New insight into the vasto-adductor membrane for safer adductor canal blockade.

Background: : This study aimed to identify exact anatomical landmarks and ideal injection volumes for safe adductor canal blocks (ACB). Methods: : Fifty thighs from 25 embalmed adult Korean cadavers were used. The measurement baseline was the line connecting the anterior superior iliac spine (ASIS) to the midpoint of the patellar base. All target points were measured perpendicular to the baseline. The relevant cadaveric structures were observed using ultrasound (US) and confirmed in living individuals. US-guided dye injection was performed to determine the ideal volume. Results: : The apex of the femoral triangle was 25.3 ± 2.2 cm distal to the ASIS on the baseline and 5.3 ± 1.0 cm perpendicular to that point. The midpoint of the superior border of the vasto-adductor membrane (VAM) was 27.4 ± 2.0 cm distal to the ASIS on the baseline and 5.0 ± 1.1 cm perpendicular to that point. The VAM had a trapezoidal shape and was connected as an aponeurosis between the medial edge of the vastus medialis muscle and lateral edge of the adductor magnus muscle. The nerve to the vastus medialis penetrated the muscle proximal to the superior border of the VAM in 70% of specimens. The VAM appeared on US as a hyperechoic area connecting the vastus medialis and adductor magnus muscles between the sartorius muscle and femoral artery. Conclusions: : Confirming the crucial landmark, the VAM, is beneficial when performing ACB. It is advisable to insert the needle obliquely below the superior VAM border, and a 5 mL injection is considered sufficient.

Comparison of international medical costs for interventional pain treatment: a focus on Korea and Japan.

Background: The rise in national health care costs has emerged as a global problem given the ever-aging population and rapid development of medical technology. The utilization of interventional pain management has, similarly, shown a continued rise worldwide. This study evaluates the differences in the medical costs in the field of interventional pain treatment (IPT) between two countries: Korea and Japan. Methods: Korean medical insurance costs for 2019 related to pain management focused on IPT were compared to those of Japan. Purchasing power parity (PPP) was used to adjust the exchange rate differences and to compare prices in consideration of the respective societies' economic power. Results: The cost of trigger point injections in Japan was 1.06 times higher than that of Korea, whereas the perineural and intraarticular injection prices were lower in Japan. The cost of epidural blocks was higher in Japan compared to Korea in both cervical/thoracic and lumbar regions. As for blocks of peripheral branches of spinal nerves, the cost of scapular nerve blocks in Japan was lower than that in Korea, given a PPP ratio 0.09. For nerve blocks in which fluoroscopy guidance is mandatory, the costs of epidurography in Japan were greater than those in Korea, given a PPP ratio 1.04. Conclusions: This is the first comparative study focusing on the medical costs related to IPT between Korea and Japan, which reveals that the costs differed along various categories. Further comparisons reflecting more diverse countries and socio-economic aspects will be required.

An Unexpected Complication Resulting from Radiofrequency Ablation for Treating Facet Joint Syndrome: A Case Report.

Lumbar facet joints have been identified as a potential source of chronic low back pain (LBP) in 15% to 45% of patients, with the prevalence of such pain varying based on specific populations and settings examined. Lumbar facet joint interventions are useful in the diagnosis as well as the therapeutic management of chronic LBP. Radiofrequency ablation (RFA) of medial branch nerves is recognized as a safe and effective therapy for chronic facet joint pain in the lumbosacral spine, and its efficacy has already been established. The use of RFA is currently widespread in the management of spinal pain, but it is noteworthy that there have been works in the literature reporting complications, albeit at a very low frequency. We present a case of third-degree skin burns following radiofrequency ablation (RFA) for the management of facet joint syndrome. Postoperatively, the patient's skin encircling the needle displayed a pallor and exhibited deterioration in conjunction with the anatomical anomaly. The affected area required approximately 5 months to heal completely. During RFA, heat can induce burns not only at the point of contact with the RF electrode but also along the length of the needle. Vigilant attention is necessary to ensure patient safety and to address any potential complications that may arise during the procedure, including the possibility of minor technical errors.

Effects of Gestational and Lactational Lead Exposure and High Fat Diet Feeding on Cerebellar Development of Postnatal Rat Offspring.

Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.

The current status of fibromyalgia in Korea: an electronic population health data study in Korea.

