Growing pains: What do we know about etiology? A systematic review

BACKGROUND Growing pains is the most common cause of musculoskeletal pain in early childhood and was first described in 1823 by French physician Marcel Duchamp.Although it has been researched extensively, the etiology is still unknown.Several theories have been proposed throughout the years.AIM Analyze the available scientific literature to provide an update on the latest evidence on the etiology.METHODS According to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the scientific literature on the etiology of growing pains was systematically reviewed using the following inclusion criteria: studies of any level of evidence reporting clinical or preclinical results and dealing with the etiology of growing pains. The medical electronic databases PubMed and Web of Science were searched by two independent authors on October 20, 2018.The search string used was "(growing pains OR benign nocturnal limb pains OR musculoskeletal pains) AND(etiology OR pathogenesis) AND(pediatrics)".RESULTS A total of 32 articles were included. The etiology of growing pains still remains poorly understood. Many theories have been proposed, but none of them are decisive. A lower pain threshold has been found among patients suffering from growing pains in comparison to healthy controls. Furthermore, evidence suggests an association between growing pains and reduced bone strength in young patients, although this finding still remains controversial. Changes in the vascular perfusion pattern have also been studied. However, the etiology of growing pains does not seem related to a vascular component. The anatomical/mechanical theory has not been supported, but the role of vitamin D deficiency has been investigated many times. Strong recent evidence indicates a genetic susceptibility in the pathogenesis of growing pains. Furthermore,psychological factors also seem to play a strong role in the onset.CONCLUSION The scientific literature about the etiology of growing pains presents heterogeneity and lack of consensus; more studies are needed to understand the genesis of benign musculoskeletal pain syndrome of childhood.

Current trends and hotspots of etiology of auditory neuropathy in the past 30 years: A bibliometric analysis

Objective:To make an overview of global research trends in the etiology of auditory neuropathy(AN)over the past 30 years using a bibliometric approach.Methods:Bibliometric analyses were conducted by GraphPad Prism 9.0,Citespace 6.2.R2,and an online analysis platform to analyze and visualize publications related to etiology of AN from the Web of Science Core Collection(WoSCC)database from 1996 to 2022.Additionally,genetic factors in human AN were analyzed.Results:In total,604 original articles and reviews related to the etiology of AN from the WoSCC were included for bibliometric analysis.The results showed that annual publications and trend on etiology of AN increased linearly from 2000.Among them,the United States and China published nearly 400 records(40.32%).From the 604 records,a total of 752 keywords and 10 clustered network maps were extracted by Citespace,and‘mutations’was among the top 10 keywords.Analysis of genetic factors found that more than 30 genes were related to AN,and the latest burst occurred in 2022.Conclusion:The bibliometric analysis mapped the global research trends and analyzed hotspots for future.The results indicated that the annual publications increased linearly from 2000.Notably,there was a burst in genetic factors in 2022,which identified that genetic factor would remain a focus of future research.

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.

Etiology and pathogenesis of corona virus disease 2019 on the view of Chinese medicine

Traditional Chinese Medicine has played an important role in the prevention and treatment of the Corona Virus Disease 2019 epidemic.But in views of different TCM scholars there are different opinions about disease name,characteristic of etiology,law of pathogenesis about this epidemic.Based on related literatures,this article overviews of the characteristics of TCM etiology,law of pathogenesis and methods of syndrome differentiation,hoping to find research method that fit in with TCM clinical practice.Prerequisite of treatment is identifying the cause.The clinical manifestations of patients are important to TCM,and the etiological attributes can be inferred from the clinical manifestations.SARS-CoV-2 belongs to exogenous etiological factors,but there are different opinions about its characteristics of six pathogenic factors.Cold,Dampness,Warm,Dry,Toxin,Summer-heat,Wind,are all involved.Thus,different understanding of the pathogenesis and the law of transmission is caused.Such as cold and dampness hurt Yang,furthermore,consumed of Qi;dampness and toxin infected from external environment,turbid dampness produced inside the body;dryness affecting lungs and consume of Yin;warm-heat-turbid-toxin affected lungs,stomach and intestine;and then produced phlegm stagnation or blood stasis,furthermore consumed Qi and Yin.Based on those differences,methods of syndrome differentiation in treatment of COVID-19 are diverse,which contain pattern differentiation of zang-fu organs,pattern differentiation of Wei-defence,Qi,Ying nutrients and blood;pattern differentiation by the eight principles,and pattern differentiation of six meridians.Because of SARS-CoV-2 can spread to the whole country or even the whole world in a short period of time,its pathogenic nature should be roughly the same.So studying the treatment of COVID-19 based on clinical cases,refining the similarities and differences in the clinical presentation of patients with different subtypes during the epidemic,clarification of the etiologic attribution and evolutionary patterns of disease mechanisms,developing a comprehensive understanding of COVID-19 in Chinese medicine is needed.Furthermore,getting a full understanding of COVID-19,and providing reference for the prevention and treatment of unknown infectious diseases.

