Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associ...Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.展开更多
Increasing evidence suggests that spinal micro- glia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain...Increasing evidence suggests that spinal micro- glia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain follow- ing intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID （a caspase-6 inhibitor） and the astroglial inhibitors L-α-aminoadipate （L-AA, an astroglial toxin） and car- benoxolone （a connexin 43 inhibitor）, as well as U0126 （an ERK kinase inhibitor） and D-JNKI-1 （a c-Jun N-terminal kinase inhibitor）. We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflam- matory pain in both sexes. Intrathecal U0126 and D-JNKI- 1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.展开更多
AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain.METHODS: The review process applied systematic evidence-based assessment methodol...AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain.METHODS: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including Pub Med from 1966 onwards, Cochrane library, National Guideline Clearinghouse, clinicaltrials.gov, along with other sources includingprevious systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional Pain Management Techniques- Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level Ⅰ to level Ⅴ.RESULTS: Across all databases, 16 high quality diagnostic accuracy studies were identified. In addition, multiple studies assessed the influence of multiple factors on diagnostic validity. In contrast to diagnostic validity studies, therapeutic efficacy trials were limited to a total of 14 randomized controlled trials, assessing the efficacy of intraarticular injections, facet or zygapophysial joint nerve blocks, and radiofrequency neurotomy of the innervation of the facet joints. The evidence for the diagnostic validity of lumbar facet joint nerve blocks with at least 75% pain relief with ability to perform previously painful movements was level Ⅰ, based on a range of level Ⅰ to Ⅴ derived from a best evidence synthesis. For therapeutic interventions, the evidence was variable from level Ⅱ to Ⅲ, with level Ⅱ evidence for lumbar facet joint nerve blocks and radiofrequency neurotomy for long-term improvement(greater than 6 mo), and level Ⅲ evidence for lumbosacral zygapophysial joint injections for short-term improvement only.CONCLUSION: This review provides significant evidence for the diagnostic validity of facet joint nerve blocks, and moderate evidence for therapeutic radiofrequency neurotomy and therapeutic facet joint nerve blocks in managing chronic low back pain.展开更多
Considerable clinical evidence has demonstrated that the prevalence and severity of many chronic pain syndromes differ across sex,and are more predominant in womenthan inmen[l]But most preclinical research on chronic ...Considerable clinical evidence has demonstrated that the prevalence and severity of many chronic pain syndromes differ across sex,and are more predominant in womenthan inmen[l]But most preclinical research on chronic pain mechanisms has been performed primarily in male animals.It is generally understood that inflammatory responses in the peripheral and central nervous systems are critical for chronic pain[2,3],Given that sex dimorphism influences immunity in various diseases[4].展开更多
Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of t...Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after amputation.This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery.In this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote CPAP.Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not afected.In the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-mice.Further study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the DRG.Interestingly,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve stump.Furthermore,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between nociceptors and macrophages,and that these two factors gang up together to regulate the formation of CPAP.This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.展开更多
Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain an...Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.展开更多
There are few conservative treatment options for adult patients with idiopathic scoliosis who are status post-fusion surgery. These typically include pharmacologic pain management, epidural injections, and generalized...There are few conservative treatment options for adult patients with idiopathic scoliosis who are status post-fusion surgery. These typically include pharmacologic pain management, epidural injections, and generalized CAM treatments such as massage and chiropractic manipulation in the non-fused areas of the spine. The purpose of this study was to compare the post-treatment results in an adult post-fusion patient who wore a scoliosis activity suit for 8 months. Pain was evaluated using a quadruple visual analog scale (QVAS), while function was measured using an SRS-22r questionnaire. After 8 months of wearing the scoliosis activity suit, her pain scores improved, here SRS-22r improved, and a significant correction in radiographic Cobb angle was observed. This case report is the first to document a Cobb angle change in an adult patient wearing a scoliosis activity suit who is status post-fusion. Given that pain and dysfunction are primary reasons for scoliosis treatment in the adult population, more studies need to address the disparity between available treatments for adult scoliosis and the incidence of adult scoliosis, especially in the post-meno-pausal population. Future prospective studies should consider evaluating treatment effects of this suit using intent-to-treat methodology.展开更多
