In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these...In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these topics[6],featuring single-cell profiling and in vivo Ca2+imaging of primary sensory neurons[7,8],and illustrating how nociceptors regulate pain,itch,and infection[9].It also highlighted spinal neurocircuits of pain[10]and itch[11],glial contributions[12],sex differences[13],and supraspinal mechanisms underlying pain and empathy[14,15].Over the past seven years,significant advances have been made in neuroglial and neuroimmune interactions and supraspinal circuits.Thus,this third special issue—comprising one review,eleven original articles,and one research highlight[16,17,18,19,20,21,22,23,24,25,26,27,28]—timely summarizes recent progress in pain and itch research.展开更多
Advances of studies on the acupuncture and pain signal transduction mechanisms in complete Freud＇s adjuvant arthritis are reviewed from the three aspects, the first messenger of modulating pain signals and the relate...Advances of studies on the acupuncture and pain signal transduction mechanisms in complete Freud＇s adjuvant arthritis are reviewed from the three aspects, the first messenger of modulating pain signals and the related receptors, the second messenger of modulating pain signals and other factors possibly involved in modulation of pain signal transduction, etc. It is held that modulation of acupuncture for pain signals is a comprehensive course involved in multi-channels, multi-levels, multi-links, and in future, acupuncture analgesic mechanisms for Freud＇s adjuvant arthritis will be more deeply studied by use of more new techniques and new methods.展开更多
In 2012, we published the first special issue on mechanisms of pain and itch in Neuroscience Bulletin, which covered the peripheral, central, and glial mechanisms of pain and itch [1-5]. In the last 5 years, the field...In 2012, we published the first special issue on mechanisms of pain and itch in Neuroscience Bulletin, which covered the peripheral, central, and glial mechanisms of pain and itch [1-5]. In the last 5 years, the field has seen tremendous progress in the molecular and functional characterization of primary sensory neurons [6, 7], neurocircuits of pain and itch [8-10], immune and glial modulation of pain and itch [11-15], molecular mechanisms of pain [16, 17], and identification of brain signatures of pain [18]. Thus, it is timely to highlight the recent progress in a second special issue. I invited the previous authors and new authors from China, the USA, and Japan, and they have contributed 20 mini-reviews and original articles to this special issue.展开更多
In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale whi...In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.展开更多
Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and cha...Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV（ITC） injection. Then, we evaluated the efficacy of gabapentin（GBP）, an anticonvulsant that binds the voltage-gated Ca2＋ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration（1, 10, or 100 mg/kg） on day 7 post-ITC, with significant effects lasting at least 5 hfor the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness（drug tolerance） at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.展开更多
BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-rep...BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-reported LBP.No study has previously investigated whether exposure to prolonged flexed sitting posture provokes discomfort/pain and decreased interspinous pressure pain thresholds for healthy young men and women without back pain,despite this being a suggested risk factor for LBP.AIM To investigate whether sitting in a prolonged flexed lumbar posture provokes discomfort and lowers interspinous pressure pain thresholds in the lumbar spine for healthy young men and women without previous LBP.METHODS This is a an observational before and after study of 26 participants(13 men,13 women)between 20-35 years old.Algometry was used to examine the pain threshold for pressure applied between spinous processes of the lumbar spine L1-L5.Pressure algometer measures were performed in prone before and after participants were instructed to sit in a fully flexed posture for a maximum of 15 min or until discomfort was experienced in the low back(Borg CR10=7/10).Wilcoxon signed-rank test was used for analyze values from the before and after test conditions.Mann-Whitney U test was used to investigate potential gender difference.RESULTS Fully flexed lumbar spine sitting posture up to 15 min provoked temporary discomfort but the proportion of participants experiencing discomfort 7/10 in the low back was 62%.For all pain pressure threshold locations tested,there was a significant difference for the study population with moderate-large decreased(r=-0.56)pressure pain threshold after exposure to prolonged flexed sitting posture(P<0.01).Comparisons between gender did not show any significant difference.CONCLUSION The result showed that exposure to fully flexed lumbar sitting posture for up to 15 min produced temporary discomfort in the low back in young healthy adults with no previous history of LBP and significantly reduced lumbar interspinous pressure pain thresholds.No gender-based differences were observed.展开更多
