psychogenic pain according to its original meaning (i.e.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46749286","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}
There is growing evidence that fatty acids function as signal transduction molecules in a variety of biological phenomena with improved technology and precision of fatty acids analysis. For example, recent study have revealed that the functional properties of fatty acids are modulated by the amount of individual fatty acid intake, identifica-tion of the fatty acid receptors and the changes of its expression, and the distribution of fatty acids among organs. Now, the relationship between polyunsaturated fatty acids and pain is getting a lot of attention as one of the modulation factor of pain. n– 3 fatty acids alleviate pain caused by inflammation and neuropathy, whereas blood levels of n– 6 fatty acids are increased in patients with chronic pain and thus exacerbate pain. Furthermore, we have proposed fatty acid receptors may function as a potential target molecule in pain. On the basis of these reports, it is likely that fatty acids play a major role in the regulation of pain. In this review, we discuss current status and our recent study regarding fatty acids as novel pain management molecules.
{"title":"The role of brain fatty acids in pain","authors":"K. Nakamoto, S. Tokuyama","doi":"10.11154/PAIN.33.193","DOIUrl":"https://doi.org/10.11154/PAIN.33.193","url":null,"abstract":"There is growing evidence that fatty acids function as signal transduction molecules in a variety of biological phenomena with improved technology and precision of fatty acids analysis. For example, recent study have revealed that the functional properties of fatty acids are modulated by the amount of individual fatty acid intake, identifica-tion of the fatty acid receptors and the changes of its expression, and the distribution of fatty acids among organs. Now, the relationship between polyunsaturated fatty acids and pain is getting a lot of attention as one of the modulation factor of pain. n– 3 fatty acids alleviate pain caused by inflammation and neuropathy, whereas blood levels of n– 6 fatty acids are increased in patients with chronic pain and thus exacerbate pain. Furthermore, we have proposed fatty acid receptors may function as a potential target molecule in pain. On the basis of these reports, it is likely that fatty acids play a major role in the regulation of pain. In this review, we discuss current status and our recent study regarding fatty acids as novel pain management molecules.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48483042","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. Kakeda, Kazuko Kaneko, Kouichi Takaoka, Shiho Suzuki–Katayama, Noriyoshi Tanaka, Y. Ogino
Emotional sweating is a physical reaction that occurs with pain and other acutely stressful situations. Very few studies have directly evaluated emotional sweating to monitor pain reception in full–term newborns. The aim of study was to examine whether emotional sweating could applicate for evaluating procedural pain by heel lance in full–term newborns. Eight full–term newborns participated on the fourth day after birth in this study. We examined whether the amount of sweat secretion changed during blood collection procedure. The sweating reaction was recorded continuously from the start of the blood collection until blood collection was finished, using the probe of a portable perspiration meter against the newborn’s palm. As a result, the amount of emotional sweat significantly increased in perspiration accompanied the heel lance, compared to the baseline before blood collection. These finding suggest that emotional sweating could be used as an objective index of procedural pain in full–term newborns.
{"title":"Practical application of emotional sweating to evaluate procedural pain in full–term newborns","authors":"T. Kakeda, Kazuko Kaneko, Kouichi Takaoka, Shiho Suzuki–Katayama, Noriyoshi Tanaka, Y. Ogino","doi":"10.11154/PAIN.33.225","DOIUrl":"https://doi.org/10.11154/PAIN.33.225","url":null,"abstract":"Emotional sweating is a physical reaction that occurs with pain and other acutely stressful situations. Very few studies have directly evaluated emotional sweating to monitor pain reception in full–term newborns. The aim of study was to examine whether emotional sweating could applicate for evaluating procedural pain by heel lance in full–term newborns. Eight full–term newborns participated on the fourth day after birth in this study. We examined whether the amount of sweat secretion changed during blood collection procedure. The sweating reaction was recorded continuously from the start of the blood collection until blood collection was finished, using the probe of a portable perspiration meter against the newborn’s palm. As a result, the amount of emotional sweat significantly increased in perspiration accompanied the heel lance, compared to the baseline before blood collection. These finding suggest that emotional sweating could be used as an objective index of procedural pain in full–term newborns.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47716665","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}
Gangliosides are sialic acid–containing glycosphingolipids that vary greatly in their glyco–chains and are present in biomembranes. Gangliosides are classified into four groups (asialo–, a–, b–, c–series) based on their biosynthetic pathway and on the number of sialic acids present on galactose residues in the second position from the ceramide. Complex gangliosides —gangliosides containing long glycol–chains— are especially abundant in neural tissues, suggesting that they are involved in neural functions such as axonal outgrowth, the preservation of myelin, and neural transmis-sion. We observed that intraplantar injection of GT 1 b ganglioside (b–series complex ganglio side) induces nociceptive behavior, hyperalgesia against 0 . 05 % formalin, and mechanical allodynia. This hyperalgesia is blocked by NMDA receptor antagonists or mGluR 1 antagonists, and is suppressed by co–injection of glutamate dehydrogenase. Furthermore, GT 1 b raises glutamate concentration in skin. These results suggest that hyperalgesia results from the GT 1 b–enhanced elevation of glutamate in skin. This led us to hypothesize that gangliosides modulate pain signaling by regulating glutamate accumulation in skin. Interestingly, a–series gangliosides have no effect on nociceptive behavior. We surmised that this difference that are related to the different positions of sialic acid in a– and b–series gangliosides. Thus, we investigated whether sialidase, an enzyme that removes α –linked sialic acid residues from oligosaccharides, affects nociceptive behavior in a mouse inflammatory pain model produced by intraplantar injec-tions of complete Freund’s adjuvant. Arthrobacter ureafaciens sialidase injection into inflamed paws reduced mechanical allodynia, whereas injection of heat–inactivated enzyme did not. This supports our hypothesis that sialic acid conjugates (e.g., gangliosides) in skin are involved in pain signaling. Although the mechanism by which GT 1 b regulates skin glutamate concentrations remains unclear, it may involve the formation of lipid rafts in membranes. Many studies report that sphingolipids, including ganglio sides, form lipid rafts in membranes that regulate protein–protein interactions, which in turn produce changes in intracellular signal transduction, protein localiza-tion, and vesicular transport. Future studies are required to clarify how gangliosides regulate glutamate concentration via the lipid raft theory. Gangliosides might receive more attention in the future as potential therapeutic targets for pain management, because of their relationship with pain signaling.