Chronic pain is a major health problem world-wide. According to a recent report in the New England Journal of Medicine , the prevalence of pain in the United States is striking： more than 116 million Americans have p...Chronic pain is a major health problem world-wide. According to a recent report in the New England Journal of Medicine , the prevalence of pain in the United States is striking： more than 116 million Americans have pain that persist for weeks to years. Chronic pain is characterized as inflammatory pain, cancer pain, and neuropathic pain, and can result from such conditions as arthritis, cancer, diabe- tes, low back injury, surgery, viral infection, spinal cord injury, and stroke.展开更多
Recently there have been several major advances in our understanding of pathophysiological mechanisms in primary afferent nociceptors that may contribute to enhanced nociception (hyperalgesia) in response to injury, i...Recently there have been several major advances in our understanding of pathophysiological mechanisms in primary afferent nociceptors that may contribute to enhanced nociception (hyperalgesia) in response to injury, in a variety of clinical states. These include contributions of specific second messenger signaling pathways and ionic conductances. Important roles for specific second messenger systems in acute primary展开更多
Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as ...Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.展开更多
Background: Pharmacogenetics information about cytochrome p450 (CYP450) polymorphism in patients with headaches is limitedly reported. Similarly, the genetic factors linking various headache types and vascular disorde...Background: Pharmacogenetics information about cytochrome p450 (CYP450) polymorphism in patients with headaches is limitedly reported. Similarly, the genetic factors linking various headache types and vascular disorders are poorly described. We aimed to characterize the genetic profile of a cohort of headache and facial pain subjects. Methods: Medical records of consecutive headache subjects that underwent PersonaGeneTM testing were reviewed. PersonaGeneTM panel assessed CYP450, apolipoprotein E (ApoE), methylene tetrahydrofolate reductase (MTHFR), Factor II, Factor V Leiden and Vitamin K epoxide reductase complex subunit 1 (VKORC1). Demographic information, headache diagnosis and genetic profiling were analyzed and compared with data obtained from the general population. Results: Out of 130 headache patients, 91.3% were Caucasian and 70.8% had migraine. Compared to the general Caucasian population, our Caucasian headache patients were significantly different for CYP3A4/A5 and CYP2D6 (p < 0.001) and comparable regarding CYP2C9 and CYPC19. Whereas MTHFR genotype was similar, ApoE and Factor V Leiden were different in headache patients (p = 0.001). Less headache patients showed intermediate sensitivity to warfarin (p = 0.009) based on VQORC1 genotyping. No differences were noticed between migraine and other headache type diagnoses for all the genetic tests. Conclusion: Distinctive profiles for CYP450, ApoE, Factor V Leiden and VQORC1 were observed in our Caucasian headache cohort. These results may impact headache subjects’ pharmacological treatment options and vascular risk ascertainment.展开更多
Epidemiological surveys have recently revealed a high prevalence of chronic musculoskeletal pain in Japan;however, 30% of the patients in the survey were not satisfied with their pain treatment. This indicates that st...Epidemiological surveys have recently revealed a high prevalence of chronic musculoskeletal pain in Japan;however, 30% of the patients in the survey were not satisfied with their pain treatment. This indicates that standard strategies in the management of chronic pain are poorly shared among physicians in Japan. Herein we report a case of a patient with intractable chronic pain who is a skilled orthopaedic physician. A 43-year-old man who was a skilled orthopaedic surgeon presented at our center complaining of severe buttock pain especially around the right hip region for more than three years. At begging of pain onset, he was diagnosed with femoacetabular impingement syndrome (FAI) with labral tear. Despite biophysical interventions including twice surgeries and alternative conservative treatment, his pain persisted, and he occasionally had to take a day off work due to the severe pain. Therefore we had to evaluate his pathological condition using a multidimensional approach based on a biopsychosocial model. We had provided him with cognitive behavioral therapy (CBT) approach, and simultaneously suggestion for short leaving from work. Three months after the start of CBT training, his disabilities had begun to improve. About six months later, he could continue to do his work. Finally, 19 months have passed since we started implementing the CBT approach;he has regained both his previous work-life balance and his health, although the pain has not completely subsided. In conclusion, we think it is important for physicians treating chronic pain to learn the management strategies for chronic pain and to re-consider their management policy when conventional biomedical interventions were not succeeded, even in cases where medication and surgical intervention are warranted.展开更多
