A5041215838- Pain Mechanisms and Treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Pain Management and Placebo Effect
- Neuropeptides and Animal Physiology
- Sphingolipid Metabolism and Signaling
- Pharmacological Effects of Natural Compounds
- Exercise and Physiological Responses
- Hereditary Neurological Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Musculoskeletal pain and rehabilitation
- Long-Term Effects of COVID-19
- Biochemical effects in animals
- Cancer, Stress, Anesthesia, and Immune Response
- Hormonal and reproductive studies
- Veterinary Pharmacology and Anesthesia
- Alkaloids: synthesis and pharmacology
- Ion channel regulation and function
- Adipose Tissue and Metabolism
- Calpain Protease Function and Regulation
- Tryptophan and brain disorders
- Neuroscience, Education and Cognitive Function
- Nicotinic Acetylcholine Receptors Study
- Vagus Nerve Stimulation Research
- Pediatric Pain Management Techniques
- Hydrogen's biological and therapeutic effects
RIKEN Center for Biosystems Dynamics Research
2020-2025
Kyoto University
2023-2025
Nagasaki University
2017-2023
Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the neurobiological basis remains unclear. In this study, we found that μ-opioid signals in medial prefrontal cortex (mPFC) activate descending pain inhibitory system to initiate placebo neuropathic rats. Chemogenetic manipulation demonstrated specific activation of receptor–positive (MOR + ) neurons mPFC or suppression mPFC–ventrolateral periaqueductal gray (vlPAG) circuit...
Despite the recognized roles of neuroinflammation in mental illnesses, PET imaging on currently available biomarkers has limitations due to lack evidence demonstrating their relationship molecular and cellular events inflammation associated with pathology illness. Rodent stress models, such as chronic social defeat (SDS), have identified crucial for COX-1 TLR4, which are innate immune molecules, SDS-induced its behavioral consequences. In this study, we performed TLR4 at multiple time points...
Abstract We have previously demonstrated that lysophosphatidic acid (LPA) plays key roles in the initial mechanisms for neuropathic pain (NeuP) development. Here, we examined whether LPA receptor and production are related to glial activation at a late stage after partial sciatic nerve ligation (pSNL) by use of microglial inhibitor, Mac1-saporin or astrocyte l -α-aminoadipate ( -AA). Although single intrathecal injection 1/3 antagonist, Ki-16425 did not affect threshold day 7 spinal cord...
We developed a mouse model for central post-stroke pain (CPSP), centrally-originated neuropathic (NeuP). In this mode, mice were first injected with Rose Bengal, followed by photo-irradiation of left middle cerebral artery (MCA) to generate thrombosis. Although the MCA thrombosis was soon dissolved, reduced blood flow remained more than 24 h due subsequent occlusion microvessels. This photochemically induced (PIT) showed hypersensitivity electrical stimulation both sides paw, but did not...
Treatment for fibromyalgia is an unmet medical need and its pathogenesis still poorly understood. The present study demonstrated that intermittent psychological stress (IPS), or empathy causes generalized chronic abnormal pain with female predominance. persistence of the phenotype was dependent on unpredictability stressor. reversed by pregabalin (PGB), duloxetine (DLX) mirtazapine (Mir), but not diclofenac morphine. Differential administration these existing medicines revealed sites PGB Mir...
Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through alternation pain-related genes/proteins expression demyelination. However, LPA its brain are still poorly understood. In present study, we revealed that LPA5 corpus callosum elevated after demyelination, hyperalgesia Aδ-fibers following cuprizone-induced demyelination was mediated by signaling. These data suggest may key mechanisms underlying brain.
We have developed an experimental fibromyalgia-like mouse model using intermittent cold stress (ICS), where chronic pain is generalized, female predominant, and abolished in type 1 lysophosphatidic acid receptor-knockout (LPA<sub>1</sub><sup> -/-</sup>) mice but not reversed by systemic or brain treatment with morphine. investigated two issues the present study: (1) whether mechanisms lack of morphine analgesia are associated ICS (2) what involved analgesia. ICS-induced hyperalgesia was...
Treatment of fibromyalgia is an unmet medical need; however, its pathogenesis still poorly understood. In a series studies, we have demonstrated that some pharmacological treatments reverse generalized chronic pain but do not affect the lack morphine analgesia in intermittent cold stress (ICS)–induced fibromyalgia-like model mice. Here report repeated intraperitoneal with mirtazapine, which presumed to disinhibit 5-hydroxytriptamine (5-HT) release and activate 5-HT1 receptor through...