Genetic regulation of cell type-specific chromatin accessibility shapes brain disease etiology

Nucleotide variants in cell type-specific gene regulatory elements in the human brain are risk factors for human disease.We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci(caQTLs).Only 10.4%of caQTLs are shared between neurons and non-neurons,which supports cell type-specific genetic regulation of the brain regulome.Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk.Using massively parallel reporter assays in induced excitatory neurons,we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants.Combined,this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.

Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

Lighting the shades of hidden pain:a role for spinal cord neurons and microglia in vestibulodynia

Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain that significantly affects the quality of life of afflicted women.The present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.

Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain

Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.

Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain

Purpose: The ubiquitous use of synthetic materials in hernia surgery has brought about a new clinical syndrome: Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of slow onset, unsuspected and enigmatic to clinicians;irreversible because the pain is progressive, unrelenting and unresponsive to treatment. Removal of the mesh does not guarantee pain relief. Neuralgia following mesh insertion, when it occurs, remains a poorly understood phenomenon. Methods: Ten specimens in each group: virgin tissue, scar tissue and explanted mesh from the posterior inguinal wall were examined histologically to assess nerve density, nerve size and nerve and vessel ingrowth into the deformed mesh and within its pores. Results: There was no significant difference in nerve density between virgin, scar and mesh samples. All of the explanted meshes had nerves within the scar tissue encasing the mesh (interstitial infiltration). Nerve ingrowth through the pores of the mesh (micro-entrapment) was detected in 90% of the explanted mesh specimens. Additionally, nerves were detected entrapped within the folds and deformations of mesh explants. Ingrown vessels showed congestion and focal fibrin thrombi. Conclusion: The presence of mesh does not significantly affect nerve density, while the nerves and their terminal ends are in a vulnerable position about the mesh and within its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature, nerves and their receptors are exposed to potential mechanical and chemical factors: scarring, entrapment, compression, tugging, deformation, contraction, hypoxia/acidosis, inflammation and edema.

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

Intravenous Hydrogen Peroxide for Chronic Pain: An Alternative Etiology and Treatment Plan for the Long-Standing Painful States

Background: Anecdotal reports of improvement in chronic pain patients given oxidative therapy (OXT) in the form of Intravenous Hydrogen Peroxide (IVHP) led the author to try this therapy on intractable pain cases. Method: 54 intractable non-malignant pain cases selected at random (16 had spinal problems, 14 had Interstitial Cystitis, 8 had headaches and 16 with miscellaneous problems) each received an average of 9 weekly IVHP infusions of 250 ml 0.03% Hydrogen Peroxide. After 4 months of this therapy all patients were given a questionnaire to evaluate and study any improvements in their condition. The questions covered three areas: 1) Subjective improvements: pain, function, mental and emotional status, general health, and sexual health, 2) Analgesic medication usage: dosage and efficacy changes, 3) Satisfaction with the therapy and desire to continue. Results: 52%-70% mean 66% of the patients responded positively (more than slightly improved) to questions in the subjective areas, 85% of the patients were using less medication and/ or getting more effect from the analgesics they were taking, 96% of the patients wished to continue the therapy. These improvements were constant over the range of the four diagnostic groups. The improved patients all demonstrated some signs and lab results including fever, chills, abscess formation, purulent discharges, elevated WBCs and ESRs consistent with resolving systemic and/ or regional infections. Conclusions: IVPH can significantly improve patients in a majority of chronic painful conditions. Chronic Infection is associated with or absolutely the cause of Chronic Pain in the patients studied.

