Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer
Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of...
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| Veröffentlicht in: | Molecular pain 2018-01, Vol.14, p.1744806918756406 |
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| creator | Watanabe, Moe Narita, Michiko Hamada, Yusuke Yamashita, Akira Tamura, Hideki Ikegami, Daigo Kondo, Takashige Shinzato, Tatsuto Shimizu, Takatsune Fukuchi, Yumi Muto, Akihiro Okano, Hideyuki Yamanaka, Akihiro Tawfik, Vivianne L Kuzumaki, Naoko Navratilova, Edita Porreca, Frank Narita, Minoru |
| description | Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals. Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states. |
| doi_str_mv | 10.1177/1744806918756406 |
| format | Article |
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The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals. Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1177/1744806918756406</identifier><identifier>PMID: 29357732</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Bone cancer ; Bone Neoplasms - complications ; Bone Neoplasms - physiopathology ; Cancer ; Cancer Pain - etiology ; Cancer Pain - pathology ; Cancer Pain - physiopathology ; Cell activation ; Cell Line, Tumor ; Chronic pain ; Dopamine receptors ; Dopaminergic Neurons - metabolism ; Dopaminergic Neurons - pathology ; Electrophysiology ; Excitability ; Hydroxylase ; Hyperalgesia ; Hyperalgesia - etiology ; Hyperalgesia - pathology ; Hyperalgesia - physiopathology ; Ligation ; Male ; Mesolimbic system ; Mice, Inbred C57BL ; Neuralgia ; Neuralgia - pathology ; Neurons ; Nucleus accumbens ; Nucleus Accumbens - pathology ; Nucleus Accumbens - physiopathology ; Osteosarcoma ; Osteosarcoma cells ; Pain ; Pain perception ; Sarcoma ; Sciatic nerve ; Sciatic Nerve - injuries ; Sciatic Nerve - pathology ; Sciatic Nerve - physiopathology ; Trauma ; Tyrosine 3-monooxygenase ; Ventral Tegmental Area - pathology ; Ventral Tegmental Area - physiopathology ; Ventral tegmentum</subject><ispartof>Molecular pain, 2018-01, Vol.14, p.1744806918756406</ispartof><rights>The Author(s) 2018</rights><rights>The Author(s) 2018. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2018 2018 SAGE Publications Inc., unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-def4eea357b4a91e64a43ec7c9bdc4d65f69b06f36e17184f789664a0da3e8d63</citedby><cites>FETCH-LOGICAL-c528t-def4eea357b4a91e64a43ec7c9bdc4d65f69b06f36e17184f789664a0da3e8d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802605/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802605/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,21945,27830,27901,27902,44921,45309,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29357732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watanabe, Moe</creatorcontrib><creatorcontrib>Narita, Michiko</creatorcontrib><creatorcontrib>Hamada, Yusuke</creatorcontrib><creatorcontrib>Yamashita, Akira</creatorcontrib><creatorcontrib>Tamura, Hideki</creatorcontrib><creatorcontrib>Ikegami, Daigo</creatorcontrib><creatorcontrib>Kondo, Takashige</creatorcontrib><creatorcontrib>Shinzato, Tatsuto</creatorcontrib><creatorcontrib>Shimizu, Takatsune</creatorcontrib><creatorcontrib>Fukuchi, Yumi</creatorcontrib><creatorcontrib>Muto, Akihiro</creatorcontrib><creatorcontrib>Okano, Hideyuki</creatorcontrib><creatorcontrib>Yamanaka, Akihiro</creatorcontrib><creatorcontrib>Tawfik, Vivianne L</creatorcontrib><creatorcontrib>Kuzumaki, Naoko</creatorcontrib><creatorcontrib>Navratilova, Edita</creatorcontrib><creatorcontrib>Porreca, Frank</creatorcontrib><creatorcontrib>Narita, Minoru</creatorcontrib><title>Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer</title><title>Molecular pain</title><addtitle>Mol Pain</addtitle><description>Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals. Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.</description><subject>Animals</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - complications</subject><subject>Bone Neoplasms - physiopathology</subject><subject>Cancer</subject><subject>Cancer Pain - etiology</subject><subject>Cancer Pain - pathology</subject><subject>Cancer Pain - physiopathology</subject><subject>Cell activation</subject><subject>Cell Line, Tumor</subject><subject>Chronic pain</subject><subject>Dopamine receptors</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Dopaminergic Neurons - pathology</subject><subject>Electrophysiology</subject><subject>Excitability</subject><subject>Hydroxylase</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - etiology</subject><subject>Hyperalgesia - pathology</subject><subject>Hyperalgesia - physiopathology</subject><subject>Ligation</subject><subject>Male</subject><subject>Mesolimbic system</subject><subject>Mice, Inbred C57BL</subject><subject>Neuralgia</subject><subject>Neuralgia - pathology</subject><subject>Neurons</subject><subject>Nucleus accumbens</subject><subject>Nucleus Accumbens - pathology</subject><subject>Nucleus Accumbens - physiopathology</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma cells</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Sarcoma</subject><subject>Sciatic nerve</subject><subject>Sciatic Nerve - injuries</subject><subject>Sciatic Nerve - pathology</subject><subject>Sciatic Nerve - physiopathology</subject><subject>Trauma</subject><subject>Tyrosine 3-monooxygenase</subject><subject>Ventral Tegmental Area - pathology</subject><subject>Ventral Tegmental Area - physiopathology</subject><subject>Ventral tegmentum</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1UU1r3DAQFaWl-WjvPQVBz04kS5bsSyCEtgkEemnPQpbHjhZb2oxsw97zw6tl0zQJ9KTHvI8Z8Qj5wtk551pfcC1lzVTDa10pydQ7crwfFfvZ-xf4iJyktGFMaKb4R3JUNqLSWpTH5PHKzX61s4-Bxp6uEGa0I51hmDLMyCJY2sWtnXwAHLyjARaMIVGEFTBBols738cxZm6vH8fY7YK3mU_LOPsw0B7jlG24AvVhs-CORqRtDECdDQ7wE_nQ2zHB56f3lPz-_u3X9U1x9_PH7fXVXeGqsp6LDnoJYPPprbQNByWtFOC0a9rOyU5VvWpapnqhgGtey17Xjcoi1lkBdafEKbk85G6XdoLOHT5rtugnizsTrTevmeDvzRBXU9WsVKzKAV-fAjA-LJBms4kLhnyzKaWUgjHNRVaxg8phTAmhf97Amdn3Zt72li1nLy97NvwtKguKgyDZAf5t_W_gH6PvpO0</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Watanabe, Moe</creator><creator>Narita, Michiko</creator><creator>Hamada, Yusuke</creator><creator>Yamashita, Akira</creator><creator>Tamura, Hideki</creator><creator>Ikegami, Daigo</creator><creator>Kondo, Takashige</creator><creator>Shinzato, Tatsuto</creator><creator>Shimizu, Takatsune</creator><creator>Fukuchi, Yumi</creator><creator>Muto, Akihiro</creator><creator>Okano, Hideyuki</creator><creator>Yamanaka, Akihiro</creator><creator>Tawfik, Vivianne L</creator><creator>Kuzumaki, Naoko</creator><creator>Navratilova, Edita</creator><creator>Porreca, Frank</creator><creator>Narita, Minoru</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20180101</creationdate><title>Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer</title><author>Watanabe, Moe ; Narita, Michiko ; Hamada, Yusuke ; Yamashita, Akira ; Tamura, Hideki ; Ikegami, Daigo ; Kondo, Takashige ; Shinzato, Tatsuto ; Shimizu, Takatsune ; Fukuchi, Yumi ; Muto, Akihiro ; Okano, Hideyuki ; Yamanaka, Akihiro ; Tawfik, Vivianne L ; Kuzumaki, Naoko ; Navratilova, Edita ; Porreca, Frank ; Narita, Minoru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-def4eea357b4a91e64a43ec7c9bdc4d65f69b06f36e17184f789664a0da3e8d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Bone cancer</topic><topic>Bone Neoplasms - complications</topic><topic>Bone Neoplasms - physiopathology</topic><topic>Cancer</topic><topic>Cancer Pain - etiology</topic><topic>Cancer Pain - pathology</topic><topic>Cancer Pain - physiopathology</topic><topic>Cell activation</topic><topic>Cell Line, Tumor</topic><topic>Chronic pain</topic><topic>Dopamine