Many of analgesics and analgesic adjuvants act on nerve conduction and synaptic transmission in the nervous system to inhibit nociceptive transmission. It has not been fully examined how nerve conduction inhibition leading to antinociception differs in extent among various analgesics and analgesic adjuvants. We examined quantitatively their actions on fast–conducting compound action potentials (CAPs) recorded from the frog sciatic nerve. Drugs tested were local anesthetics, opioids, adrenoceptor agonists, antiepileptics, antidepressants and non–steroidal anti– inflam matory drugs (NSAIDs). As a result, we found that many of their drugs reduce the peak amplitude of the CAPs in a manner dependent on their chemical structures. Consistent with voltage–gated Na + –channel inhibition produced by local anesthetics, CAP peak amplitudes were reduced by procaine, cocaine, tetracaine, prilocaine, lidocaine, ropivacaine, levobupivacaine and pramoxine with the half– maximal inhibitory concentration (IC 50 ) values of 2 . 2 , 0 . 80 , 0 . 013 , 1 . 8 , 0 . 74 , 0 . 34 , 0 . 23 and 0 . 21 mM, respectively. A weak opioid tramadol reduced CAP peak amplitude s (IC 50 = 2 . 3 mM) more effectively than its metabolite mono– O – demethyl–tramadol; this distinction was attributed to such a difference in chemical structure that tramadol and mono– O –demethyl–tramadol have –OCH 3 and –OH bound to a benzene ring, respectively. Moreover, NSAIDs [tolfenamic acid, meclofenamic acid and flufenamic acid (IC 50 values: 0 . 29 , 0 . 19 and 0 . 22 mM, respectively)]. On the other hand, salicylic acid–based (aspirin), propionic acid–based (ketoprofen, ibuprofen, naproxen, loxoprofen and flurbiprofen) and enolic acid–based (meloxicam and piroxicam) NSAIDs had no effect on CAPs. In conclusion, CAP inhibitions produced by local anesthetics were partly comparable in extent to those of a 2 –adrenoceptor agonists, antiepileptics, antidepressants and NSAIDs; opioids inhibited CAPs less potently than their drugs. It is suggested that analgesics and analgesic adjuvants inhibit nerve conduction in a manner dependent on their chemical structures.
许多镇痛药和镇痛佐剂作用于神经系统的神经传导和突触传递，抑制伤害性传递。神经传导抑制导致的抗痛觉作用在不同镇痛药和镇痛佐剂之间的程度如何不同还没有得到充分的研究。我们定量地检测了它们对青蛙坐骨神经记录的快速传导复合动作电位(CAPs)的作用。测试的药物包括局麻药、阿片类药物、肾上腺素受体激动剂、抗癫痫药、抗抑郁药和非甾体抗炎药(NSAIDs)。结果，我们发现他们的许多药物以一种依赖于其化学结构的方式降低了cap的峰值幅度。普鲁卡因、可卡因、丁卡因、普丙卡因、利多卡因、罗哌卡因、左旋布比卡因和普拉莫辛均可降低CAP峰幅，半数最大抑制浓度(IC 50)为2，与局麻药产生的电压门控Na +通道抑制一致。2,0。80,0。[13, 1]8,0。74,0。34,0。23和0。分别为21毫米。弱阿片类药物曲马多降低了CAP峰振幅s (ic50 = 2)。3 mM)比其代谢物单O -去甲基曲马多更有效;这种区别是由于曲马多和单- O -去甲基曲马多在化学结构上的差异，它们的苯环上分别有- och 3和- oh键。非甾体抗炎药[甲氯芬那酸、甲氯芬那酸和氟芬那酸]的ic50值为0。29,0。19和0。22 mM)]。另一方面，水杨酸类非甾体抗炎药(阿司匹林)、丙酸类非甾体抗炎药(酮洛芬、布洛芬、萘普生、洛洛芬和氟比洛芬)和烯酸类非甾体抗炎药(美洛昔康和吡洛昔康)对CAPs无影响。综上所述，局麻药对CAP的抑制作用在一定程度上与a - 2肾上腺素受体激动剂、抗癫痫药、抗抑郁药和非甾体抗炎药相当;阿片类药物对cap的抑制作用不如药物。这表明，镇痛药和镇痛佐剂抑制神经传导的方式依赖于它们的化学结构。
{"title":"Analgesics and analgesic adjuvants inhibiting nerve conduction in the frog sciatic nerve —local anesthetics, opioids, α2 adrenoceptor agonists, antiepileptics, antidepressants and NSAIDs","authors":"E. Kumamoto, T. Fujita","doi":"10.11154/pain.34.291","DOIUrl":"https://doi.org/10.11154/pain.34.291","url":null,"abstract":"Many of analgesics and analgesic adjuvants act on nerve conduction and synaptic transmission in the nervous system to inhibit nociceptive transmission. It has not been fully examined how nerve conduction inhibition leading to antinociception differs in extent among various analgesics and analgesic adjuvants. We examined quantitatively their actions on fast–conducting compound action potentials (CAPs) recorded from the frog sciatic nerve. Drugs tested were local anesthetics, opioids, adrenoceptor agonists, antiepileptics, antidepressants and non–steroidal anti– inflam matory drugs (NSAIDs). As a result, we found that many of their drugs reduce the peak amplitude of the CAPs in a manner dependent on their chemical structures. Consistent with voltage–gated Na + –channel inhibition produced by local anesthetics, CAP peak amplitudes were reduced by procaine, cocaine, tetracaine, prilocaine, lidocaine, ropivacaine, levobupivacaine and pramoxine with the half– maximal inhibitory concentration (IC 50 ) values of 2 . 2 , 0 . 80 , 0 . 013 , 1 . 8 , 0 . 74 , 0 . 34 , 0 . 23 and 0 . 21 mM, respectively. A weak opioid tramadol reduced CAP peak amplitude s (IC 50 = 2 . 