2022/08/11 更新

写真a

ノザキ チヒロ
野崎 千尋
所属
理工学術院 国際理工学センター(理工学術院)
職名
准教授(任期付)
メールアドレス
メールアドレス
プロフィール

ドイツはボン大学にて疾病性疼痛(Pathological pain)に関する研究を行っています⇒日本に帰ってきました。

以前はオピオイド神経系をターゲットにしていましたが、現在はカンナビノイド神経系をターゲットに、以下のテーマを推進しています。

1)内因性カンナビノイドが偏頭痛や薬物乱用頭痛の特徴的な性差を含む病態調節にどのように寄与するか(DFG Eigene Stelleグラントによる助成)
2)カンナビノイドCB2受容体の二面性:CB2活性は様々な神経障害による神経炎症を促進するか抑制するか(BONFORグラントおよび帰国発展研究による助成)

カンナビノイド系は古くから医療利用されてきたわりには、その機序の煩雑さや内因性リガンドの絶対量の少なさからあまり研究が展開されていないところがあります。一方で免疫系および神経系両方へ直接作用するため、免疫―神経のクロストークや神経炎症等に大きく関与すると考えられています。上記の疾病にこだわらず、様々な神経炎症を伴う慢性疾患に対する新たな治療ターゲットとしてカンナビノイド系の関与を掘り下げて行けたらと考えています。

学内研究所等

  • 2020年
    -
    2022年

    理工学術院総合研究所   兼任研究員

学歴

  • 2004年04月
    -
    2007年03月

    星薬科大学大学院   薬学研究科   薬物治療学教室  

  • 2002年04月
    -
    2004年03月

    京都工芸繊維大学大学院   工芸科学研究科   高分子機能工学専攻  

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    京都工芸繊維大学   繊維学部   高分子学科  

学位

  • 星薬科大学   博士

経歴

  • 2020年04月
    -
    継続中

    早稲田大学   理工学術院   准教授

  • 2019年12月
    -
    2020年03月

    東京理科大学生命医科学研究所   炎症・免疫難病制御部門   プロジェクト研究員

  • 2016年01月
    -
    2019年11月

    ドイツ国立ボン大学   Institute of Molecular Psychiatry   DFG Eigene Stelle(チームリーダー)

  • 2011年10月
    -
    2015年12月

    ドイツ国立ボン大学   Institute of Molecular Psychiatry   博士研究員

  • 2007年07月
    -
    2011年09月

    Institut de génétique et de biologie moléculaire et cellulaire (IGBMC)   Medecine translationnelle & Neurogenetique   博士研究員

  • 2006年04月
    -
    2006年10月

    Aalborg University   Center for Sensory-Motor Interaction   リサーチアシスタント

▼全件表示

所属学協会

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    国際カンナビノイド研究学会

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    北米神経科学学会

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    ドイツ神経科学会

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    日本薬理学会

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    国際麻薬会議

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    国際疼痛学会

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研究分野

  • 神経科学一般

  • 薬理学

  • 神経科学一般

  • 薬理学

  • 神経科学一般

研究キーワード

  • 糖尿病

  • 炎症

  • レプチン

  • 肥満

  • 代謝性疾患

  • 神経障害

  • 頭痛

  • 薬物

  • 薬理学

  • 偏頭痛

  • カンナビノイド

  • オピオイド

  • 疼痛

▼全件表示

論文

  • Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice.

    Kosuke Kataoka, Andras Bilkei-Gorzo, Chihiro Nozaki, Akinobu Togo, Keiichiro Nakamura, Keisuke Ohta, Andreas Zimmer, Toru Asahi

    Brain research bulletin   160   40 - 49  2020年07月  [国際誌]