Scoliosis in adult patients is known to increase across the lifespan and increases the chance of chronic pain in later adulthood. Non-surgical scoliosis treatment options for adults are not widely recommended, largely...Scoliosis in adult patients is known to increase across the lifespan and increases the chance of chronic pain in later adulthood. Non-surgical scoliosis treatment options for adults are not widely recommended, largely due to lack of research in this area. Pain management options for adults are focused primarily on treating scoliosis-related pain, and not necessarily the scoliosis itself, such as epidural injections, prescription pain medications, and general physical therapy. Recent studies reporting non-surgical, scoliosis-specific treatment methods in adults are encouraging, but their study designs limit extrapolation. The current study reports the self-reported pain and radiographic outcomes in adult patients wearing a scoliosis activity suit for at least 10 years. A total of 22 patient charts that fulfilled the inclusion criteria were selected for review. Cobb angle radiographic measurements and self-rated quadruple numerical pain rating scale (QVAS) at baseline and 10-year follow-up were used as the outcomes. Cobb angle measurements were compared at baseline and 10 years and subdivided according to scoliosis curve pattern. At 10 years, 68% of patients had improvements in their Cobb angle > 5˚, with an overall average of approximately 9˚. Significant differences were also observed in the 10-year Cobb angle measurements when compared to the predicted 10-year Cobb angles based on the established rate of linear progression in adults. A statistically significant change was also observed in the 10-year QVAS scores. These results suggest a potential role of the scoliosis activity suit for improving Cobb angles in adults and reducing scoliosis-related pain.展开更多
BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysm...BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ROSC.METHODS:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014.Patients’general information,ETCO_(2),and POP parameters were collected and statistically analyzed.RESULTS:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes.The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),respectively.CONCLUSION:Patients with unsustained ROSC have a poor prognosis.The combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.展开更多
Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the e...Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.展开更多
Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief....Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.展开更多
Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment...Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.展开更多
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the US National Institutes of Health (R01-DE17794, R01-NS54362 and R01-NS67686)
文摘Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.
基金supported by NIH R01 grants DE17794,DE22743,and NS87988 to RRJsupported by NIH T32 2T32GM008600a Foundation of Anesthesia Education and Research Fellowship
文摘Increasing evidence suggests that spinal micro- glia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain follow- ing intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID （a caspase-6 inhibitor） and the astroglial inhibitors L-α-aminoadipate （L-AA, an astroglial toxin） and car- benoxolone （a connexin 43 inhibitor）, as well as U0126 （an ERK kinase inhibitor） and D-JNKI-1 （a c-Jun N-terminal kinase inhibitor）. We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflam- matory pain in both sexes. Intrathecal U0126 and D-JNKI- 1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.
文摘AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain.METHODS: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including Pub Med from 1966 onwards, Cochrane library, National Guideline Clearinghouse, clinicaltrials.gov, along with other sources includingprevious systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional Pain Management Techniques- Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level Ⅰ to level Ⅴ.RESULTS: Across all databases, 16 high quality diagnostic accuracy studies were identified. In addition, multiple studies assessed the influence of multiple factors on diagnostic validity. In contrast to diagnostic validity studies, therapeutic efficacy trials were limited to a total of 14 randomized controlled trials, assessing the efficacy of intraarticular injections, facet or zygapophysial joint nerve blocks, and radiofrequency neurotomy of the innervation of the facet joints. The evidence for the diagnostic validity of lumbar facet joint nerve blocks with at least 75% pain relief with ability to perform previously painful movements was level Ⅰ, based on a range of level Ⅰ to Ⅴ derived from a best evidence synthesis. For therapeutic interventions, the evidence was variable from level Ⅱ to Ⅲ, with level Ⅱ evidence for lumbar facet joint nerve blocks and radiofrequency neurotomy for long-term improvement(greater than 6 mo), and level Ⅲ evidence for lumbosacral zygapophysial joint injections for short-term improvement only.CONCLUSION: This review provides significant evidence for the diagnostic validity of facet joint nerve blocks, and moderate evidence for therapeutic radiofrequency neurotomy and therapeutic facet joint nerve blocks in managing chronic low back pain.