3 mM) more effectively than its metabolite mono– O – demethyl–tramadol; this distinction was attributed to such a difference in chemical structure that tramadol and mono– O –demethyl–tramadol have –OCH 3 and –OH bound to a benzene ring, respectively. Moreover, NSAIDs [tolfenamic acid, meclofenamic acid and flufenamic acid (IC 50 values: 0 . 29 , 0 . 19 and 0 . 22 mM, respectively)]. On the other hand, salicylic acid–based (aspirin), propionic acid–based (ketoprofen, ibuprofen, naproxen, loxoprofen and flurbiprofen) and enolic acid–based (meloxicam and piroxicam) NSAIDs had no effect on CAPs. In conclusion, CAP inhibitions produced by local anesthetics were partly comparable in extent to those of a 2 –adrenoceptor agonists, antiepileptics, antidepressants and NSAIDs; opioids inhibited CAPs less potently than their drugs. It is suggested that analgesics and analgesic adjuvants inhibit nerve conduction in a manner dependent on their chemical structures.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48547942","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}
Chronic pain is known to get worse under the influence of weather change (tempera -ture, humidity, pressure). This is generally called “weather–related pain”. The author believes that the pressure sensor in the inner ear and the autonomic nervous system imbalance are involved in the mechanism of worsening pain and associated symptoms due to a decrease in atmospheric pressure. In addition, the activation mechanism of the cold receptor on skin occurs in chronic pain, which is considered to be the main role of the mechanism of aggravation of chronic pain under low tem perature environments.
{"title":"Mechanism of weather–related pain","authors":"J. Sato","doi":"10.11154/pain.34.312","DOIUrl":"https://doi.org/10.11154/pain.34.312","url":null,"abstract":"Chronic pain is known to get worse under the influence of weather change (tempera -ture, humidity, pressure). This is generally called “weather–related pain”. The author believes that the pressure sensor in the inner ear and the autonomic nervous system imbalance are involved in the mechanism of worsening pain and associated symptoms due to a decrease in atmospheric pressure. In addition, the activation mechanism of the cold receptor on skin occurs in chronic pain, which is considered to be the main role of the mechanism of aggravation of chronic pain under low tem perature environments.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47811820","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 much evidence showing that a group of neuropeptides produced in the hypo thalamus, oxytocin and orexins, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to reveal cellular mechanisms underlying this antinociception, we examined how oxytocin, orexins A and B affect spontaneous synaptic transmission in rat spinal lamina II (substantia gelatinosa; SG) neurons, which play a pivotal role in regulating nociceptive transmission. The experiments were performed by applying the blind whole–cell patch–clamp technique to SG neurons in adult rat spinal cord slices. Bath–applied oxytocin unaffected glutamatergic spontaneous excitatory transmission while producing an inward current at − 70 mV (membrane depolarization) and enhancing both GABAergic and glycinergic spontaneous inhibitory transmissions in > 70 % of the neurons tested. The depolarization, and increased GABAergic and glycinergic spontaneous inhibitory postsynaptic current (sIPSC) frequencies were concentration–dependent with half–maximal effective concentration (EC 50 ) values of 0 . 022 , 0 . 024 and 0 . 038 µM, respectively. On the other hand, orexins A and B produced an inward current at − 70 mV and/or increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude in some 70 % of the neurons examined. EC 50 values for orexin A in their effects were 0 . 0045 and 0 . 030 µM, respectively; those for orexin B were 0 . 020 and 0 . 039 µM, respectively. EC 50 value for orexin B in producing inward current was similar to that of oxytocin nist (SB 334867 ) but not an orexin– 2 receptor antagonist (JNJ 10397049 ) while orexin B activities were inhibited by JNJ 10397049 but not SB 334867 , indicating that orexins A and B activities are mediated by orexin– 1 and – 2 receptors, respectively. It is concluded that oxytocin, orexins A and B increase neuronal activity through membrane depolari zation and/or increased L –glutamate release from nerve terminals, by activating their specific receptors, which in turn results in GABAergic and/or glycinergic spontaneous inhibitory transmission enhancements, a possible mechanism for antinociception.
