研究内容

慢性ストレス後、人および実験動物において疼痛反応の増強（ストレス性痛覚過敏）が生じることが知られている。しかし、現在まで、そのメカニズムは明らかにされていない。人や動物の脳には、下行性疼痛調節系という神経回路が存在し、脊髄において痛みの伝達をコントロールしている。私たちは、ストレス負荷後の下行性疼痛調節系の機能変化に注目し、頭痛、過敏性腸症候群、慢性関節リウマチ、顎関節症など多くのストレス関連疾患の治療のために、ストレス性痛覚過敏のメカニズム解明を目標としている。さらに、運動による疼痛抑制効果の存在が報告されているため、エクササイズがストレス性痛覚過敏を寛解?予防するメカニズムの解明に迫りたい。心理的要素の関与が大きく罹病期間の長い慢性疼痛に対し、薬物療法には限界があり、エクササイズなどの代替?補助療法の開発と検証が急務といえる。ストレス性痛覚過敏を引き起こすメカニズムが明らかになり、エクササイズの有効性が検証できれば、多くの有痛性ストレス関連疾患の治療法をさらに前進することができると考えている。

Publications (Imbe, H.)

2023

Hiroki Imbe, Hayato Ihara
Mu opioid receptor expressing neurons in the rostral ventromedial medulla are the source of mechanical hypersensitivity induced by repeated restraint stress Brain Research, 1815(2023), 148465

2020

Shimizu S, Nakatani Y, Kurose M, Imbe H, Ikeda N, Takagi R, Yamamura K, Okamoto K.
Modulatory effects of repeated psychophysical stress on masseter muscle nociception in the nucleus raphe magnus of rats. J Oral Sci. 2020 Mar 28;62(2):231-235. doi: 10.2334/josnusd.19-0320. Epub 2020 Mar 19. PMID: 32074544.

Imbe H, Kimura A.
Significance of medial preoptic area among the subcortical and cortical areas that are related to pain regulation in the rats with stress-induced hyperalgesia. Brain Res. 2020 May 15;1735:146758. doi: 10.1016/j.brainres.2020.146758. Epub 2020 Mar 2. PMID: 32135148.

2018

Imbe H, Kimura A.
Increase of histone acetylation in the GABAergic neurons in the rostral ventromedial medulla associated with mechanical hypersensitivity after repeated restraint stress. Brain Res Bull. 2018 Sep;142:394-402. doi: 10.1016/j.brainresbull.2018.09.004. Epub 2018 Sep 15. PMID: 30227234.

Kimura A, Imbe H.
Robust Subthreshold Cross-modal Modulation of Auditory Response by Cutaneous Electrical Stimulation in First- and Higher-order Auditory Thalamic Nuclei.
Neuroscience. 2018 Feb 21;372:161-180. doi: 10.1016/j.neuroscience.2017.12.051. Epub 2018 Jan 6. PubMed PMID: 29309880.

2017

Imbe H, Kimura A.
Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.
Brain Res Bull. 2017 Sep;134:253-261. doi: 10.1016/j.brainresbull.2017.08.013. Epub 2017 Sep 1. PubMed PMID: 28866293.

Kurose M, Imbe H, Nakatani Y, Hasegawa M, Fujii N, Takagi R, Yamamura K, Senba E, Okamoto K.
Bilateral increases in ERK activation at the spinomedullary junction region by acute masseter muscle injury during temporomandibular joint inflammation in the rats.
Exp Brain Res. 2017 Mar;235(3):913-921. doi: 10.1007/s00221-016-4852-9. Epub 2016 Dec 8. PubMed PMID: 27933357.

2016

Imbe H, Kimura A.
Repeated forced swim stress affects the expression of pCREB and ΔFosB and the acetylation of histone H3 in the rostral ventromedial medulla and locus coeruleus.
Brain Res Bull. 2016 Aug 12;127:11-22. doi:10.1016/j.brainresbull.2016.08.007. [Epub ahead of print] PubMed PMID: 27530066.

2015

Imbe H, Kimura A.
Repeated forced swim stress prior to complete Freund's adjuvant injection enhances mechanical hyperalgesia and attenuates the expression of pCREB and ΔFosB and the acetylation of histone H3 in the insular cortex of rat.
Neuroscience. 2015 Aug 20;301:12-25. doi:10.1016/j.neuroscience.2015.05.065. Epub 2015 Jun 3. PubMed PMID: 26047723.

Kimura A, Imbe H.
Anatomically structured burst spiking of thalamic reticular nucleus cells: implications for distinct modulations of sensory processing in lemniscal and non-lemniscal thalamocortical loop circuitries.
Eur J Neurosci. 2015 May;41(10):1276-93. doi:10.1111/ejn.12874. Epub 2015 Mar 25. PubMed PMID:25808293.