     概要を見る

    Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging. The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions. However, the underlying mechanisms that link CB1 activity and memory decline remain unknown. Mitochondrial activity profoundly influences neuronal function, and age-dependent mitochondrial activity change is one of the known hallmarks of brain aging. As CB1 receptor is expressed on mitochondria and may regulate neuronal energy metabolism in hippocampus, we hypothesized that CB1 receptors might influence mitochondria in hippocampal neurons. Here, we found that CB1 receptor significantly affected mitochondrial autophagy (mitophagy) and morphology in an age-dependent manner. Serine 65-phosphorylated ubiquitin, a key marker for mitophagy, was reduced in adult CB1-deficient mice (CB1-KO) compared to those in wild type controls, particularly in CA1 pyramidal cell layer. Transmission electron microscopy (TEM) analysis showed reduced mitophagy-like events in hippocampus of adult CB1-KO. TEM analysis also showed that mitochondrial morphology in adult CB1-KO mice was altered shown by an increase in thin and elongated mitochondria in hippocampal neurons. 3D reconstruction of mitochondrial morphology after scanning electron microscopy additionally revealed an enhanced density of interconnected mitochondria. Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging. These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory.

    DOI PubMed

  • CB2 receptor deletion on myeloid cells enhanced mechanical allodynia in a mouse model of neuropathic pain.

    Elisa Nent, Chihiro Nozaki, Anne-Caroline Schmöle, David Otte, Andreas Zimmer

    Scientific reports   9 ( 1 ) 7468 - 7468  2019年05月  [国際誌]

     概要を見る

    Neuropathic pain can develop after nerve injury, leading to a chronic condition with spontaneous pain and hyperalgesia. Pain is typically restricted to the side of the injured nerve, but may occasionally spread to the contralateral side, a condition that is often referred to as mirror-image pain. Mechanisms leading to mirror-image pain are not completely understood, but cannabinoid CB2 receptors have been implicated. In this study, we use genetic mouse models to address the question if CB2 receptors on neurons or on microglia/macrophages are involved. First, we show that a GFP reporter protein under control of the CB2 promoter is induced upon partial sciatic nerve ligation in spinal cord, dorsal root ganglia, and highest in sciatic nerve macrophages, but not in neurons. Mice which lack CB2 receptors specifically on myeloid cells (microglia, macrophages) developed a mirror-image allodynia [treatment F1,48 = 45.69, p < 0.0001] similar to constitutive CB2 receptor knockout mice [treatment F1,70 = 92.41, p < 0.0001]. Such a phenotype was not observed after the deletion of CB2 from neurons [treatment F1,70 = 0.1315, p = 0.7180]. This behavioral pain phenotype was accompanied by an increased staining of microglia in the dorsal horn of the spinal cord, as evidenced by an enhanced Iba 1 expression [CB2KO, p = 0.0175; CB2-LysM, p = 0.0425]. Similarly, myeloid-selective knockouts showed an increased expression of the leptin receptor in the injured ipsilateral sciatic nerve, thus further supporting the notion that leptin signaling contributes to the increased neuropathic pain responses of CB2 receptor knockout mice. We conclude that CB2 receptors on microglia and macrophages, but not on neurons, modulate neuropathic pain responses.

    DOI PubMed

  • Involvement of leptin signaling in the development of cannabinoid CB2 receptor-dependent mirror image pain.

    Chihiro Nozaki, Elisa Nent, Andras Bilkei-Gorzo, Andreas Zimmer

    Scientific reports   8 ( 1 ) 10827 - 10827  2018年07月  [査読有り]  [国際誌]

     概要を見る

    Neuropathic pain typically appears in a region innervated by an injured or diseased nerve and, in some instances, also on the contralateral side. This so-called mirror image pain is often observed in mice lacking CB2 receptors after sciatic nerve injury, but the underlying mechanisms for this phenotype largely remain unclear. Here we focused on peripheral leptin signaling, which modulates neuropathic pain development and interacts with the endocannabinoid system. Leptin production is induced at the site of nerve injury in CB2-deficient mice (CB2-KO) mice and wild type controls (WT). However, induction of leptin receptor expression was only observed in the injured nerve of CB2-KO mice. This was paralleled by a stimulation of the leptin receptor-downstream STAT3 signaling and an infiltration of F4/80-positive macrophages. Interestingly, an upregulation of leptin receptor expression STAT3 activity and macrophage infiltration was also observed on the non-injured nerve of CB2-KO mice thus reflecting the mirror image pain in CB2-KO animals. Importantly, perineurally-administered leptin-neutralizing antibodies reduced mechanical hyperalgesia, blocked mirror image pain and inhibited the recruitment of F4/80-positive macrophages. These results identify peripheral leptin signaling as an important modulator of CB2 signaling in neuropathic pain.