{"title":"Cellular mechanisms for antinociception produced by hypothalamus–derived neuropeptides in the rat spinal superficial dorsal horn —oxytocin and orexins actions","authors":"E. Kumamoto, T. Fujita, Chong Wang","doi":"10.11154/pain.34.228","DOIUrl":"https://doi.org/10.11154/pain.34.228","url":null,"abstract":"There is much evidence showing that a group of neuropeptides produced in the hypo thalamus, oxytocin and orexins, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to reveal cellular mechanisms underlying this antinociception, we examined how oxytocin, orexins A and B affect spontaneous synaptic transmission in rat spinal lamina II (substantia gelatinosa; SG) neurons, which play a pivotal role in regulating nociceptive transmission. The experiments were performed by applying the blind whole–cell patch–clamp technique to SG neurons in adult rat spinal cord slices. Bath–applied oxytocin unaffected glutamatergic spontaneous excitatory transmission while producing an inward current at − 70 mV (membrane depolarization) and enhancing both GABAergic and glycinergic spontaneous inhibitory transmissions in > 70 % of the neurons tested. The depolarization, and increased GABAergic and glycinergic spontaneous inhibitory postsynaptic current (sIPSC) frequencies were concentration–dependent with half–maximal effective concentration (EC 50 ) values of 0 . 022 , 0 . 024 and 0 . 038 µM, respectively. On the other hand, orexins A and B produced an inward current at − 70 mV and/or increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude in some 70 % of the neurons examined. EC 50 values for orexin A in their effects were 0 . 0045 and 0 . 030 µM, respectively; those for orexin B were 0 . 020 and 0 . 039 µM, respectively. EC 50 value for orexin B in producing inward current was similar to that of oxytocin nist (SB 334867 ) but not an orexin– 2 receptor antagonist (JNJ 10397049 ) while orexin B activities were inhibited by JNJ 10397049 but not SB 334867 , indicating that orexins A and B activities are mediated by orexin– 1 and – 2 receptors, respectively. It is concluded that oxytocin, orexins A and B increase neuronal activity through membrane depolari zation and/or increased L –glutamate release from nerve terminals, by activating their specific receptors, which in turn results in GABAergic and/or glycinergic spontaneous inhibitory transmission enhancements, a possible mechanism for antinociception.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49385534","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}
Shiori Kawasaki, M. Fujita, Isamu Nanchi, Sunao Imai, Yasuhide Morioka, T. Asaki
Interstitial cystitis ⁄ painful bladder syndrome (IC ⁄ PBS) is a chronic bladder disorder accompanied by urinary dysfunction and bladder pain. The bladder pain is often resistant to current analgesics, such as amitriptyline and gabapentin, and decreases the quality of life for patients with IC ⁄ PBS. Novel analgesics with greater efficacy are urgently required; however, the pain mechanism in IC ⁄ PBS is not fully understood. Transient receptor potential vanilloid– 4 (TRPV 4 ) is expressed in the bladder epithelium to detect the mechanical stimulation associated with cell swelling and shear stress. Some reports have shown the involvement of TRPV 4 in urinary dysfunction in rodent models, but little is known about bladder pain. Therefore, we investigated whether TRPV 4 could be involved in the bladder pain induced by cyclophosphamide (CYP) in mice. Repeated intraperitoneal injection of CYP at 150 mg/kg for 4 days produced mild edema with some infiltration of inflammatory cells in the bladder, and persist ent mechanical hypersensitivity in the lower abdomen of mice. The phosphorylated TRPV 4 was significantly increased in the bladder of chronic cystitis mice, although the level of TRPV 4 mRNA and the distribution of TRPV 4 were not changed in the bladder compared with vehicle–injected mice. The gene depletion of TRPV 4 com-pletely prevented mechanical hypersensitivity in chronic cystitis mice. In addition, oral administration of the TRPV 4 antagonist, GSK 2193874 , inhibited mecha nical hyper sensitivity in these mice. These results show that the TRPV 4 antagonis t may become a therapeutic option for bladder pain in patients with IC ⁄ PBS.