Background: Fibromyalgia (FM) is a complex disorder characterized by widespread chronic pain and tenderness in the muscles, ligaments, and soft tissues. It is a chronic pain condition often accompanied by other symptoms and comorbidities. To effectively manage FM, it is crucial to obtain fundamental epidemiological data pertaining to the target population. Therefore, this study was conducted to elucidate the epidemiological characteristics of FM in the Korean population. Methods: Population-based medical data of 51,276,314 subscribers to the National Health Insurance Service of Korea from 2014 to 2018 were used in this study. Results: The overall incidence of FM ranged from 441 (2014) to 541 (2018) cases per 100,000 person-years, with a higher prevalence observed among female patients compared to male patients. The incidence gradually increased until middle age, followed by a decrease. The highest incidence rates were observed in the fifth decade of life for females and the sixth decade of life for males. When categorizing the affected parts of the body, the shoulder region was observed to be the most frequently affected. A comparison of the drug prescriptions based on medical specialty showed that antidepressants were the most commonly prescribed medications. The management of FM leads to consistent increases in medical expenses, regional disparities, and variations in prescription patterns across different medical specialties. Conclusions: The findings of this study will not only contribute to the understanding of FM characteristics but also provide a vital foundation for efficient management of FM in Korea.

New insight into the mandibular nerve at the foramen ovale level for percutaneous radiofrequency thermocoagulation.

Background: Percutaneous radiofrequency thermocoagulation (RFTC) has been widely utilized in the management of trigeminal neuralgia. Despite using image guidance, accurate needle positioning into the target area still remains a critical element for achieving a successful outcome. This study was performed to precisely clarify the anatomical information required to ensure that the electrode tip is placed on the sensory component of the mandibular nerve (MN) at the foramen ovale (FO) level. Methods: The study used 50 hemi-half heads from 26 South Korean adult cadavers. Results: The cross-sectioned anterior and posterior divisions of the MN at the FO level could be distinguished based on an irregular boundary and color difference. The anterior division was clearly brighter than the posterior one. The anterior division of the MN at the FO level was located at the whole anterior (38.0%), anteromedial (6.0%), anterior center (8.0%), and anterolateral (22.0%) parts. The posterior division was often located at the whole posterior or posterolateral parts of the MN at the FO level. The anterior divisions covered the whole MN except for the medial half of the posterolateral part in the overwrapped images of the cross-sectional areas of the MN at the FO level. The cross-sectional areas of the anterior divisions were similar in males and females, whereas those of the posterior divisions were significantly larger in males (P = 0.004). Conclusions: The obtained anatomical information is expected to help physicians reduce unwanted side effects after percutaneous RFTC within the FO for the MN.

Coccydynia: anatomic origin and considerations regarding the effectiveness of injections for pain management.

Coccydynia is a debilitating pain disorder. However, its pathophysiology is not well understood. When approaching coccydynia, the exact underlying cause of pain must be identified to develop an appropriate treatment plan. The specific approach to coccydynia can vary depending on an individual's condition and the underlying cause. Thorough evaluation by a pain physician is essential to determine the most appropriate course of treatment. The purpose of this review is to examine the various causes contributing to coccygeal pain and specifically focus on the exact anatomical neurostructures, such as the anococcygeal nerve, perforating cutaneous nerve, and ganglion impar. We also reviewed the relevant clinical outcomes and suggested recommendations for each anatomical structure.

Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus.

Among the animal models of Parkinson's disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.

Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress.

The ability to cope with stress is essential for emotional stability and mental health. It is also hypothesized that factors promoting resilience to stress may offer treatment strategies for maladaptive disorders such as anxiety and depression. Here, we find that physical restraint reduces the expression of type 1 adenylyl cyclase (Adcy1), a neurospecific synaptic enzyme that positively regulates the cAMP signaling cascade. Conversely, an increase of forebrain Adcy1 expression in transgenic mouse (i.e., Adcy1 tg mouse) predisposes individuals to molecular stability and behavioral resilience. Transgenic overexpression of Adcy1 prevents the physical restraint-induced down-regulation of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Further, Adcy1 tg mice maintain regular locomotive activity in novelty exploration and voluntary wheel running following physical restraint. Adcy1 tg mice show higher corticosterone and lower basal glucocorticoid receptor (GR) expression, along with a higher MR (mineralocorticoid receptor) to GR ratio in the hippocampus. Further, Adcy1 tg mice show reduced immobility under acute physical stress conditions in the forced swimming test and are more sensitive to the antidepressant desipramine. Our results demonstrate a novel function of Adcy1 in stress coping and suggest Adcy1 as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.

Facet joint injections for management of low back pain: a clinically focused review.