    DOI PubMed

  • Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice.

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology   25 ( 8 ) 1388 - 96  2015年08月  [査読有り]  [国際誌]

     概要を見る

    There is evidence to suggest that a dysregulation of endocannabinoid signaling may contribute to the etiology and pathophysiology of migraine. Thus, patients suffering from chronic migraine or medication overuse headache showed alterations in the activity of the arachidonoylethanolamide (AEA) degrading enzyme fatty acid amide hydrolase (FAAH) and a specific AEA membrane transporter, alongside with changes in AEA levels. The precise role of different endocannabinoid system components is, however, not clear. We have therefore investigated mice with a genetic deletion of the two main cannabinoid receptors CB1 and CB2, or the main endocannabinoid degrading enzymes, FAAH and monoacylglycerol lipase (MAGL), which degrades 2-arachidonoylglycerol (2-AG), in a nitroglycerine-induced animal model of migraine. We found that nitroglycerin-induced mechanical allodynia and neuronal activation of the trigeminal nucleus were completely abolished in FAAH-deficient mice. To validate these results, we used two structurally different FAAH inhibitors, URB597 and PF3945. Both inhibitors also dose-dependently blocked nitroglycerin-induced hyperalgesia and the activation of trigeminal neurons. The effects of the genetic deletion of pharmacological blockade of FAAH are mediated by CB1 receptors, because they were completely disrupted with the CB1 antagonist rimonabant. These results identify FAAH as a target for migraine pharmacotherapy.

    DOI PubMed

  • In vivo properties of KNT-127, a novel δ opioid receptor agonist: receptor internalization, antihyperalgesia and antidepressant effects in mice.

    Nozaki C, Nagase H, Nemoto T, Matifas A, Kieffer BL, Gaveriaux-Ruff C

    British journal of pharmacology   171 ( 23 ) 5376 - 5386  2014年12月  [査読有り]

    DOI PubMed

  • δ-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization.

    Nozaki C, Le Bourdonnec B, Reiss D, Windh RT, Little PJ, Dolle RE, Kieffer BL, Gavériaux-Ruff C

    The Journal of pharmacology and experimental therapeutics   342 ( 3 ) 799 - 807  2012年09月  [査読有り]  [国際誌]

    DOI PubMed J-GLOBAL

  • The delta opioid receptor: an evolving target for the treatment of brain disorders.

    Amynah A Pradhan, Katia Befort, Chihiro Nozaki, Claire Gavériaux-Ruff, Brigitte L Kieffer

    Trends in pharmacological sciences   32 ( 10 ) 581 - 90  2011年10月  [査読有り]  [国際誌]

     概要を見る

    Compared to the better-known mu opioid receptor, delta opioid receptors have been relatively understudied. However, the development of highly selective delta opioid agonists and the availability of genetic mouse models have extended our knowledge of delta opioid receptors in vivo. Here we review recent developments in the characterization of delta opioid receptor biology and aspects of delta opioid receptor function that have potential for therapeutic targeting. Preclinical data have confirmed that delta opioid receptor activation reduces persistent pain and improves negative emotional states; clinical trials have been initiated to assess the effectiveness of delta opioid agonists in chronic pain and depression. Furthermore, a possible role for these receptors in neuroprotection is being investigated. The usefulness of targeting delta opioid receptors in drug abuse remains open and a role for these receptors in impulse control disorders is emerging. Finally, the recent demonstration of biased agonism at the delta opioid receptor in vivo opens novel perspectives towards targeting specific therapeutic effects through drug design.

    DOI PubMed J-GLOBAL

  • Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit.

    Chihiro Nozaki, Angela Maria Vergnano, Dominique Filliol, Abdel-Mouttalib Ouagazzal, Anne Le Goff, Stéphanie Carvalho, David Reiss, Claire Gaveriaux-Ruff, Jacques Neyton, Pierre Paoletti, Brigitte L Kieffer

    Nature neuroscience   14 ( 8 ) 1017 - 22  2011年07月  [査読有り]  [国際誌]

     概要を見る

    Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+-NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation.

    DOI PubMed J-GLOBAL

  • Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes opioid analgesia.