{"title":"Analgesic effect of TRPV4 blockade on bladder pain in chronic cystitis mice","authors":"Shiori Kawasaki, M. Fujita, Isamu Nanchi, Sunao Imai, Yasuhide Morioka, T. Asaki","doi":"10.11154/pain.34.240","DOIUrl":"https://doi.org/10.11154/pain.34.240","url":null,"abstract":"Interstitial cystitis ⁄ painful bladder syndrome (IC ⁄ PBS) is a chronic bladder disorder accompanied by urinary dysfunction and bladder pain. The bladder pain is often resistant to current analgesics, such as amitriptyline and gabapentin, and decreases the quality of life for patients with IC ⁄ PBS. Novel analgesics with greater efficacy are urgently required; however, the pain mechanism in IC ⁄ PBS is not fully understood. Transient receptor potential vanilloid– 4 (TRPV 4 ) is expressed in the bladder epithelium to detect the mechanical stimulation associated with cell swelling and shear stress. Some reports have shown the involvement of TRPV 4 in urinary dysfunction in rodent models, but little is known about bladder pain. Therefore, we investigated whether TRPV 4 could be involved in the bladder pain induced by cyclophosphamide (CYP) in mice. Repeated intraperitoneal injection of CYP at 150 mg/kg for 4 days produced mild edema with some infiltration of inflammatory cells in the bladder, and persist ent mechanical hypersensitivity in the lower abdomen of mice. The phosphorylated TRPV 4 was significantly increased in the bladder of chronic cystitis mice, although the level of TRPV 4 mRNA and the distribution of TRPV 4 were not changed in the bladder compared with vehicle–injected mice. The gene depletion of TRPV 4 com-pletely prevented mechanical hypersensitivity in chronic cystitis mice. In addition, oral administration of the TRPV 4 antagonist, GSK 2193874 , inhibited mecha nical hyper sensitivity in these mice. These results show that the TRPV 4 antagonis t may become a therapeutic option for bladder pain in patients with IC ⁄ PBS.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45801374","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, K. Nakai, H. Kato, J. Hatazawa, Y. Yoshioka, T. Yanagida
Introduction: In our clinical situation, pain is evaluated by the subjective complaints reported by patients because an objective measurement is still unrealizable. As an alter native, we usually evaluate pain–related behaviour to analyze animal pain. However, the phenomenon of analyzing pain–related behaviour is limited because some amounts of stimulations are required to be provided first. At present, the opinion that pain–related behaviour is not a response to pain but a mere reflex still cannot be completely disproved. Moreover, as observed with chronic pain patients, pain triggered by some kind of stimuli is less important than pain experienced continuous ly in a given period from our group’s clinical data. This means that the common pain study using the general way of evaluation cannot contribute to new analgesics’ discovery which patients are eager to await. The goal of this study is to evaluate rodents’ spontaneous pain objectively without any stimulation by high resolutio n MRI. Methods: All surgical and experimental protocols were approved by the Institutional Animal Care and Use Committee of Osaka university graduate school of medicine. 31 male Wister rats were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and sevoflurane (2 – 3%). An infra–orbital nerve (ION) loose ligation model was made by the procedure that two nylon (5–0) ligatures (2 mm apart) were loosely tied around the ION. Sham–operation was performed only by cutting the skin on the face and suturing in the same way as the procedure of ION loose ligation model. The scanning schedule was set 3 weeks after surgery and 3 days before the scanning day, 5 mg/kg manganese was injected intraperitoneally for three days. MRI measurements were performed with an 11.7 T MR scanner (AVANCE 500WB, Bruker BioSpin MRI GmbH, Ettlingen, Germany), under isoflurane anesthesia (2 – 2.5%), T1 weighted MR–images were acquired with a spin echo sequence. All the images were standardized and divided into 52 areas automatically and uptakes of manganese were analyzed. Tukey–Kramer multiple comparison test and correlation analyses were performed using JMP12.0.0 software.