Tietze’s Syndrome in the emergency department: A rare etiology of atraumatic chest pain

Tietze’s Syndrome is an uncommon disorder that presents with painful, tender, non-suppurative swelling of the anterior chest wall. We report a case of a female patient who presented to the emergency department with a chief complaint of atraumatic chest pain and swelling of the anterior chest wall. After a thorough history and physical examination, as well as basic laboratory tests and chest radiography, she was diagnosed with Tietze’s Syndrome. The expedient accurate diagnosis of Tietze’s Syndrome is important for the physical and emotional well-being of a patient, and avoids overlooking more dangerous pathologies. Tietze’s Syndrome needs to be considered in the differential diagnosis of a patient presenting with spontaneous swelling of the anterior chest.

Application of Etiology List in Differential Diagnosis of Acute Abdominal Pain^#

Objective: To use the etiology list of abdominal pain to help identify acute abdominal pain. Methods: to design a list of causes of acute abdominal pain as per the concept of system thinking, determine the five differential diagnosis directions of “local organ disease, adjacent organ disease, systemic disease, psychogenic disease, and female reproductive system disease”, and elaborate the application effect of the checklist in the diagnosis of acute abdominal pain by virtue of the analysis of one case of acute abdominal pain. Results: according to the list of causes of abdominal pain, the causes of acute abdominal pain were screened, and patients suffering from acute renal infarction (ARI) who presented with simple abdominal pain were diagnosed and treated timely. Conclusion: the etiology list is helpful to guide the diagnosis direction of acute abdominal pain, and make a rapid clinical diagnosis, so as to form a systematic thinking mode.

Obturator hernia-a rare etiology of lateral thigh pain:A case report

BACKGROUND Lateral thigh pain is a common complaint in patients visiting a pain clinic.Herein,we describe the case of a patient with lateral thigh pain caused by an obturator hernia.CASE SUMMARY An 83-year-old woman visited the emergency room with suddenly aggravated right lateral thigh pain.Magnetic resonance imaging of the thigh revealed no abnormal findings in the lateral thigh area.However,an obturator hernia between the pectineus and obturator externus muscles was observed by chance.Retroperitoneal computed tomography revealed a herniated small bowel with an incarceration point at the right obturator canal and a dilated loop of the small bowel upstream.Ultrasonography of the right inguinal region revealed a distended bowel loop in the right pectineus muscle.CONCLUSION Our report provides clinicians with information that an obturator hernia can cause lateral thigh pain.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.

重型创伤性脑损伤去骨瓣减压应用改良Paine点穿刺监测脑室内颅内压的优势

目的探讨重型创伤性脑损伤(TBI)开颅去骨瓣减压术(DC)中应用改良Paine点穿刺行脑室内颅内压(ICP)监测探头置入的优势。方法回顾性分析2020年4月-2022年4月嘉兴市第二医院收治的48例重型TBI患者的临床资料。所有患者均行DC联合脑室内ICP监护术,按照ICP监测术式的不同,分为观察组(23例)与对照组(25例),其中观察组行DC切口内改良Paine点穿刺脑室内ICP监测探头置入术,对照组行传统DC对侧切口颅骨钻孔经Kocher点脑室内ICP监测探头置入术。比较两组术前一般资料、手术用时、术后甘露醇使用剂量及持续时间、ICP监测持续时间、术后再出血率、颅内感染率、术后3个月时格拉斯哥预后评分(GOS)。结果两组一般资料、甘露醇使用剂量、甘露醇持续时间和ICP监测持续时间比较差异均无统计学意义(P>0.05);观察组手术用时、术后再出血率、颅内感染率明显少于或低于对照组(P<0.05);两组术后3个月GOS评分比较差异无统计学意义(P>0.05)。结论相较传统的DC对侧切口颅骨钻孔经Kocher点行脑室内ICP监测探头置入术,重型脑外伤DC术中通过切口内改良Paine点穿刺行脑室内ICP监测探头置入术可缩短手术用时,降低术后再出血率、颅内感染率。

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.