    Claire Gaveriaux-Ruff, Chihiro Nozaki, Xavier Nadal, Xavier C Hever, Raphael Weibel, Audrey Matifas, David Reiss, Dominique Filliol, Mohammed A Nassar, John N Wood, Rafael Maldonado, Brigitte L Kieffer

    Pain   152 ( 6 ) 1238 - 1248  2011年06月  [査読有り]  [国際誌]

     概要を見る

    Opioid receptors are major actors in pain control and are broadly distributed throughout the nervous system. A major challenge in pain research is the identification of key opioid receptor populations within nociceptive pathways, which control physiological and pathological pain. In particular, the respective contribution of peripheral vs. central receptors remains unclear, and it has not been addressed by genetic approaches. To investigate the contribution of peripheral delta opioid receptors in pain control, we created conditional knockout mice where delta receptors are deleted specifically in peripheral Na(V)1.8-positive primary nociceptive neurons. Mutant mice showed normal pain responses to acute heat and to mechanical and formalin stimuli. In contrast, mutant animals showed a remarkable increase of mechanical allodynia under both inflammatory pain induced by complete Freund adjuvant and neuropathic pain induced by partial sciatic nerve ligation. In these 2 models, heat hyperalgesia was virtually unchanged. SNC80, a delta agonist administered either systemically (complete Freund adjuvant and sciatic nerve ligation) or into a paw (sciatic nerve ligation), reduced thermal hyperalgesia and mechanical allodynia in control mice. However, these analgesic effects were absent in conditional mutant mice. In conclusion, this study reveals the existence of delta opioid receptor-mediated mechanisms, which operate at the level of Na(V)1.8-positive nociceptive neurons. Delta receptors in these neurons tonically inhibit mechanical hypersensitivity in both inflammatory and neuropathic pain, and they are essential to mediate delta opioid analgesia under conditions of persistent pain. This delta receptor population represents a feasible therapeutic target to alleviate chronic pain while avoiding adverse central effects. The conditional knockout of delta-opioid receptor in primary afferent Na(V)1.8 neurons augmented mechanical allodynia in persistent pain models and abolished delta opioid analgesia in these models.

    DOI PubMed J-GLOBAL

  • Ligand-directed trafficking of the δ-opioid receptor in vivo: two paths toward analgesic tolerance.

    Pradhan AA, Walwyn W, Nozaki C, Filliol D, Erbs E, Matifas A, Evans C, Kieffer BL

    The Journal of neuroscience : the official journal of the Society for Neuroscience   30 ( 49 ) 16459 - 68  2010年12月  [査読有り]  [国際誌]

    DOI PubMed J-GLOBAL

  • Role of cyclin-dependent kinase 5 in capsaicin-induced cough.

    Junzo Kamei, Shun-suke Hayashi, Yoshiki Takahashi, Chihiro Nozaki

    European journal of pharmacology   566 ( 1-3 ) 181 - 4  2007年07月  [査読有り]  [国際誌]

     概要を見る

    The role of cyclin-dependent kinase 5 (Cdk5) in the capsaicin-induced cough reflex was examined in mice. Pretreatment with inhaled roscovitine, a selective Cdk5 inhibitor, at concentrations of 0.3 to 3 mM inhibited the number of capsaicin-induced coughs in a concentration-dependent manner. Pretreatment with inhaled roscovitine, at a concentration of 3 mM also slightly but significantly inhibited the number of citric acid-induced coughs. The number of capsaicin-induced coughs was significantly reduced when C-fibers were desensitized by the pretreatment with capsaicin. The number of citric acid-induced coughs was slightly but significantly reduced in capsaicin-pretreated mice as compared with that in naive mice. Although the inhalation of roscovitine at a concentration of 3 mM significantly reduced the number of citric acid-induced coughs in naive mice to the level observed in capsaicin-pretreated mice, roscovitine had no effect on the number of citric acid-induced coughs in capsaicin-pretreated mice. These results suggest that Cdk5-dependent factors are involved in C-fiber-mediated cough signaling.

    DOI PubMed J-GLOBAL

  • Involvement of mu1-opioid receptor on oxycodone-induced antinociception in diabetic mice.