基金supported by National Natural Science Foundation of China(81771204)the Natural Science Foundation of Guangdong Province(2019A1515011838,2020A1515010204,2021A1515011742,and 2021A1515011742).
文摘Considerable clinical evidence has demonstrated that the prevalence and severity of many chronic pain syndromes differ across sex,and are more predominant in womenthan inmen[l]But most preclinical research on chronic pain mechanisms has been performed primarily in male animals.It is generally understood that inflammatory responses in the peripheral and central nervous systems are critical for chronic pain[2,3],Given that sex dimorphism influences immunity in various diseases[4].
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203201)the National Natural Science Foundation of China(81971034,81672237)+3 种基金The Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Pujiang Program(19PJ1401700)the Natural Science Foundation of Shanghai Municipality(22ZR1413800)The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology,Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202008).
文摘Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after amputation.This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery.In this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote CPAP.Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not afected.In the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-mice.Further study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the DRG.Interestingly,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve stump.Furthermore,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between nociceptors and macrophages,and that these two factors gang up together to regulate the formation of CPAP.This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
基金supported by National Institutes of Health Grants R01NS89479,R01NS045594 and ROINS055860
文摘Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
文摘There are few conservative treatment options for adult patients with idiopathic scoliosis who are status post-fusion surgery. These typically include pharmacologic pain management, epidural injections, and generalized CAM treatments such as massage and chiropractic manipulation in the non-fused areas of the spine. The purpose of this study was to compare the post-treatment results in an adult post-fusion patient who wore a scoliosis activity suit for 8 months. Pain was evaluated using a quadruple visual analog scale (QVAS), while function was measured using an SRS-22r questionnaire. After 8 months of wearing the scoliosis activity suit, her pain scores improved, here SRS-22r improved, and a significant correction in radiographic Cobb angle was observed. This case report is the first to document a Cobb angle change in an adult patient wearing a scoliosis activity suit who is status post-fusion. Given that pain and dysfunction are primary reasons for scoliosis treatment in the adult population, more studies need to address the disparity between available treatments for adult scoliosis and the incidence of adult scoliosis, especially in the post-meno-pausal population. Future prospective studies should consider evaluating treatment effects of this suit using intent-to-treat methodology.
文摘Chronic pain is a major health problem world-wide. According to a recent report in the New England Journal of Medicine , the prevalence of pain in the United States is striking： more than 116 million Americans have pain that persist for weeks to years. Chronic pain is characterized as inflammatory pain, cancer pain, and neuropathic pain, and can result from such conditions as arthritis, cancer, diabe- tes, low back injury, surgery, viral infection, spinal cord injury, and stroke.
文摘Recently there have been several major advances in our understanding of pathophysiological mechanisms in primary afferent nociceptors that may contribute to enhanced nociception (hyperalgesia) in response to injury, in a variety of clinical states. These include contributions of specific second messenger signaling pathways and ionic conductances. Important roles for specific second messenger systems in acute primary
基金the National Natural Science Foundation of China(81772386,81702191,81572175,81371984,and 81071511)the Guangdong-Hong Kong Joint Innovation Project of Guangdong Province(2017A050506019)the Natural Science Foundation of Guangdong Province,China(2020A1515011031).
文摘Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.