An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to ...An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to create conscious interoception. Especially with regard to pain experience, the IC has been supposed to participate in both sensory-discriminative and affective-motivational aspects of pain. In this review, we discuss the latest data proposing that subregions of the IC are involved in isolated pain networks： the posterior sensory circuit and the anterior emotional network. Due to abundant connections with other brain areas, the IC is likely to serve as an interface where cross-modal shaping of pain occurs. In chronic pain,however, this mode of emotional awareness and the modulation of pain are disrupted. We highlight some of the molecular mechanisms underlying the changes of the pain modulation system that contribute to the transition from acute to chronic pain in the IC.展开更多
Most of the orthodontic patients experience pain during treatment and this significantly influences their attitudes and the approach towards treatment. A number of factors that influence pain response include age, gen...Most of the orthodontic patients experience pain during treatment and this significantly influences their attitudes and the approach towards treatment. A number of factors that influence pain response include age, gender, personal pain threshold, mood and stress level of the person, cultural differences and types of orthodontic treatment. Pain is a often overlooked subject by orthodontists, it is nevertheless important to understand the source and mechanism of the pain that occurs during treatment, as well as the methods for managing and controlling this pain. This review attempts to overview the mechanism, duration and current management strategies of orthodontic treatment.展开更多
Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effec...Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.展开更多
Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pai...Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.展开更多
Mechanical pain is one of the most common causes of clinical pain,but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain.Recently,neurotoxin GsMTx4,a selectiv...Mechanical pain is one of the most common causes of clinical pain,but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain.Recently,neurotoxin GsMTx4,a selective mechanosensitive(MS)channel inhibitor,has been found to be effective,while the underlying mechanism remains elusive.Here,with multiple rodent pain models,we demonstrated that a GsMTx4-based 17-residue peptide,which we call P10581,was able to reduce mechanical hyperalgesia and neuropathic pain.The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models.The anti-hyperalgesic effect of the peptide was resistant to naloxone(anμ-opioid receptor antagonist)and showed no side effects of morphine,including tolerance,motor impairment,and conditioned place preference.Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system,combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581.Our study identified a potential drug for curing mechanical pain and exposed its mechanism.展开更多
文摘In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these topics[6],featuring single-cell profiling and in vivo Ca2+imaging of primary sensory neurons[7,8],and illustrating how nociceptors regulate pain,itch,and infection[9].It also highlighted spinal neurocircuits of pain[10]and itch[11],glial contributions[12],sex differences[13],and supraspinal mechanisms underlying pain and empathy[14,15].Over the past seven years,significant advances have been made in neuroglial and neuroimmune interactions and supraspinal circuits.Thus,this third special issue—comprising one review,eleven original articles,and one research highlight[16,17,18,19,20,21,22,23,24,25,26,27,28]—timely summarizes recent progress in pain and itch research.
基金Supported by Scientific Research Project Foundation of Shanghai City Science and Technology Committee:07dz19722-5
文摘Advances of studies on the acupuncture and pain signal transduction mechanisms in complete Freud＇s adjuvant arthritis are reviewed from the three aspects, the first messenger of modulating pain signals and the related receptors, the second messenger of modulating pain signals and other factors possibly involved in modulation of pain signal transduction, etc. It is held that modulation of acupuncture for pain signals is a comprehensive course involved in multi-channels, multi-levels, multi-links, and in future, acupuncture analgesic mechanisms for Freud＇s adjuvant arthritis will be more deeply studied by use of more new techniques and new methods.
文摘In 2012, we published the first special issue on mechanisms of pain and itch in Neuroscience Bulletin, which covered the peripheral, central, and glial mechanisms of pain and itch [1-5]. In the last 5 years, the field has seen tremendous progress in the molecular and functional characterization of primary sensory neurons [6, 7], neurocircuits of pain and itch [8-10], immune and glial modulation of pain and itch [11-15], molecular mechanisms of pain [16, 17], and identification of brain signatures of pain [18]. Thus, it is timely to highlight the recent progress in a second special issue. I invited the previous authors and new authors from China, the USA, and Japan, and they have contributed 20 mini-reviews and original articles to this special issue.
文摘In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.
基金supported by grants from the National Natural Science Foundation of China (81171049)the National Basic Research Development Program of China (2011CB504100,2013CB835100 and 2013BAI04B04)
文摘Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV（ITC） injection. Then, we evaluated the efficacy of gabapentin（GBP）, an anticonvulsant that binds the voltage-gated Ca2＋ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration（1, 10, or 100 mg/kg） on day 7 post-ITC, with significant effects lasting at least 5 hfor the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness（drug tolerance） at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.