    Chihiro Nozaki, Junzo Kamei

    European journal of pharmacology   560 ( 2-3 ) 160 - 2  2007年04月  [査読有り]  [国際誌]

     概要を見る

    The effect of naloxonazine, a selective mu(1)-opioid receptor antagonist, on oxycodone-induced antinociception was examined in streptozotocin-induced diabetic mice. Oxycodone (5 mg/kg, s.c.) induced significant antinociception in both non-diabetic and diabetic mice. This antinociceptive effect of oxycodone was completely antagonized by pretreatment with naloxonazine (35 mg/kg, s.c.) in both non-diabetic and diabetic mice. The selective kappa-opioid receptor antagonist nor-binaltorphimine (20 mg/kg, s.c.) also antagonized oxycodone-induced antinociception in diabetic mice, but only had a partial effect in non-diabetic mice. These results suggest that although primarily interacts with mu(1)-opioid receptor, kappa-opioid receptors are also strongly involved in oxycodone-induced antinociception.

    DOI PubMed J-GLOBAL

  • Possible involvement of opioidergic systems in the antinociceptive effect of the selective serotonin reuptake inhibitors in sciatic nerve-injured mice.

    Chihiro Nozaki, Junzo Kamei

    European journal of pharmacology   552 ( 1-3 ) 99 - 104  2006年12月  [査読有り]  [国際誌]

     概要を見る

    The involvement of opioid receptor activation in the antinociceptive effect of either fluvoxamine, a selective serotonin reuptake inhibitor, or serotonin (5-HT) on thermal hyperalgesia and mechanical allodynia in a model of neuropathic pain in mice induced by sciatic nerve ligation was examined. The experiments were conducted 2 or 6 weeks after unilateral sciatic nerve ligation. Ipsilateral thermal hyperalgesia and mechanical allodynia were observed both 2 and 6 weeks after sciatic nerve ligation. Neither s.c. fluvoxamine nor i.t. 5-HT affected sciatic nerve ligation-induced thermal hyperalgesia or mechanical allodynia in mice 2 weeks after sciatic nerve ligation. However, the same dose of either fluvoxamine or 5-HT significantly reduced mechanical allodynia but not thermal hyperalgesia in sciatic nerve ligated mice 6 weeks after surgery. The antinociceptive effect of fluvoxamine on sciatic nerve ligation-induced mechanical allodynia in mice 6 weeks after surgery was completely abolished by pretreatment with either naloxone, a nonselective opioid receptor antagonist, or beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, pretreatment with naltrindole, a selective delta-opioid receptor antagonist, partially but significantly inhibited the antinociceptive effect of fluvoxamine in sciatic nerve ligated mice at the 6th postoperative week. The antinociceptive effect induced by i.t. 5-HT was also completely antagonized by either naloxone or beta-funaltrexamine, and partially inhibited by naltrindole. However, pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no effect against either s.c. fluvoxamine- or i.t. 5-HT-induced antinociception. These results suggest that the antinociceptive effect of s.c. fluvoxamine or i.t. 5-HT in the chronic state of sciatic nerve ligation-induced neuropathic pain may be related to opioidergic activity, mainly through the activation of spinal mu- and delta-opioid receptors.

    DOI PubMed J-GLOBAL

  • Changes in emotional behavior of mice in the hole-board test after olfactory bulbectomy.

    Akiyoshi Saitoh, Noritaka Hirose, Mitsuhiko Yamada, Misa Yamada, Chihiro Nozaki, Takuma Oka, Junzo Kamei

    Journal of pharmacological sciences   102 ( 4 ) 377 - 86  2006年12月  [査読有り]  [国内誌]

     概要を見る

    The most consistent behavioral change caused by olfactory bulbectomy (OBX) is a hyperemotional response to novel environmental stimuli. The aim of this study was to characterize the emotional behavior of OBX mice using the hole-board test. After the olfactory bulbs were lesioned, sham and OBX mice were housed in single cages for 14 days. The number of head-dips in the hole-board test in single-housed OBX mice was significantly greater than that in single-housed sham mice. The head-dipping behaviors in single-housed sham and OBX mice were reversed by treatment with diazepam, a typical benzodiazepine anxiolytic. (+/-)-8-Hydroxy-2-(di-n-propylamino) tetraline hydrobromide (8-OH-DPAT), a selective 5-HT(1A)-receptor agonist that has a non-benzodiazepine anxiolytic-like effect, and (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl benzamide (SNC80), a delta-opioid-receptor agonist, also significantly reversed the number of head-dips in single-housed sham and OBX mice. In conclusion, we suggest that the single-housed OBX mice showed heightened emotional behavior (e.g., increase in head-dipping behavior) in the hole-board test. In addition, we suggest that the hyperemotional behavior characterized by head-dipping behavior in OBX mice was selectively reversed by benzodiazepine and non-benzodiazepine anxiolytics.