{"title":"Evaluation of spontaneous oro–facial neuropathic pain in animal model using high resolution MRI","authors":"A. Nakae, K. Nakai, H. Kato, J. Hatazawa, Y. Yoshioka, T. Yanagida","doi":"10.11154/pain.34.254","DOIUrl":"https://doi.org/10.11154/pain.34.254","url":null,"abstract":"Introduction: In our clinical situation, pain is evaluated by the subjective complaints reported by patients because an objective measurement is still unrealizable. As an alter native, we usually evaluate pain–related behaviour to analyze animal pain. However, the phenomenon of analyzing pain–related behaviour is limited because some amounts of stimulations are required to be provided first. At present, the opinion that pain–related behaviour is not a response to pain but a mere reflex still cannot be completely disproved. Moreover, as observed with chronic pain patients, pain triggered by some kind of stimuli is less important than pain experienced continuous ly in a given period from our group’s clinical data. This means that the common pain study using the general way of evaluation cannot contribute to new analgesics’ discovery which patients are eager to await. The goal of this study is to evaluate rodents’ spontaneous pain objectively without any stimulation by high resolutio n MRI. Methods: All surgical and experimental protocols were approved by the Institutional Animal Care and Use Committee of Osaka university graduate school of medicine. 31 male Wister rats were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and sevoflurane (2 – 3%). An infra–orbital nerve (ION) loose ligation model was made by the procedure that two nylon (5–0) ligatures (2 mm apart) were loosely tied around the ION. Sham–operation was performed only by cutting the skin on the face and suturing in the same way as the procedure of ION loose ligation model. The scanning schedule was set 3 weeks after surgery and 3 days before the scanning day, 5 mg/kg manganese was injected intraperitoneally for three days. MRI measurements were performed with an 11.7 T MR scanner (AVANCE 500WB, Bruker BioSpin MRI GmbH, Ettlingen, Germany), under isoflurane anesthesia (2 – 2.5%), T1 weighted MR–images were acquired with a spin echo sequence. All the images were standardized and divided into 52 areas automatically and uptakes of manganese were analyzed. Tukey–Kramer multiple comparison test and correlation analyses were performed using JMP12.0.0 software.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49090783","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}
Non–coding RNAs affect various cellular processes through interaction with DNA, RNA and protein. Accordingly, non–coding RNAs, microRNAs and more recently long non–coding RNAs, have been shown to be involved in pain disorders, including neuropathic pain. MicroRNAs inhibit translational step of gene expression and dysregulation of microRNAs underlies the neuropathic pain. On the other hand, lncRNAs regulate diverse steps of gene expression, including epigenetic modulation, transcription, alternative splicing and translation, although a role of lncRNAs in the pain disorders remain poorly understood. Interestingly, a part of non–coding RNAs are released to extracellular space and mediate a cell–cell communication. Extracellular microRNAs are shown to modulate nociceptive transmission. Furthermore, extracellular non–coding RNAs are expected as a specific biomarker for neuronal damage or pain in the blood. In this review, we summarize current insights into non–coding RNA significance in the neuropathic pain.
{"title":"MicroRNA and long non–coding RNA in neuropathic pain","authors":"A. Sakai, Motoyo Maruyama, Hidenori Suzuki","doi":"10.11154/pain.34.219","DOIUrl":"https://doi.org/10.11154/pain.34.219","url":null,"abstract":"Non–coding RNAs affect various cellular processes through interaction with DNA, RNA and protein. Accordingly, non–coding RNAs, microRNAs and more recently long non–coding RNAs, have been shown to be involved in pain disorders, including neuropathic pain. MicroRNAs inhibit translational step of gene expression and dysregulation of microRNAs underlies the neuropathic pain. On the other hand, lncRNAs regulate diverse steps of gene expression, including epigenetic modulation, transcription, alternative splicing and translation, although a role of lncRNAs in the pain disorders remain poorly understood. Interestingly, a part of non–coding RNAs are released to extracellular space and mediate a cell–cell communication. Extracellular microRNAs are shown to modulate nociceptive transmission. Furthermore, extracellular non–coding RNAs are expected as a specific biomarker for neuronal damage or pain in the blood. In this review, we summarize current insights into non–coding RNA significance in the neuropathic pain.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49176791","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}
W. Taniguchi, N. Nishio, Manabu Yamanaka, R. Taiji, S. Tsutsui, T. Nakatsuka, H. Yamada
Osteoarthritis of the knee (knee OA) is a common disease in the elderly, and the chief complaint of these patients is knee pain. Knee OA pain reduces the activities of daily living and the quality of life in these patients. The degree of pain does not correlate with radiographic grades, and the intense wear of the cartilage does not neces sarily mean intense pain. However, the cellular mechanism of chronic pain in this disease has been unclear. This study aimed to investigate the effects of the transient receptor potential vanilloid 1 (TRPV 1 ) on weight–bearing pain–related behaviors in knee OA model rats using the CatWalk system. To generate the knee OA model, monosodium iodoacetate (MIA) was injected in the right knee joint of male adult Sprague–Dawley rats. Four weeks after the MIA injection, we used the knee OA rats for the behavioral study. Using the CatWalk system, we investigated the effects of the intra–articular injection of the TRPV 1 selective agonist capsaicin, TRPV 1 selective antagonist capsazepine, and saline on the nociceptive behaviors of the rats with knee OA at 1 , 2 , 7 , and 10 days after the intra–articular injection. The rats treated with intra–articular capsazepine injection showed significantly greater improvement in swing speed, a pain–related behavioral parameter of the CatWalk system, than those treated with capsaicin on day 2 after injection. The maximum contact area on day 10 showed significantly greater improvement in the capsazepine group than in the capsaicin group. These results suggest that TRPV 1 is an important contributor to weight–bearing pain–related behavior of patients with knee OA. However, in this study, these effects were observed at later time points. Thus, TRPV 1 could be related to not only the peripheral nociceptive pain mechanism, but also to the secondary pain mechanism.
