- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Ion Channels and Receptors
- Oral health in cancer treatment
- Ion channel regulation and function
- Pharmacological Effects of Natural Compounds
- Pharmacological Receptor Mechanisms and Effects
- Neuroendocrine regulation and behavior
- Head and Neck Cancer Studies
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Plant-based Medicinal Research
- Nerve injury and regeneration
- Complementary and Alternative Medicine Studies
- Neurobiology and Insect Physiology Research
- Adipokines, Inflammation, and Metabolic Diseases
- Pharmacogenetics and Drug Metabolism
- Oral Health Pathology and Treatment
- Ginseng Biological Effects and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroinflammation and Neurodegeneration Mechanisms
- Gastrointestinal motility and disorders
- Botulinum Toxin and Related Neurological Disorders
Juntendo University
2022-2025
Jikei University School of Medicine
2021-2025
National Cancer Research Institute
2012-2025
Tokyo National Hospital
2023-2024
NTL Institute for Applied Behavioral Science
2021
Japan Agency for Medical Research and Development
2017
Jichi Medical University
2015
Hiroshima University
2006-2010
Tottori University
2006-2008
Microglia perform both neuroprotective and neurotoxic functions in the brain, with this depending on their state of activation release mediators. Upon P2X(7) receptor stimulation, for example, microglia small amounts TNF, which protect neurons, whereas LPS causes massive TNF leading to neuroinflammation. Here we report that, rat primary cultured microglia, nicotine enhances receptor-mediated release, whilst suppressing LPS-induced but without affecting mRNA expression via alpha7 nicotinic...
Objective. Chemotherapy-induced oral mucositis (COM) is characterized by painful inflammation with prolonged damage that involves the pathological pain-evoking prostaglandin E2 (PGE2). We previously found gargling hangeshashinto (HST), a traditional Japanese medicine, was effective for treatment of COM. However, little known regarding mechanisms. Our aim to identify active ingredients and clarify characteristic effects HST on PGE2 system. Methods. Prostanoids produced human keratinocytes...
Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert analgesic effect both humans animals, the results of certain animal experiments have shown partially blocked by opioid receptor antagonists. To investigate relationship between μ (MOR), we evaluated how affects MOR vitro performing electrical impedance-based biosensor assay (CellKey™ assay), intracellular cAMP assay,...
Abstract We investigated whether angiotensin (ANG) II and its receptors contribute to lipopolysaccharide (LPS)‐induced microglial activation through of the proinflammatory transcription factors nuclear factor κB (NF‐κB) activator protein‐1 (AP‐1). Using primary cell cultures, we examined losartan [ANG type 1 receptor (AT ) antagonist] alters effects LPS on: production interleukin‐1 (IL‐1) nitric oxide, morphology, NF‐κB AP‐1 activities. Reverse transcription‐polymerase chain reaction...
Various colonic motor activities are thought to mediate propulsion and mixing/absorption of content. The Japanese traditional medicine daikenchuto (TU-100), which is widely used for postoperative ileus in Japan, accelerates emptying healthy humans. Hydroxy-α sanshool (HAS), a readily absorbable active ingredient TU-100 KCNK3/KCNK9/KCNK18 blocker as well TRPV1/TRPA1 agonist, has been investigated its effects on motility. Motility was evaluated by intraluminal pressure video imaging rat...
Cancer cachexia (CC) is a multifactorial disease characterized by decreased food intake and loss of body weight due to reduced musculature with or without fat mass. Patients gastric cancer have high incidence cachexia. We previously established novel CC rat model induced human cancer-derived 85As2 cells in order examine the pathophysiology identify potential therapeutics. In patients CC, anorexia often observed, despite elevation ghrelin, suggesting that ghrelin resistance may develop these...
Neuropathic pain resulting from peripheral neuronal damage is largely resistant to treatment with currently available analgesic drugs. Recently, ATP, lysophosphatidic acid, and platelet-activating factor (PAF) have been reported play important inductive roles in neuropathic pain. In the present study, we found that pain-like behaviors partial sciatic nerve ligation (PSL) were attenuated by deficiency of lysophosphatidylcholine acyltransferase (LPCAT)2, which one PAF biosynthetic enzymes. By...