    DOI PubMed J-GLOBAL

  • Effect of mexiletine on vincristine-induced painful neuropathy in mice.

    Junzo Kamei, Chihiro Nozaki, Akiyoshi Saitoh

    European journal of pharmacology   536 ( 1-2 ) 123 - 7  2006年04月  [査読有り]  [国際誌]

     概要を見る

    In the present study, we examined the effect of mexiletine on vincristine-induced thermal hyperalgesia in mice. Mice were intraperitoneally treated with vincristine at a dose of 0.05 mg/kg one day after the measurement of the pre-drug latency in the tail-flick test, and then treated with a dose of 0.125 mg/kg twice a week for 6 weeks. In vincristine-treated mice, a significant decrease in tail-flick latency developed at 6 weeks after treatment. Pretreatment with mexiletine, at doses of 3, 10 and 30 mg/kg, i.p., dose-dependently increased the tail-flick latency in vincristine-treated mice. A significant reduction of the tail-flick latency was observed when the tail-flick latency was examined 60 min after i.t. administration of NG-nitro-L-arginine methyl ester (L-NAME, 30 nmol), a nitric oxide synthase (NOS) inhibitor, in naive mice. This L-NAME-induced thermal hyperalgesia was dose-dependently attenuated by pretreatment with mexiletine (10 and 30 mg/kg, i.p.), 10 min before the injection of L-NAME. The duration of nociceptive behavioral response induced by fenvalerate, at a dose of 0.1 microg, i.t., was significantly increased by pretreatment with L-NAME (30 nmol, i.t.). Intrathecal pretreatment with L-arginine (300 pmol) significantly reversed the L-NAME-induced enhancement of fenvalerate-induced nociceptive responses. The present study demonstrates that systemic mexiletine can effectively attenuate vincristine-induced thermal hyperalgesia. Furthermore, these results suggest that blockade of nitric oxide-induced enhancement of nociceptive transmission, in which tetrodotoxin-resistant sodium channels play an important role, may participate in the antinociceptive effect of mexiletine on vincristine-induced thermal hyperalgesia.

    DOI PubMed J-GLOBAL

  • Characterization of the antinociceptive effects of oxycodone in diabetic mice.

    Chihiro Nozaki, Akiyoshi Saitoh, Junzo Kamei

    European journal of pharmacology   535 ( 1-3 ) 145 - 51  2006年03月  [査読有り]  [国際誌]

     概要を見る

    We investigated the antinociceptive efficacy of systemic and centrally injected oxycodone on thermal hyperalgesia in streptozotocin-induced diabetic mice. The antinociceptive response was assessed by recording the latency in the tail-flick test using the radiant heat from a 50-W projection bulb on the tail. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. Oral (p.o.) and i.t., but not i.c.v., administration of oxycodone prolonged the tail-flick latency in diabetic mice to a level that was considerably longer than the baseline latency in non-diabetic mice. However, morphine did not significantly inhibit the tail-flick response in diabetic mice. The antinociceptive effect of either p.o. or i.t. oxycodone in non-diabetic mice, but not in diabetic mice, was antagonized by pretreatment with a selective mu-opioid receptor antagonist, beta-funaltrexamine. In non-diabetic mice, pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine, had no effect on the peak antinociceptive effect of either p.o. or i.t. oxycodone at 30 min after administration, however, it slightly but significantly reduced oxycodone-induced antinociception at 60 and 90 min after administration. On the other hand, pretreatment with nor-binaltorphimine practically abolished the antinociceptive effects of both p.o.- and i.t.-administered oxycodone in diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, had no effects on the antinociceptive effect of oxycodone in either non-diabetic or diabetic mice. These results suggest that the antinociceptive effects of oxycodone may be mediated by spinal kappa-opioid receptors in diabetic mice, whereas it may interact primarily with supraspinal and spinal mu-opioid receptors in non-diabetic mice.