{"title":"Analysis of the relationship between knee osteoarthritis weight–bearing pain and transient receptor potential vanilloid 1 using the CatWalk system","authors":"W. Taniguchi, N. Nishio, Manabu Yamanaka, R. Taiji, S. Tsutsui, T. Nakatsuka, H. Yamada","doi":"10.11154/pain.34.247","DOIUrl":"https://doi.org/10.11154/pain.34.247","url":null,"abstract":"Osteoarthritis of the knee (knee OA) is a common disease in the elderly, and the chief complaint of these patients is knee pain. Knee OA pain reduces the activities of daily living and the quality of life in these patients. The degree of pain does not correlate with radiographic grades, and the intense wear of the cartilage does not neces sarily mean intense pain. However, the cellular mechanism of chronic pain in this disease has been unclear. This study aimed to investigate the effects of the transient receptor potential vanilloid 1 (TRPV 1 ) on weight–bearing pain–related behaviors in knee OA model rats using the CatWalk system. To generate the knee OA model, monosodium iodoacetate (MIA) was injected in the right knee joint of male adult Sprague–Dawley rats. Four weeks after the MIA injection, we used the knee OA rats for the behavioral study. Using the CatWalk system, we investigated the effects of the intra–articular injection of the TRPV 1 selective agonist capsaicin, TRPV 1 selective antagonist capsazepine, and saline on the nociceptive behaviors of the rats with knee OA at 1 , 2 , 7 , and 10 days after the intra–articular injection. The rats treated with intra–articular capsazepine injection showed significantly greater improvement in swing speed, a pain–related behavioral parameter of the CatWalk system, than those treated with capsaicin on day 2 after injection. The maximum contact area on day 10 showed significantly greater improvement in the capsazepine group than in the capsaicin group. These results suggest that TRPV 1 is an important contributor to weight–bearing pain–related behavior of patients with knee OA. However, in this study, these effects were observed at later time points. Thus, TRPV 1 could be related to not only the peripheral nociceptive pain mechanism, but also to the secondary pain mechanism.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11154/pain.34.247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44823474","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}
Multidisciplinary pain management is one of the useful methods for the treatment of chronic musculoskeletal pain, as has been demonstrated in the USA since 1950s. A biopsychosocial model of well–being is a very important concept in the multidisciplinary treatment. This model is a general model or approach stating that biological, psycho logical, and social factors play a significant role in human functioning in the context of disease or illness. Currently there are few facilities in Japan that administer a multidisciplinary pain treatment, especially an inpatient pain management program. We are implementing a multidisciplinary pain management program based on biopsychosocial model guided by the IASP recommendations for such a program in Fukushima, Japan. The purpose of this study was to describe our initial efforts in creating a Japanese inpatient pain management program using the biopsychosocial method of self–pain management. The pain management center was started in April 2015 with a team consisting of ortho paedic surgeons, psychiatrists, nurses, physical therapists, clinical psychologists, pharmacists, and nutritionists. Our 3–week inpatient pain management program is indicated for patients who find it hard to work or go to school due to chronic musculoskeletal pain, and/or are confined to life at home but want to return to work or school. This program consists of exercise therapy, psychotherapy, and cognitive behavior al therapy. Using this program, our inpatients with intractable chronic muscu loskeletal pain were evaluated using brief pain inventory (BPI), pain catastrophizing scale (PCS) (rumination, magnification, and helplessness), pain disability assessment scale (PDAS), hospital anxiety and depression scale (HADS), pain self– efficacy questionnaire (PSEQ), EQ–5D, and physical functions (flexibility, muscle endurance, walking ability, and physical fitness). Statistical analyses were performed using the paired t–test and Wilcoxon matched pairs signed rank sum test with Bonferroni correction after Friedman test. Twenty–one patients (7 male and 14 female; 20–79 years old (Average 52.2 years old)) were analyzed from April 2015 to December 2017. Comparing results before and after the program, the following statistically significant improvement were seen in BPI, PCS (rumination, magnification, helplessness), PDAS, HADS anxiety and depression scale, PSEQ, EQ–5D, 30–sec sit to stand test (muscle endurance), 2 step test (walking ability), and 6–minute walking test