2014

Imbe H, Kimura A, Donishi T, Kaneoke Y.
Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.
Neuroscience 2014, 259: 1-11.

2013

Imbe H, Kimura A, Donishi T, Kaneoke Y.
Effects of restraint stress on glial activity in the rostral ventromedial medulla.
Neuroscience 2013, 241: 10-21.

2012

Imbe H, Kimura A, Donishi T, Kaneoke Y.
Chronic restraint stress decreases glial fibrillary acidic protein and glutamate transporter in the periaqueductal gray matter.
Neuroscience 2013, 223: 209-218.

Kimura A, Yokoi I, Imbe H, Donishi T, Kaneoke Y.
Distinctions in burst spiking between thalamic reticular nucleus cells projecting to the dorsal lateral geniculate and lateral posterior nuclei in the anesthetized rat.
Neuroscience 2012, 226: 208-26. doi:10.1016/j.neuroscience.2012.090.016.

Kimura A, Yokoi I, Imbe H, Donishi T, Kaneoke Y.
Auditory thalamic reticular nucleus of the rat: anatomical nodes for modulation of auditory and cross-modal sensory processing in the loop connectivity between the cortex and thalamus.
J Comp Neurol 2012, 520(7): 1457-80.

2011

Imbe H, Senba E, Kimura A, Donishi T, Yokoi I, Kaneoke Y.
Activation of mitogen-activated protein kinase in descending pain modulatory system.
Journal of Signal Transduction 2011, Article ID 468061.

Donishi T, Kimura A, Imbe H, Yokoi I, Kaneoke Y.
Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.
Neuroscience 2011, 174: 200–215.

2010

Imbe H, Okamoto K, Donishi T, Senba E, Kimura A.
Involvement of descending facilitation from the rostral ventromedial medulla in the enhancement of formalin-evoked nocifensive behavior following repeated forced swim stress.
Brain Res 2010, 1329: 103-112.

Kimura A, Imbe H, Donishi T.
Efferent connections of an auditory area in the caudal insular cortex of the rat: anatomical nodes for cortical streams of auditory processing and cross-modal sensory interactions.
Neuroscience 2010, 166: 1140-1157.

2009

Kimura A, Imbe H, Donishi T.
Axonal projections of auditory cells with short and long response latencies in the medical geniculate nucleus: distinct topographies in the connection with the thalamic reticular nucleus.
Eur J Neurosci 2009, 30: 783–799.

Imbe H, Okamoto K, Donishi T, Kawai S, Enoki K, Senba E, Kimura A.
Activation of ERK in the locus coeruleus following acute noxious stimulation.
Brain Res 2009, 1263: 50–57.

2008

Imbe H, Kimura A, Okamoto K, Donishi T, Aikawa F, Senba E, Tamai Y.
Activation of ERK in the rostral ventromedial medulla is involved in hyperalgesia during peripheral inflammation.
Brain Res 2008, 1187: 103–110.

2007

Imbe H, Okamoto K, Aikawa F, Kimura A, Donishi T, Tamai Y, Iwai-Liao Y, Senba E.
Effects of peripheral inflammation on activation of p38 mitogen-activated protein kinase in the rostral ventromedial medulla.
Brain Res 2007, 1134: 131–139.

Kimura A, Imbe H, Donishi T, Tamai Y.
Axonal projections of single auditory neurons in the thalamic reticular nucleus: implications for tonotopy-related gating function and cross-modal modulation.
Eur J Neurosci 2007, 26: 3524–3535.

Okamoto K, Imbe H, Kimura A, Donishi T, Tamai Y, Senba E.
Activation of central 5HT2A receptors reduces the craniofacial nociception of rats.
Neuroscience 2007, 147: 1090–1102.

Kimura A, Donishi T, Okamoto K, Imbe H, Tamai Y.
Efferent connections of the ventral auditory area in the rat cortex: implications for auditory processing related to emotion.
Eur J Neurosci 2007, 25: 2819–2834.

2006

Okamoto K, Kimura A, Donishi T, Imbe H, Yuko Nishie, Haruhiko Matsushita, Tamai Y, Senba E.
Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus produced by acute injury to the masseter muscle during persistent temporomandibular joint inflammation in rats.
Neuroscience 2006, 143: 597–606.

Imbe H, Iwai-Liao Y, Senba E.
Stress-induced hyperalgesia: animal models and putative mechanisms.
Front Biosci 2006, 11: 2179-2192.