    DOI PubMed J-GLOBAL

  • Antinociceptive effect of oxycodone in diabetic mice.

    Chihiro Nozaki, Akiyoshi Saitoh, Naoya Tamura, Junzo Kamei

    European journal of pharmacology   524 ( 1-3 ) 75 - 9  2005年11月  [査読有り]  [国際誌]

     概要を見る

    The effect of oxycodone on thermal hyperalgesia in streptozotocin-induced diabetic mice was examined. The antinociceptive response was assessed by recording the latency in the tail-flick test using the radiant heat from a 50-W projection bulb on the tail. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. When diabetic mice were treated with oxycodone (5 mg/kg, s.c.), the tail-flick latency in diabetic mice was prolonged to the level considerably longer than the baseline latencies of non-diabetic mice. However, s.c. administration of morphine (5 mg/kg) did not produce a significant inhibition of the tail-flick response in diabetic mice. Oxycodone, at doses of 1.25-5.0 mg/kg administered s.c., produced a dose-dependent increase in the tail-flick latencies in both diabetic and non-diabetic mice. The antinociceptive effect of oxycodone was antagonized by pretreatment with a selective delta-opioid receptor antagonist, beta-funaltrexamine (20 mg/kg, s.c.), in both non-diabetic and diabetic mice. In non-diabetic mice, pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg/kg, s.c.) had no effect on the peak antinociceptive effect of oxycodone observed 30 min after administration, however, it slightly but significantly reduced oxycodone-induced antinociception observed 60 and 90 min after administration. On the other hand, pretreatment with nor-binaltorphimine practically abolished the peak (30 min) and persistent (60 and 90 min) antinociceptive effects of oxycodone in diabetic mice. Naltrindole (35 mg/kg, s.c.), a selective delta-opioid receptor antagonist, had no effects on the antinociceptive effect of oxycodone in both non-diabetic and diabetic mice. These results suggest that the antinociceptive effects of oxycodone may be mediated by mu- and kappa-opioid receptors in diabetic mice, whereas it may interact primarily with mu-opioid receptors in non-diabetic mice.

    DOI PubMed J-GLOBAL

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Misc

  • Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice (vol 25, pg 1388, 2015)

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    EUROPEAN NEUROPSYCHOPHARMACOLOGY   25 ( 11 ) 2186 - 2186  2015年11月

    その他  

    DOI

  • Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes analgesia

    Raphael Weibel, Claire Gaveriaux-Ruff, Chihiro Nozaki, Xavier Nadal, Xavier C. Hever, Audrey Matifas, David Reissl, Dominique Filliol, John N. Wood, Rafael Maldonado, Brigitte L. Kieffer

    PHARMACOLOGICAL REPORTS   63 ( 1 ) 243 - 243  2011年01月

    研究発表ペーパー・要旨(国際会議)  

  • Role of cyclin-dependent kinase 5 (Cdk5) on capsaicin-induced cough reflex

    Shunsuke Hayashi, Junzo Kamei, Yoshiki Takahashi, Chihiro Nozaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   260P - 260P  2007年

    研究発表ペーパー・要旨(国際会議)  

  • Effects of fluvoxamine on allodynia- and anxiety-like behavior induced by sciatic nerve ligation in mice

    T Shimoi, A Saitoh, C Nozaki, N Hirose, J Kamei

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   250P - 250P  2006年

    研究発表ペーパー・要旨(国際会議)  

  • The role of ATP receptor subtypes on the painful diabetic neuropathy in mice

    C Nozaki, J Kamei

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   67P - 67P  2006年

    研究発表ペーパー・要旨(国際会議)  

  • Effect of oxycodone on thermal allodynia in diabetic mice

    C Nozaki, N Tamura, A Saitoh, J Kamei

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   171P - 171P  2005年

    研究発表ペーパー・要旨(国際会議)  