{"title":"Multidisciplinary inpatient pain management program for chronic musculoskeletal pain","authors":"N. Takahashi, S. Kasahara, S. Yabuki","doi":"10.11154/PAIN.34.44","DOIUrl":"https://doi.org/10.11154/PAIN.34.44","url":null,"abstract":"Multidisciplinary pain management is one of the useful methods for the treatment of chronic musculoskeletal pain, as has been demonstrated in the USA since 1950s. A biopsychosocial model of well–being is a very important concept in the multidisciplinary treatment. This model is a general model or approach stating that biological, psycho logical, and social factors play a significant role in human functioning in the context of disease or illness. Currently there are few facilities in Japan that administer a multidisciplinary pain treatment, especially an inpatient pain management program. We are implementing a multidisciplinary pain management program based on biopsychosocial model guided by the IASP recommendations for such a program in Fukushima, Japan. The purpose of this study was to describe our initial efforts in creating a Japanese inpatient pain management program using the biopsychosocial method of self–pain management. The pain management center was started in April 2015 with a team consisting of ortho paedic surgeons, psychiatrists, nurses, physical therapists, clinical psychologists, pharmacists, and nutritionists. Our 3–week inpatient pain management program is indicated for patients who find it hard to work or go to school due to chronic musculoskeletal pain, and/or are confined to life at home but want to return to work or school. This program consists of exercise therapy, psychotherapy, and cognitive behavior al therapy. Using this program, our inpatients with intractable chronic muscu loskeletal pain were evaluated using brief pain inventory (BPI), pain catastrophizing scale (PCS) (rumination, magnification, and helplessness), pain disability assessment scale (PDAS), hospital anxiety and depression scale (HADS), pain self– efficacy questionnaire (PSEQ), EQ–5D, and physical functions (flexibility, muscle endurance, walking ability, and physical fitness). Statistical analyses were performed using the paired t–test and Wilcoxon matched pairs signed rank sum test with Bonferroni correction after Friedman test. Twenty–one patients (7 male and 14 female; 20–79 years old (Average 52.2 years old)) were analyzed from April 2015 to December 2017. Comparing results before and after the program, the following statistically significant improvement were seen in BPI, PCS (rumination, magnification, helplessness), PDAS, HADS anxiety and depression scale, PSEQ, EQ–5D, 30–sec sit to stand test (muscle endurance), 2 step test (walking ability), and 6–minute walking test","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":"42835469","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}
Phantom limb refers to a phenomenon whereby the patient still feels sensation and movements originating in the missing part after amputation. The patient is therefore aware of a part of the body that does not actually exist. The patient may also experience pain at this site, despite the actual body part not existing. Such a condition is referred to as phantom limb pain. Asomatognosia, however, refers to loss of awareness of a part of the body. It is a state in which the patient’s awareness of their body differs from reality. While this condition is normally widely–recognized as occurring after brain injury and right hemisphere damage in particular, it has been found to occur in many cases of neuropathic pain such as complex regional pain syndrome. In such cases, these are termed neglect–like symptoms. Thus, physical modification such as declines in sense of ownership and sense of agency may also be noted in motor disorders. Such cases involve dysfunction of the parietal lobe, which is involved in body representation. Therefore, in recent years, techniques for approaches to brain dysfunction similar to rehabilitation for stroke patients have been developed for cases of phantom limb not associated with brain damage and cases of motor disorders. The effects of such techniques are gradually being demonstrated. In this review, we described distorted body representation mechanisms from the viewpoints of neuro -phenomenology, neuropsychology and neurophysiology, and present the newly developed technique termed neurorehabilitation.
