Jun Sato

Bio: Jun Sato is an academic researcher from Aichi Medical University. The author has contributed to research in topics: Hyperalgesia & Chronic pain. The author has an hindex of 26, co-authored 80 publications receiving 2497 citations. Previous affiliations of Jun Sato include Nagoya University & Chubu University.

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury

Abstract: The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus

Abstract: Recurrent seizure activity has been shown to induce a variety of permanent structural changes in the brain. Matrix metalloproteinases (MMPs) function to promote neuronal plasticity, primarily through cleavage of extracellular matrix proteins. Here, we investigated the role of MMP-9 in the development of pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with PTZ (40 mg/kg) produced kindled seizure, which was accompanied by enhanced MMP-9 activity and expression in the hippocampus. No change in MMP-9 activity was observed in the hippocampi of mice with generalized tonic seizure following single administration of PTZ (60 mg/kg). MMP-9 colocalized with the neuronal marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the development of kindling and the increased MMP-9 levels in the hippocampus. Marked suppression of kindled seizure progression in response to repeated PTZ treatment was observed in MMP-9(−/−) mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor. Microinjecting the BDNF scavenger TrkB-Fc into the right ventricle before each PTZ treatment significantly suppressed the development of kindling in wild-type mice, whereas no effect was observed in MMP-9(−/−) mice. On the other hand, bilateral injections of pro-BDNF into the hippocampal dentate gyrus significantly enhanced kindling in wild-type mice but not MMP-9(−/−) mice. These findings suggest that MMP-9 is involved in the progression of behavioral phenotypes in kindled mice because of conversion of pro-BDNF to mature BDNF in the hippocampus.

Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease.

Abstract: Background Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. Methods and Findings In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. Conclusions Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various neurodegenerative diseases.

Effects of prostaglandins and other putative chemical intermediaries on the activity of canine testicular polymodal receptors studied in vitro

Abstract: (1) An in vitro testis-superior spermatic nerve preparation was used to evaluate the effects of chemical agents applied in the bathing solution. Both directly evoked discharges and responses to algesic solutions [bradykinin (BK) 9×10−8 M, hypertonic saline 616 mM and high K+ solution 60 mM] of polymodal receptors were studied. (2) Prostaglandin (PG)-E2 (1.4×10−6–1.4×10−5 M) and serotonin (5-HT) (1.1×10−6 to 1.4×10−4 M) had only a weak excitatory effect. However, test responses to algesic substances were regularly greatly increased by PG-E2,-I2 and 5-HT. Concentrations of PG-E2 of 1.4×10−8 M or grealer augmented BK responses; higher concentrations and/or longer applications were needed to enhance responses to algesic salt solutions. Effective concentrations for the PGs and 5-HT were near those reported for inflamed tissues and exudate. (3) Aspirin (ASA) (5.5×10−4 M or greater, for more than 4 min) suppressed the responses to BK but not those evoked by hypertonic saline. The ASA effect on the BK response was largely restored by an addition of PG-E2. (4) Substance P also had a weak excitatory effect on some polymodal receptors, but no significant enhancement of the response to BK was noted. (5) These results further support a role of polymodal receptors in transmitting nociceptive information, of inflammatory origin.

Neuroanatomy of the pain system and of the pathways that modulate pain

Abstract: We review many of the recent findings concerning mechanisms and pathways for pain and its modulation, emphasizing sensitization and the modulation of nociceptors and of dorsal horn nociceptive neurons. We describe the organization of several ascending nociceptive pathways, including the spinothalami