Lysophosphatidic acid (LPA) signaling is known to play key roles in the initiation and maintenance of various chronic pain models. Here we examined whether LPA also involved diabetes-induced abnormal behaviors. The high-fat diet (HFD) showing elevation blood glucose levels body weight caused thermal, mechanical hyperalgesia, hypersensitivity 2000 or 250 Hz electrical-stimulation hyposensitivity 5 stimulation paw wild-type (WT) mice. These HFD-induced behaviors increase, but not elevated were...
Reactive oxygen species (ROS) are highly reactive and directly attack surrounding biomolecules to deteriorate cellular tissue functions. Meanwhile, ROS also serve as signaling mediators upregulate pro-inflammatory cytokine expression via activation of the nuclear factor kappa B pathway, increased cytokines trigger respiratory burst inflammatory cells that further accelerates production in inflamed tissue. Such crosstalk between responses leads a chain reaction negativity, cause progression...
Pain is an unpleasant subjective experience that usually modified by complex multidimensional neuropsychological processes. Increasing numbers of neuroimaging studies in humans have characterized the hierarchical brain areas forming a pain matrix, which involved different dimensions components. Although mechanistic investigations been performed extensively rodents, homologous regions components not fully understood rodent brain. Herein, we successfully identified several activated response...
Fibromyalgia (FM), a disease of unknown etiology characterized by chronic generalized pain, is partly recapitulated in an animal model induced repeated acid saline injections into the gastrocnemius muscle. Here, we attempted to investigate sex difference pain hypersensitivity (mechanical allodynia and electrical stimulation) saline-induced FM-like (AcGP) model. The first unilateral injection muscle at day 0/D0 second D5 (post 0, P0) transient long-lasting mechanical allodynia, respectively,...
Abstract Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the underlying neurobiological mechanisms remain unclear. We found that μ-opioid signals in medial prefrontal cortex (mPFC) activate descending pain inhibitory system to initiate placebo neuropathic rats. Chemogenetic manipulation demonstrated specific activation of receptor-positive (MOR + ) neurons mPFC or suppression mPFC-ventrolateral periaqueductal gray (vlPAG) circuit...
The intermittent cold stress-induced generalized pain response mimics the pathophysiological and pharmacotherapeutic features reported for fibromyalgia patients, including presence of chronic female dominance. In addition, is abolished in lysophosphatidic acid receptor type-1 knockout mice, as many cases neuropathic models. This study aimed to identify brain loci involved stress test their dependence on type-1. Positron emission tomography analyses using 2-deoxy-2-[18 F]fluoro-d-glucose a...
A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context various infections, such as COVID-19. Although pathogenic mechanisms underlying an infection causing fever pain well established, fatigue induced by specific brain regions remain unclear. To elucidate whether how peripheral cause via regional neuroinflammation, we performed a brain-wide investigation neuroinflammation pseudoinfection rat model using [18F]DPA-714...
Fibromyalgia, a representative central and generalized pain is known to comprise an approximately 2% population ratio in developed countries. patients are less responsive classic commonly used analgesic regimens, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids. Here we animal model showing chronic with female predominant sex difference, similar clinical features of fibromyalgia clinic, by exposing mice intermittent psychological stress (IPS), seeing, smelling listening...
Kyotorphin (L-Tyrosine-L-Arginine) is an opioid-like analgesic dipeptide, which was isolated from bovine brain. Regarding the mechanisms underlying centrally administered kyotorphin-induced analgesia, we have proposed that met-enkephalin release one of (Nature 1979). The previous studies revealed kyotorphin binds to putative specific Gi-coupled receptor, and Leucine-Arginine (LR) a antagonist (JBC, We also found N-methyl derivatives (NMYR) LR (NMLR) are potent stable agonist antagonist,...
We developed the fibromyalgia-like chronic pain model in mice by using intermittent cold stress. This mouse was found to have similarity fibromyalgia patients terms of pathophysiology and pharmacotherapy, which includes loss sensitivity morphine. Based on speculation that excess amounts endogenous opioids induced repeated stress may cause a type opioid analgesic tolerance, we attempted use anti-opioid NMDA receptor (NR2A subunit)-deficient see recovery morphine analgesia. ICS-treated NR2A-KO...