{"title":"Mechanisms of distorted body representation and neurorehabilitation","authors":"S. Morioka","doi":"10.11154/PAIN.34.10","DOIUrl":"https://doi.org/10.11154/PAIN.34.10","url":null,"abstract":"Phantom limb refers to a phenomenon whereby the patient still feels sensation and movements originating in the missing part after amputation. The patient is therefore aware of a part of the body that does not actually exist. The patient may also experience pain at this site, despite the actual body part not existing. Such a condition is referred to as phantom limb pain. Asomatognosia, however, refers to loss of awareness of a part of the body. It is a state in which the patient’s awareness of their body differs from reality. While this condition is normally widely–recognized as occurring after brain injury and right hemisphere damage in particular, it has been found to occur in many cases of neuropathic pain such as complex regional pain syndrome. In such cases, these are termed neglect–like symptoms. Thus, physical modification such as declines in sense of ownership and sense of agency may also be noted in motor disorders. Such cases involve dysfunction of the parietal lobe, which is involved in body representation. Therefore, in recent years, techniques for approaches to brain dysfunction similar to rehabilitation for stroke patients have been developed for cases of phantom limb not associated with brain damage and cases of motor disorders. The effects of such techniques are gradually being demonstrated. In this review, we described distorted body representation mechanisms from the viewpoints of neuro -phenomenology, neuropsychology and neurophysiology, and present the newly developed technique termed neurorehabilitation.","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":"43165399","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}
Phantom limb is a sensation of a missing hand that patients feel after amputation, and phantom limb pain or phantom pain is a pain in a phantom limb. Phantom limb pain occurs in 45 % – 85 % of amputees, and a part of them becomes refractory. Thus, it is needed to fully understand the pathophysiology of phantom limb pain for the devel-opment of effective treatments. To elucidate the central mechanisms of phantom limb pain, functional and anatomical changes in the brain has been explored by using non– invasive brain activity recording technique such as electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). In 1995 , Flor and colleagues reported that the somatotopic organization of the primary somatosensory cortex had altered in patients with phantom limb pain and the magnitude of this alteration had been associated with the intensity of their phantom limb pain. Based on these results, they proposed a model that alterations in the somatotopic organization of a missing hand are involved in phantom limb pain. Now, this model is known as the maladaptive reorganization model. Over the following 20 years, a variety of supporting evidence has been provided, and this model has been widely accepted. However, Makin and colleagues provided evidence against this model in 2013 . They demonstrated that cortical representation of a missing hand had been preserved and activation evoked by phantom limb movement had been related to the severity of phantom limb pain. After that, the maladaptive reorganization model has been revisited, and recent studies have suggested that functional alterations in the primary motor cortex rather than the primary sensory cortex are associated with phantom limb pain. Most recently, by using brain–machine interface technology, Yanagisawa and colleagues demonstrated that the activity of the missing hand area in the sensorimotor cortex is closely related to phantom limb pain. However, detailed neural mechanisms of phantom limb pain remain unclear so far, although many changes in the peripheral
{"title":"Functional and structural brain changes in patients with phantom limb pain","authors":"S. Kan","doi":"10.11154/PAIN.34.1","DOIUrl":"https://doi.org/10.11154/PAIN.34.1","url":null,"abstract":"Phantom limb is a sensation of a missing hand that patients feel after amputation, and phantom limb pain or phantom pain is a pain in a phantom limb. Phantom limb pain occurs in 45 % – 85 % of amputees, and a part of them becomes refractory. Thus, it is needed to fully understand the pathophysiology of phantom limb pain for the devel-opment of effective treatments. To elucidate the central mechanisms of phantom limb pain, functional and anatomical changes in the brain has been explored by using non– invasive brain activity recording technique such as electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). In 1995 , Flor and colleagues reported that the somatotopic organization of the primary somatosensory cortex had altered in patients with phantom limb pain and the magnitude of this alteration had been associated with the intensity of their phantom limb pain. Based on these results, they proposed a model that alterations in the somatotopic organization of a missing hand are involved in phantom limb pain. Now, this model is known as the maladaptive reorganization model. Over the following 20 years, a variety of supporting evidence has been provided, and this model has been widely accepted. However, Makin and colleagues provided evidence against this model in 2013 . They demonstrated that cortical representation of a missing hand had been preserved and activation evoked by phantom limb movement had been related to the severity of phantom limb pain. After that, the maladaptive reorganization model has been revisited, and recent studies have suggested that functional alterations in the primary motor cortex rather than the primary sensory cortex are associated with phantom limb pain. Most recently, by using brain–machine interface technology, Yanagisawa and colleagues demonstrated that the activity of the missing hand area in the sensorimotor cortex is closely related to phantom limb pain. However, detailed neural mechanisms of phantom limb pain remain unclear so far, although many changes in the peripheral","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":"44986433","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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