文摘BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-reported LBP.No study has previously investigated whether exposure to prolonged flexed sitting posture provokes discomfort/pain and decreased interspinous pressure pain thresholds for healthy young men and women without back pain,despite this being a suggested risk factor for LBP.AIM To investigate whether sitting in a prolonged flexed lumbar posture provokes discomfort and lowers interspinous pressure pain thresholds in the lumbar spine for healthy young men and women without previous LBP.METHODS This is a an observational before and after study of 26 participants(13 men,13 women)between 20-35 years old.Algometry was used to examine the pain threshold for pressure applied between spinous processes of the lumbar spine L1-L5.Pressure algometer measures were performed in prone before and after participants were instructed to sit in a fully flexed posture for a maximum of 15 min or until discomfort was experienced in the low back(Borg CR10=7/10).Wilcoxon signed-rank test was used for analyze values from the before and after test conditions.Mann-Whitney U test was used to investigate potential gender difference.RESULTS Fully flexed lumbar spine sitting posture up to 15 min provoked temporary discomfort but the proportion of participants experiencing discomfort 7/10 in the low back was 62%.For all pain pressure threshold locations tested,there was a significant difference for the study population with moderate-large decreased(r=-0.56)pressure pain threshold after exposure to prolonged flexed sitting posture(P<0.01).Comparisons between gender did not show any significant difference.CONCLUSION The result showed that exposure to fully flexed lumbar sitting posture for up to 15 min produced temporary discomfort in the low back in young healthy adults with no previous history of LBP and significantly reduced lumbar interspinous pressure pain thresholds.No gender-based differences were observed.
基金supported by the National Natural Science Foundation of China(31371120)the Foundation for Returned Overseas Students of Ministry of Education,China(HG3503)
文摘An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to create conscious interoception. Especially with regard to pain experience, the IC has been supposed to participate in both sensory-discriminative and affective-motivational aspects of pain. In this review, we discuss the latest data proposing that subregions of the IC are involved in isolated pain networks： the posterior sensory circuit and the anterior emotional network. Due to abundant connections with other brain areas, the IC is likely to serve as an interface where cross-modal shaping of pain occurs. In chronic pain,however, this mode of emotional awareness and the modulation of pain are disrupted. We highlight some of the molecular mechanisms underlying the changes of the pain modulation system that contribute to the transition from acute to chronic pain in the IC.
文摘Most of the orthodontic patients experience pain during treatment and this significantly influences their attitudes and the approach towards treatment. A number of factors that influence pain response include age, gender, personal pain threshold, mood and stress level of the person, cultural differences and types of orthodontic treatment. Pain is a often overlooked subject by orthodontists, it is nevertheless important to understand the source and mechanism of the pain that occurs during treatment, as well as the methods for managing and controlling this pain. This review attempts to overview the mechanism, duration and current management strategies of orthodontic treatment.
基金National Natural Science Foundation of China,Nos.82302877(to QW),82172541(to TW)the Natural Science Foundation of Hunan Province,No.2023JJ30549(to QW)Clinical Medical Technology Innovation Guidance Project of Hunan Provincial Science and Technology Department,No.2021SK51815(to QW).
文摘Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.
基金supported by the National Natural Science Foundation of China,No.81671891
文摘Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.
基金supported by NSFC grants(81450064,82371233,China)QiongYao Tang,NSFC grants(81471314,81671090,China)+3 种基金Zhe Zhang.Luzhou Science and Technology Bureau(2021-SYF-28,China)Southwest Medical University of China(2021ZKMS033)grants to Mingxi Tang,Key Project in Sichuan province department of education to Mingxi Tang(16ZA0196,China)Jiangsu specially appointed professorship to QiongYao Tang and Zhe Zhang.
文摘Mechanical pain is one of the most common causes of clinical pain,but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain.Recently,neurotoxin GsMTx4,a selective mechanosensitive(MS)channel inhibitor,has been found to be effective,while the underlying mechanism remains elusive.Here,with multiple rodent pain models,we demonstrated that a GsMTx4-based 17-residue peptide,which we call P10581,was able to reduce mechanical hyperalgesia and neuropathic pain.The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models.The anti-hyperalgesic effect of the peptide was resistant to naloxone(anμ-opioid receptor antagonist)and showed no side effects of morphine,including tolerance,motor impairment,and conditioned place preference.Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system,combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581.Our study identified a potential drug for curing mechanical pain and exposed its mechanism.