Okamoto K, Kimura A, Donishi T, Imbe H, Goda K, Kawanishi K, Tamai Y, Senba E.
Persistent monoarthritis of the temporomandibular joint region enhances nocifensive behavior and lumbar spinal Fos expression after noxious stimulation to the hindpaw in rats.
Exp Brain Res 2006, 170: 358–367.

Han W, Hata H, Imbe H, Liu QR, Takamatsu Y, Koizumi M, Murphy NP, Senba E, Uhl GR, Sora I, Ikeda K.
Increased body weight in mice lacking mu-opioid receptors.
Neuroreport 2006, 17: 941-944.

Oh SH, Imbe H, Iwai-Liao Y.
TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by subsequent formalin injection of the masseter or hindpaw of rats.
Okajimas Folia Anat Jpn 2006, 83: 43-52.

2005

Okamoto K, Kimura A, Donishi T, Imbe H, Senba E, Tamai Y.
Central serotonin 3 receptors play an important role in the modulation of nociceptive neural activity of trigeminal subnucleus caudalis and nocifensive orofacial behavior in rats with persistent temporomandibular joint inflammation.
Neuroscience 2005, 135: 569–581.

Okamoto K, Imbe H, Akimasa Tashiro, Kimura A, Donishi T, Tamai Y, Senba E.
The role of peripheral 5HT2A and 5HT1A receptors on the orofacial formalin test in rats with persistent temporomandibular joint inflammation.
Neuroscience 2005, 130: 465–474.

Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E.
Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly.
Neurosci Res 2005, 53: 129-139.

Kumabe S, Nakatsuka M, Iwai-Liao Y, Imbe H, Kim GS.
Morphological classification of mandibular dental arch forms by correlation and principal component analyses.
Okajimas Folia Anat Jpn 2005, 82: 67-77.

Imbe H, Okamoto K, Okamura T, Kumabe S, Nakatsuka M, Aikawa F, Iwai-Liao Y, Senba E.
Effects of peripheral inflammation on activation of ERK in the rostral ventromedial medulla.
Brain Res 2005, 1063: 151-158.

2004

Imbe H, Murakami S, Okamoto K, Iwai-Liao Y, Senba E.
The effects of acute and chronic restraint stress on activation of ERK in the rostral ventromedial medulla and locus coeruleus.
Pain 2004, 112: 361-371.

Okamoto K, Imbe H, Tashiro A, Kumabe S, Senba E.
Blockade of peripheral 5HT3 receptor attenuates the formalin-induced nocifensive behavior in persistent temporomandibular joint inflammation of rat.
Neurosci Lett 2004, 367: 259-263.

Imbe H, Abe T, Okamoto K, Sato M, Ito H, Kumabe S, Senba E.
Increase of galanin-like immunoreactivity in rat hypothalamic arcuate neurons after peripheral nerve injury.
Neurosci Lett 2004, 368: 102-106.

2003

Imbe H, Okamoto K, Kadoya T, Horie H, Senba E.
Galectin-1 is involved in the potentiation of neuropathic pain in the dorsal horn.
Brain Res 2003, 993: 72-83.

2002

Okamoto K, Imbe H, Morikawa Y, Itoh M, Sekimoto M, Nemoto K, Senba E.
5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats.
Pain 2002, 99: 133-143.

2001

Imbe H, Iwata K, Zhou QQ, Zou S, Dubner R, Ren K.
Orofacial deep and cutaneous tissue inflammation and trigeminal neuronal activation. Implications for persistent temporomandibular pain.
Cells Tissues Organs 2001, 169: 238-247.

Zhou QQ, Imbe H, Zou S, Dubner R, Ren K.
Selective upregulation of the flip-flop splice variants of AMPA receptor subunits in the rat spinal cord after hindpaw inflammation.
Brain Res Mol Brain Res 2001, 88: 186-193.

2000

Imbe H, Ren K.
The up-regulation of preprodynorphin mRNA in trigeminoparabrachial neurons after inflammation.
Neuroreport 2000, 11: 845-847.

1999

Imbe H, Ren K.
Orofacial deep and cutaneous tissue inflammation differentially upregulates preprodynorphin mRNA in the trigeminal and paratrigeminal nuclei of the rat.
Brain Res Mol Brain Res 1999, 67: 87-97.

Zhou QQ, Imbe H, Dubner R, Ren K.
Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats: implications for persistent orofacial pain.
J Comp Neurol 1999, 412: 276-291.

Imbe H, Dubner R, Ren K.
Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone: contribution of somatosensory-vagal-adrenal integration.
Brain Res 1999, 845: 165-175.

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