Mesenchymal stem cells (MSCs), which are isolated from adipose tissue (AD-MSCs), umbilical cord (UC-MSCs), or bone marrow, have therapeutic potential including anti-inflammatory and immunomodulatory activities. It was recently reported that MSCs also effective as a treatment for neuropathic pain, although the underlying mechanisms yet to be resolved. Therefore, in this study, we investigated effects of human AD- UC-MSCs on pain its using rat models partial sciatic nerve ligation (PSNL). were...
Abstract Prototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and been considered to be more effective than newer selective serotonin reuptake inhibitors, in treating severe depression. However, the clinical contribution of non-monoaminergic effects TCAs remains elusive. In this study, we discovered that amitriptyline, a typical TCA, directly binds lysophosphatidic acid receptor 1 (LPAR1), G protein-coupled receptor,...
To examine mechanisms underlying substance P (SP) release from primary sensory neurons in response to activation of the non-selective cation channel transient receptor potential ankyrin 1 (TRPA1), SP cultured rat dorsal root ganglion was measured, using radioimmunoassay, by stimulating TRPA1 with allyl isothiocyanate (AITC), a agonist. AITC-evoked occurred concentration- and time-dependent manner. Interestingly, p38 mitogen-activated protein kinase (p38) inhibitor SB203580 significantly...
Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence cachexia, few experimental models for study CC been established. Herein, we developed animal using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from human line MKN-45, 85As2, derived peritoneal...
In Brief many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism after chemotherapy has not been extensively studied. this study, we investigated spontaneous mechanical allodynia a preclinical model of systemic administration drug 5-fluorouracil, using our proprietary assay system for conscious rats. 5-Fluorouracil caused leukopenia but did induce pain-related...
Abstract Background Stimulation of transient receptor potential ankyrin 1 ( TRPA 1), which abundantly expressed in enterochromaffin cells ECC ), has been reported to exert apparently contradictory results vitro contractility and vivo gastrointestinal GI ) transit evaluations. The pharmaceutical‐grade Japanese traditional medicine daikenchuto TU ‐100) be beneficial for postoperative ileus POI accelerate animals humans. ‐100 was recently shown increase intestinal blood flow via stimulation the...
Abstract Processed Aconiti tuber (PAT) is used to treat pain associated with various disorders. Although it has been demonstrated that the κ opioid receptor (KOR) signaling pathway a mediator of analgesic effect PAT, active components affecting have not yet identified. In this study, we explored candidate PAT by pharmacokinetic analysis and identified ignavine, which different structure from aconitine alkaloids. A binding assay receptors showed ignavine specifically binds μ (MOR), KOR....
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event bone-modifying agents used to prevent bone complications in cancer patients with metastasis. Currently, early treatment only way further progression, as pathogenesis MRONJ has not yet been elucidated, and standard established. The aim this study was identify marker for detection by exploring substances saliva specific at an stage. We collected salivary samples from 17 conducted metabolomic analyses using...
Abstract Background Oral mucositis (OM) associated with cancer treatment not only impairs patients’ quality of life but also causes delays or changes. This prospective exploratory study was conducted to evaluate the efficacy Episil® oral liquid, which is an approved protective formulation for mucosa in patients OM. The extent pain-relieving effect, feeling during use, and adverse events problems were evaluated. Methods In total, 10 Japanese OM receiving chemotherapy, pretreatment therapy...
Abstract Background Prototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and been considered to be more effective than newer selective serotonin reuptake inhibitors (SSRIs), in treating severe depression. However, the clinical contribution of non-monoaminergic effects TCAs remains elusive. Aims & Objectives In this study, we hypothesized that one potential targets is lysophosphatidic acid receptor 1 (LPAR1), a G...
Abstract Background Endothelin-1 (ET-1), known as a vasoconstrictor, induces pain signals through its specific receptor ETA (ETAR). We previously reported that the novel selective ETAR antagonist compound E (provided by Eisai Co., Ltd.) restored ET-1-induced attenuation of morphine-induced analgesia with HEK293 cells stably expressing both and mu opioid (ETAR-MOR cells) mice model (Kuroda et al., 2021). Further, among several opioids including morphine, we found ET-1 almost completely...