神经节苷是一种含唾液酸的鞘糖脂，其糖链变化很大，存在于生物膜中。根据它们的生物合成途径和在神经酰胺的第二位置的半乳糖残基上存在的唾液酸的数量，神经节苷类被分为四类(asialo -， a -， b -， c系列)。复杂神经节苷——含有长乙二醇链的神经节苷——在神经组织中尤其丰富，这表明它们参与神经功能，如轴突生长、髓磷脂的保存和神经传递。我们观察到足底注射gt1 b神经节苷脂(b系列复杂神经节侧)诱导伤害性行为，痛觉过敏对0。05%福尔马林和机械异常性疼痛。这种痛觉过敏可被NMDA受体拮抗剂或mGluR - 1拮抗剂阻断，并通过谷氨酸脱氢酶联合注射抑制。此外，gb1可提高皮肤中的谷氨酸浓度。这些结果表明，痛觉过敏是由皮肤中谷氨酸升高引起的。这导致我们假设神经节苷通过调节皮肤中的谷氨酸积累来调节疼痛信号。有趣的是，a系列神经节苷脂对伤害性行为没有影响。我们推测这种差异与唾液酸在a系列和b系列神经节苷中的不同位置有关。因此，我们研究了唾液酸酶(一种从寡糖中去除α -连接唾液酸残基的酶)是否会影响足底注射完全弗氏佐剂产生的小鼠炎症性疼痛模型中的伤害性行为。关节杆菌唾液酸酶注射到发炎的爪子减少机械异常性痛，而注射热灭活酶没有。这支持了我们的假设，即皮肤中的唾液酸偶联物(如神经节苷脂)与疼痛信号有关。虽然gb1调节皮肤谷氨酸浓度的机制尚不清楚，但它可能与膜中脂筏的形成有关。许多研究报道鞘脂，包括神经节侧，在膜上形成脂筏，调节蛋白-蛋白相互作用，进而产生细胞内信号转导、蛋白定位和囊泡运输的变化。未来的研究需要阐明神经节苷如何通过脂质筏理论调节谷氨酸浓度。由于神经节苷类与疼痛信号的关系，它们可能会在未来作为疼痛管理的潜在治疗靶点受到更多的关注。
{"title":"Sialic acid–containing glycosphingolipids: functional roles of gangliosides in pain signaling","authors":"Shun Watanabe, M. Tanabe","doi":"10.11154/PAIN.33.32","DOIUrl":"https://doi.org/10.11154/PAIN.33.32","url":null,"abstract":"Gangliosides are sialic acid–containing glycosphingolipids that vary greatly in their glyco–chains and are present in biomembranes. Gangliosides are classified into four groups (asialo–, a–, b–, c–series) based on their biosynthetic pathway and on the number of sialic acids present on galactose residues in the second position from the ceramide. Complex gangliosides —gangliosides containing long glycol–chains— are especially abundant in neural tissues, suggesting that they are involved in neural functions such as axonal outgrowth, the preservation of myelin, and neural transmis-sion. We observed that intraplantar injection of GT 1 b ganglioside (b–series complex ganglio side) induces nociceptive behavior, hyperalgesia against 0 . 05 % formalin, and mechanical allodynia. This hyperalgesia is blocked by NMDA receptor antagonists or mGluR 1 antagonists, and is suppressed by co–injection of glutamate dehydrogenase. Furthermore, GT 1 b raises glutamate concentration in skin. These results suggest that hyperalgesia results from the GT 1 b–enhanced elevation of glutamate in skin. This led us to hypothesize that gangliosides modulate pain signaling by regulating glutamate accumulation in skin. Interestingly, a–series gangliosides have no effect on nociceptive behavior. We surmised that this difference that are related to the different positions of sialic acid in a– and b–series gangliosides. Thus, we investigated whether sialidase, an enzyme that removes α –linked sialic acid residues from oligosaccharides, affects nociceptive behavior in a mouse inflammatory pain model produced by intraplantar injec-tions of complete Freund’s adjuvant. Arthrobacter ureafaciens sialidase injection into inflamed paws reduced mechanical allodynia, whereas injection of heat–inactivated enzyme did not. This supports our hypothesis that sialic acid conjugates (e.g., gangliosides) in skin are involved in pain signaling. Although the mechanism by which GT 1 b regulates skin glutamate concentrations remains unclear, it may involve the formation of lipid rafts in membranes. Many studies report that sphingolipids, including ganglio sides, form lipid rafts in membranes that regulate protein–protein interactions, which in turn produce changes in intracellular signal transduction, protein localiza-tion, and vesicular transport. Future studies are required to clarify how gangliosides regulate glutamate concentration via the lipid raft theory. Gangliosides might receive more attention in the future as potential therapeutic targets for pain management, because of their relationship with pain signaling.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":"33 1","pages":"32-39"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/PAIN.33.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44835405","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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