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受賞

  • 平成30年度卓越研究員候補者

    2018年   日本学術振興会  

    受賞者: 野崎 千尋

  • financement de projets impliquant des post-doctorant en France

    2009年   Fondation pour la Recherche Medicale  

    受賞者: 野崎千尋

共同研究・競争的資金等の研究課題

  • 肥満が誘発する慢性炎症に関連する新たな分子・神経・免疫基盤の解明

    日本学術振興会  科学研究費助成事業 国際共同研究加速基金(帰国発展研究)

    研究期間:

    2019年
     
     
     

    野崎 千尋

  • 偏頭痛の病態調節に対する内因性カンナビノイドの関与

    DFG(ドイツ研究振興協会)  Eigene Stelle (Temporary PI)

    研究期間:

    2016年01月
    -
    2018年12月
     

    野崎千尋

  • 肥満と疼痛:レプチンと内因性カンナビノイドの関与

    Bonfor  Fortsetzungsantrag fur Nachwuchsgruppen

    研究期間:

    2013年01月
    -
    2014年12月
     

    野崎千尋

講演・口頭発表等

  • Genetic ablation of CB2 receptors enhances neuropathic pain development via boosted leptin signaling in peripheral nerves.

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    第90回日本薬理学会  

    発表年月: 2017年03月

  • Contribution of endocannabinoid system on NTG-induced acute migraine-like symptoms.

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    国際麻薬会議  

    発表年月: 2016年07月

  • Nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity is enhanced by reduced CB1 receptor activity..

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    第10回欧州神経科学会フォーラム  

    発表年月: 2016年07月

  • Obesity and pain: Is there a link between leptin and endocannabinoid signaling?

    Chihiro Nozaki, Astrid Markert, Andreas Zimmer

    18th BONFOR-Symposium  

    発表年月: 2015年04月

  • Capsaicin-induced pain behavior is modulated in opioid receptors knockouts.

    Chihiro Nozaki, Claire Gaveriaux-Ruff C, David Reiss, Audrey Matifas, Brigitte Kieffer  [招待有り]

    MOLECULAR TARGETS FOR NOVEL PAIN THERAPEUTICS: From basic research to clinical translation  

    発表年月: 2010年09月

  • Capsaicin-induced pain behavior is modulated by opioid receptors.

    Chihiro Nozaki, Claire Gaveriaux-Ruff C, David Reiss, Audrey Matifas, Brigitte Kieffer  [招待有り]

    New Perspectives in Neuroscience: Joint Meeting of Young Italian and Japanese Neuroscientists  

    発表年月: 2010年09月

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特定課題研究

  • 慢性疾患モデル動物の神経組織を元にした高品質な一次神経培養細胞の作成法の樹立

    2021年  

     概要を見る

    これまで困難とされてきた「発達期を抜けたマウスの脳細胞の初代培養方法の確立」を目指し、組織分散装置であるgentleMACSを導入して、1)初代培養に使用できるマウスの週齢および2)得られた細胞の生存期間の検討を行った。まず1)に関して、P7・P50・P110のマウスを用いて比較検討を行ったところ、何れの条件においても軸索の伸長を伴うカスパーゼ陰性神経細胞の存在が認められた。また2)に関して、少なくとも10日間は培養可能であることが確認できた。以上より、gentleMACSを利用することで「発達期を抜けたマウス由来の脳神経細胞」しかも「比較的長期間の培養に耐え得る細胞」を得られることが解った。

  • 片頭痛で認められる性差に対する内因性カンナビノイドの関与

    2020年  

     概要を見る

    新規嘱任でリソースがほぼ何もない状態からのスタートだったのに加え、コロナ禍で思うように実験研究が進められなかったこともあり、ひたすら来年以降の準備に勤しむことになってしまった。しかしこの助成金に加え2019年度末に採択された科研費も併せて、細胞分取装置を始めとする各種実験機材を取り揃えることができ、2021年度からは新たな研究を展開できる見込みである。本年は内藤記念財団の助成金にも挑戦したが不採択だったため、この新たに揃った研究機材でさらに成果を積み上げ、新たな助成金の採択に向けて挑戦して行きたいと考えている。

 

現在担当している科目

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担当経験のある科目(授業)

  • Neurogenesis and Disease

    University of Bonn  

  • Epigenetics

    University of Bonn  

  • Pharmacology of Addiction and Drugs of abuse

    University of Bonn  

  • Opioids and endogenous opioid systems

    University of Bonn