Kyushu University Academic Staff Educational and Research Activities Database
List of Presentations
Tomohiro Yamashita Last modified date:2019.06.25

Assistant Professor / Department of Pharmaceutical Health Care and Sciences / Faculty of Pharmaceutical Sciences


Presentations
1. Tomohiro Yamashita,Sawako Kamikaseda,Aya Tanaka,Hidetoshi Tozaki-Saitoh,Makoto Tsuda,Kazuhide Inoue, New pharmacological effects of approved drugs targeting P2X7 receptors against the release of IL-1β from microglial cells and neuropathic pain after peripheral nerve injury, Young Pharmacologist Mixer, 2018.07.
2. Tomohiro Yamashita,Sawako Kamikaseda,Aya Tanaka,Hidetoshi Tozaki-Saitoh,Makoto Tsuda,Kazuhide Inoue, New pharmacological effects of approved drugs targeting P2X7 receptors against the release of IL-1β from microglial cells and neuropathic pain after peripheral nerve injury, WCP2018 KYOTO, 2018.07.
3. Tomohiro Yamashita, Microglial ATP receptors in neuropathic pain, PURINES 2018, 2018.06, Neuropathic pain is a debilitating pain state, which is often caused by peripheral nerve injury (PNI) by autoimmune disease, diabetes, cancer or physical injury. The hallmark symptom of neuropathic pain is tactile allodynia (pain hypersensitivity to innocuous light touching). Tactile allodynia is refractory to available medicines such as non-steroidal anti-inflammatory drugs and opioids. The mechanism of the neuropathic pain was still largely unknown. We found that activated spinal microglia of dorsal horn over-expressed P2X4 receptors(P2X4R)which cause to release brain-derived neurotrophic factor (BDNF) after the stimulation of ATP. BDNF evokes a collapse of their transmembrane anion gradient in the secondary neurons of dorsal hone resulting in tactile allodynia (Tsuda et al. Nature 424, 778-783, 2003; Coull et al. Nature, 438, 1017-1021, 2005). Now we know that various molecules in microglia play important roles in the relation to the neuropathic pain. We examined what regulates the expression of these molecules and found that the transcription factor interferon-regulatory factor 8 (IRF8) is a critical regulator of the gene expression of these molecules in microglia. Recently, we also have found the important role of IRF5-IRF8 for the expression of P2X4R in microglia (Masuda et al. Nat Commun.5:3771, 2014). ATP is released from primary afferent neurons of spinal dorsal horn (SDH) and various glia cells. We found that not microglia nor astrocytes but SDH inhibitory interneurons that express vesicular nucleotide transporter (VNUT) are a candidate source of the ATP (Masuda, et al. Nat. Commun. 7:12529, 2016; Inoue & Tsuda Nature Rev Neurosci, 19, 138-152, 2018).
The role of purinergic P2X4R function in microglia in the mechanisms of neuropathic pain provides exciting insights in its pathogenesis, and suggests P2X4R inhibitors may be potential candidates for new medicines against neuropathic pain. We are finding such inhibitors from already approved medicines as the drug-developing system namely “Eco-Pharma” for providing benefits of science to patients as soon as possible. We will present some examples of Eco-Pharma in the symposium..
4. Tomohiro Yamashita, Makoto Tsuda, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Searching for analgesics targeted at P2X4 receptors by screening of well-established drugs., Purines 2014, 2014.07.