receptors</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Dopaminergic Neurons - pathology</topic><topic>Electrophysiology</topic><topic>Excitability</topic><topic>Hydroxylase</topic><topic>Hyperalgesia</topic><topic>Hyperalgesia - etiology</topic><topic>Hyperalgesia - pathology</topic><topic>Hyperalgesia - physiopathology</topic><topic>Ligation</topic><topic>Male</topic><topic>Mesolimbic system</topic><topic>Mice, Inbred C57BL</topic><topic>Neuralgia</topic><topic>Neuralgia - pathology</topic><topic>Neurons</topic><topic>Nucleus accumbens</topic><topic>Nucleus Accumbens - pathology</topic><topic>Nucleus Accumbens - physiopathology</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma cells</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Sarcoma</topic><topic>Sciatic nerve</topic><topic>Sciatic Nerve - injuries</topic><topic>Sciatic Nerve - pathology</topic><topic>Sciatic Nerve - physiopathology</topic><topic>Trauma</topic><topic>Tyrosine 3-monooxygenase</topic><topic>Ventral Tegmental Area - pathology</topic><topic>Ventral Tegmental Area - physiopathology</topic><topic>Ventral tegmentum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watanabe, Moe</creatorcontrib><creatorcontrib>Narita, Michiko</creatorcontrib><creatorcontrib>Hamada, Yusuke</creatorcontrib><creatorcontrib>Yamashita, Akira</creatorcontrib><creatorcontrib>Tamura, Hideki</creatorcontrib><creatorcontrib>Ikegami, Daigo</creatorcontrib><creatorcontrib>Kondo, Takashige</creatorcontrib><creatorcontrib>Shinzato, Tatsuto</creatorcontrib><creatorcontrib>Shimizu, Takatsune</creatorcontrib><creatorcontrib>Fukuchi, Yumi</creatorcontrib><creatorcontrib>Muto, Akihiro</creatorcontrib><creatorcontrib>Okano, Hideyuki</creatorcontrib><creatorcontrib>Yamanaka, Akihiro</creatorcontrib><creatorcontrib>Tawfik, Vivianne L</creatorcontrib><creatorcontrib>Kuzumaki, Naoko</creatorcontrib><creatorcontrib>Navratilova, Edita</creatorcontrib><creatorcontrib>Porreca, Frank</creatorcontrib><creatorcontrib>Narita, Minoru</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanabe, Moe</au><au>Narita, Michiko</au><au>Hamada, Yusuke</au><au>Yamashita, Akira</au><au>Tamura, Hideki</au><au>Ikegami, Daigo</au><au>Kondo, Takashige</au><au>Shinzato, Tatsuto</au><au>Shimizu, Takatsune</au><au>Fukuchi, Yumi</au><au>Muto, Akihiro</au><au>Okano, Hideyuki</au><au>Yamanaka, Akihiro</au><au>Tawfik, Vivianne L</au><au>Kuzumaki, Naoko</au><au>Navratilova, Edita</au><au>Porreca, Frank</au><au>Narita, Minoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer</atitle><jtitle>Molecular pain</jtitle><addtitle>Mol Pain</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>14</volume><spage>1744806918756406</spage><pages>1744806918756406-</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals. Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>29357732</pmid><doi>10.1177/1744806918756406</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bone cancer Bone Neoplasms - complications Bone Neoplasms - physiopathology Cancer Cancer Pain - etiology Cancer Pain - pathology Cancer Pain - physiopathology Cell activation Cell Line, Tumor Chronic pain Dopamine receptors Dopaminergic Neurons - metabolism Dopaminergic Neurons - pathology Electrophysiology Excitability Hydroxylase Hyperalgesia Hyperalgesia - etiology Hyperalgesia - pathology Hyperalgesia - physiopathology Ligation Male Mesolimbic system Mice, Inbred C57BL Neuralgia Neuralgia - pathology Neurons Nucleus accumbens Nucleus Accumbens - pathology Nucleus Accumbens - physiopathology Osteosarcoma Osteosarcoma cells Pain Pain perception Sarcoma Sciatic nerve Sciatic Nerve - injuries Sciatic Nerve - pathology Sciatic Nerve - physiopathology Trauma Tyrosine 3-monooxygenase Ventral Tegmental Area - pathology Ventral Tegmental Area - physiopathology Ventral tegmentum |
| title | Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer |
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