Lumbar facet joints have been implicated in chronic low back pain in up to 45% of patients with low back pain (LBP). Facet joint pain diagnosis and management are always challenging for pain physicians. Facet joint pain is not diagnosed by specific demographic features, pain characteristics, or physical findings, even though electrodiagnostic studies and imaging modalities are available. Although comparative local anesthetics or placebo saline injections can be used, diagnostic blocks are the only reliable diagnostic measures according to the current literature. Treatment of chronic LBP arising due to facet joint includes intraarticular injections, medial branch blocks, and radiofrequency neurotomy. However, the evidence of their clinical efficacy is continuously under scrutiny. Pain physicians must have a detailed understanding of the spinal anatomy in order to perform safe and effective interventional procedures. This review outlines the important aspects of spinal anatomy as they relate to interventional pain management related to facet joint injections. Additionally, we provide a comprehensive review of the procedure and clinical evidence.

New insights into pathways of the accessory nerve and transverse cervical artery for distal selective accessory nerve blockade.

BACKGROUND: The aim of this study was to clarify the topographical relationship between the accessory nerve (AN) and transverse cervical artery (TCA) to provide safe and convenient injection points for AN blockade. METHODS: This study included 21 and 30 shoulders of 14 embalmed Korean adult cadavers and 15 patients, respectively, for dissection and ultrasound (US) examination. RESULTS: The courses of the TCA and AN in the scapular region were classified into four types based on their positional relationships. Type A indicated the nerve that was medial to the artery and ran parallel without changing its location (38%). In type B (38%), the nerve was lateral to the artery and ran parallel without changing its location. In type C (19%), the nerve or artery traversed each other only once during the whole course. In type D (5%), the nerve or artery traversed each other more than twice forming a twist. At the levels of lines I-IV, the nerve was relatively close to the artery (approximately 10 mm). TCAs were observed in all specimens around the superior angle of the scapula at the level of line II, whereas they were not found below line VI. In US images of the patients, the TCA was commonly observed at the level of line II (93.3%) where all ANs and TCAs were observed in cadaveric dissection. CONCLUSIONS: The results expand the current knowledge of the relation between the AN and TCA, and provide helpful information for selective diagnostic nerve blocks in the scapular region.

Distribution patterns of the cutaneous nerves on the dorsum of the foot and their clinical significance.

The aim of this study was to clarify the distribution patterns of the cutaneous nerves on the dorsum of the foot. This study investigated 130 feet of 77 cadavers. The distribution patterns of the sural (SN) and deep fibular nerves (DFN) were classified into five and four types, respectively. In Type A, the SN was only distributed to the lateral side of the fifth toe. In Type B, the nerve was distributed to the medial side of the fourth toe and both sides of the fifth toe. In Type C, the nerve was mainly distributed to the lateral side of the fifth toe. In Type D, the nerve was distributed to the lateral side of the third toe and both sides of the fourth and fifth toes. In Type E, no SN was found. In Type α, the DFN was simultaneously distributed to the lateral side of the first toe and the medial side of the second toe. In Type ß, the nerve was distributed like in Type α and additionally to the medial side of the first toe. In Type γ, the nerve was distributed like in Type α and additionally to the lateral side of the second toe and the medial side of the third toe. In Type δ, no DFN was found. The results of this study will help physicians to reduce the incidence of iatrogenic nerve injury and improve the quality of diagnoses of relevant nerves in this body region. Clin. Anat. 33:592-597, 2020. © 2019 Wiley Periodicals, Inc.

New insights into pathways of the dorsal scapular nerve and artery for selective dorsal scapular nerve blockade.

BACKGROUND: The aim of this study was to clarify the topographical relationships between the dorsal scapular nerve (DSN) and the dorsal scapular artery (DSA) in the interscapular region to identify safe and convenient injection points related to DSN blockade. METHODS: Thirty shoulders of embalmed Korean cadavers and 50 live subjects were used for dissection and ultrasound (US) analysis. RESULTS: The running patterns of the DSA and DSN in the interscapular region were classified into 3 types. Type I was defined as nerves that were medial to the artery and parallel without changing location (80.0% of specimens). In type II (13.3%), the nerve and artery traversed one another only one time over their entire length. In type III (6.7%), the nerve and artery traversed one another, resembling a twist. Above the level of the scapular spine, the nerve was always medial to the artery. Below the scapular spine, the number of arteries was obviously decreased. Most of the arteries were lateral to the medial border of the scapula, except at the level of the superior angle of the scapula artery (SA). The positional tendency of the DSN toward the medial or lateral sides from the medial border of the scapula was similar. In US imaging of live subjects, the DSA was most observed at the level of the SA (94.0%). CONCLUSIONS: Results of this study enhance the current knowledge regarding the pathway of the DSN and DSA and provide helpful information for selective diagnostic nerve blocks in the interscapular region.

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression.

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages. To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments, adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation. Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation. We also detected the expression levels of neurogenic cell markers (doublecortin) and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor. Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. Sodium butyrate pretreatment reversed these changes. These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences (approval No. KIRAMS16-0002) on December 30, 2016.

Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation.

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.

Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration.

Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is commonly associated with excitotoxicity, oxidative stress, and neuroinflammation. The pathological process of neurotoxicity induces neuronal death, interrupts synaptic plasticity in the brain, and is similar to that of diverse neurodegenerative diseases. Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes. Specifically, brain-derived neurotropic factor (BDNF) and gamma-aminobutyric acid (GABA)-ergic transmission are related to both neurodegeneration and neuroregeneration. This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission, their underlying mechanisms, and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration. This review will provide a comprehensive overview of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.

Changes in epigenetic markers, DNMT1 and HDAC1/2, in the adult mouse hippocampus after cranial irradiation.

Brain exposure to ionizing radiation can cause functional deficits in the hippocampus, including memory impairment. However, the specific molecular mechanisms underlying irradiation-induced cognitive impairments are largely unknown. Changes in DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which are involved in DNA methylation and histone remodeling, may be associated with behavioral changes in learning and memory. We assessed changes in the levels of enzymes associated with the epigenetic modification of gene expression, including DNMT1, HDAC1, HDAC2, Sirtuin 1 (SIRT1), and acetylated histone H3 (Ace-H3) in the mouse hippocampus 1 and 30days after a single exposure to cranial irradiation (0 or 10Gy). mRNA levels of HDAC1 were significantly downregulated 1day after irradiation with 10Gy, and those of DNMT1, HDAC1, and HDAC2 were significantly downregulated 30days post-irradiation. Western blot analysis revealed significant decreases in DNMT1, HDAC1, and HDAC2 protein levels 1 and 30days after irradiation with 10Gy. Furthermore, protein levels of SIRT1 and Ace-H3 were significantly downregulated in the mouse hippocampus 1 and 30days after cranial irradiation. Our findings suggest that the reduction in epigenetic gene expression is associated with hippocampal dysfunction in mice exposed to cranial irradiation.

Ethanolic extract of Schizonepeta tenuifolia attenuates osteoclast formation and activation in vitro and protects against lipopolysaccharide-induced bone loss in vivo.

BACKGROUND: Excessive osteoclast activity is a major cause of metabolic bone disorders, such as osteopenia, rheumatoid arthritis, and osteoporosis. Thus, discovery of agents targeting osteoclast differentiation and bone resorption is important for development of novel treatments for bone diseases. It has been demonstrated that ethanolic extract of schizonepeta tenuifolia (EEST) has potent anti-oxidant and anti-inflammatory activities. However, the beneficial effects of EEST on bone metabolism have not been studied. Therefore, we intend to investigate the effects of EEST on osteoclast differentiation. METHODS: We examined the effects and mechanisms of action of the EEST on osteoclastogenesis in vitro in bone marrow macrophages (BMMs) stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL) and in vivo using a mouse model of lipopolysaccharide (LPS)-induced bone destruction. RESULTS: We found that EEST inhibited phosphorylation of Akt and IkB at early stages of RANKL-induced osteoclastogenesis. Furthermore, EEST negatively controlled the transcription and translation levels of nuclear factor of activated T cells c1 (NFATc1) and the translation level of c-Fos at the final stage of osteoclast differentiation. Reflecting these effects, EEST blocked both filamentous actin (F-actin) ring formation and bone resorbing activity of mature osteoclasts in vitro. The inhibitory effects of EEST on osteoclast formation and activity were observed in an LPS-mediated bone erosion mouse model using micro-CT and histological analysis. CONCLUSIONS: EEST is a potential agent that is able to treat osteoclast-related bone diseases, such as osteoporosis.

Trimethyltin-induced hippocampal neurodegeneration: A mechanism-based review.

Trimethyltin (TMT), a toxic organotin compound, induces neurodegeneration selectively involving the limbic system and especially prominent in the hippocampus. Neurodegeneration-associated behavioral abnormalities, such as hyperactivity, aggression, cognitive deficits, and epileptic seizures, occur in both exposed humans and experimental animal models. Previously, TMT had been used generally in industry and agriculture, but the use of TMT has been limited because of its dangers to people. TMT has also been used to make a promising in vivo rodent model of neurodegeneration because of its region-specific characteristics. Several studies have demonstrated that TMT-treated animal models of epileptic seizures can be used as tools for researching hippocampus-specific neurotoxicity as well as the molecular mechanisms leading to hippocampal neurodegeneration. This review summarizes the in vivo and in vitro underlying mechanisms of TMT-induced hippocampal neurodegeneration (oxidative stress, inflammatory responses, and neuronal death/survival). Thus, the present review may be helpful to provide general insights into TMT-induced neurodegeneration and approaches to therapeutic interventions for neurodegenerative diseases, including temporal lobe epilepsy.