文摘Background: Pharmacogenetics information about cytochrome p450 (CYP450) polymorphism in patients with headaches is limitedly reported. Similarly, the genetic factors linking various headache types and vascular disorders are poorly described. We aimed to characterize the genetic profile of a cohort of headache and facial pain subjects. Methods: Medical records of consecutive headache subjects that underwent PersonaGeneTM testing were reviewed. PersonaGeneTM panel assessed CYP450, apolipoprotein E (ApoE), methylene tetrahydrofolate reductase (MTHFR), Factor II, Factor V Leiden and Vitamin K epoxide reductase complex subunit 1 (VKORC1). Demographic information, headache diagnosis and genetic profiling were analyzed and compared with data obtained from the general population. Results: Out of 130 headache patients, 91.3% were Caucasian and 70.8% had migraine. Compared to the general Caucasian population, our Caucasian headache patients were significantly different for CYP3A4/A5 and CYP2D6 (p < 0.001) and comparable regarding CYP2C9 and CYPC19. Whereas MTHFR genotype was similar, ApoE and Factor V Leiden were different in headache patients (p = 0.001). Less headache patients showed intermediate sensitivity to warfarin (p = 0.009) based on VQORC1 genotyping. No differences were noticed between migraine and other headache type diagnoses for all the genetic tests. Conclusion: Distinctive profiles for CYP450, ApoE, Factor V Leiden and VQORC1 were observed in our Caucasian headache cohort. These results may impact headache subjects’ pharmacological treatment options and vascular risk ascertainment.
文摘Epidemiological surveys have recently revealed a high prevalence of chronic musculoskeletal pain in Japan;however, 30% of the patients in the survey were not satisfied with their pain treatment. This indicates that standard strategies in the management of chronic pain are poorly shared among physicians in Japan. Herein we report a case of a patient with intractable chronic pain who is a skilled orthopaedic physician. A 43-year-old man who was a skilled orthopaedic surgeon presented at our center complaining of severe buttock pain especially around the right hip region for more than three years. At begging of pain onset, he was diagnosed with femoacetabular impingement syndrome (FAI) with labral tear. Despite biophysical interventions including twice surgeries and alternative conservative treatment, his pain persisted, and he occasionally had to take a day off work due to the severe pain. Therefore we had to evaluate his pathological condition using a multidimensional approach based on a biopsychosocial model. We had provided him with cognitive behavioral therapy (CBT) approach, and simultaneously suggestion for short leaving from work. Three months after the start of CBT training, his disabilities had begun to improve. About six months later, he could continue to do his work. Finally, 19 months have passed since we started implementing the CBT approach;he has regained both his previous work-life balance and his health, although the pain has not completely subsided. In conclusion, we think it is important for physicians treating chronic pain to learn the management strategies for chronic pain and to re-consider their management policy when conventional biomedical interventions were not succeeded, even in cases where medication and surgical intervention are warranted.
文摘Scoliosis in adult patients is known to increase across the lifespan and increases the chance of chronic pain in later adulthood. Non-surgical scoliosis treatment options for adults are not widely recommended, largely due to lack of research in this area. Pain management options for adults are focused primarily on treating scoliosis-related pain, and not necessarily the scoliosis itself, such as epidural injections, prescription pain medications, and general physical therapy. Recent studies reporting non-surgical, scoliosis-specific treatment methods in adults are encouraging, but their study designs limit extrapolation. The current study reports the self-reported pain and radiographic outcomes in adult patients wearing a scoliosis activity suit for at least 10 years. A total of 22 patient charts that fulfilled the inclusion criteria were selected for review. Cobb angle radiographic measurements and self-rated quadruple numerical pain rating scale (QVAS) at baseline and 10-year follow-up were used as the outcomes. Cobb angle measurements were compared at baseline and 10 years and subdivided according to scoliosis curve pattern. At 10 years, 68% of patients had improvements in their Cobb angle > 5˚, with an overall average of approximately 9˚. Significant differences were also observed in the 10-year Cobb angle measurements when compared to the predicted 10-year Cobb angles based on the established rate of linear progression in adults. A statistically significant change was also observed in the 10-year QVAS scores. These results suggest a potential role of the scoliosis activity suit for improving Cobb angles in adults and reducing scoliosis-related pain.
基金supported by National Natural Science Foundation of China General Program (82172179)Mathematics Tianyuan Fund (12126604)Central High-level Hospital Clinical Research Project (2022-PUMCH-B-110)
文摘BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ROSC.METHODS:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014.Patients’general information,ETCO_(2),and POP parameters were collected and statistically analyzed.RESULTS:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes.The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),respectively.CONCLUSION:Patients with unsustained ROSC have a poor prognosis.The combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.
文摘Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.
基金Supported by Sichuan Science and Technology Program,No.2018SZ0386。
文摘Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.
文摘Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.
