Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats
•Effects of Botulinum toxin A (BTX-A) on central monoamines and their metabolites were analyzed.•Antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations.•Monoamine hypothesis: low levels of serotonin (5-HT), noradrenaline (NA) and/or dopamine (DA) linked to...
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| Veröffentlicht in: | Neuroscience letters 2016-03, Vol.617, p.213-217 |
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| creator | Ibragić, S. Matak, I. Dračić, A. Smajlović, A. Muminović, M. Proft, F. Sofić, E. Lacković, Z. Riederer, P. |
| description | •Effects of Botulinum toxin A (BTX-A) on central monoamines and their metabolites were analyzed.•Antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations.•Monoamine hypothesis: low levels of serotonin (5-HT), noradrenaline (NA) and/or dopamine (DA) linked to depression.•Observed increased NA and 5-HT concentrations might play a role in BTX-A efficacy for treatment of depression.•Changes in neurotransmission by BTX may be able to influence depression, sleep and pain.
Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression. |
| doi_str_mv | 10.1016/j.neulet.2016.02.020 |
| format | Article |
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Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/j.neulet.2016.02.020</identifier><identifier>PMID: 26876447</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Amygdala - drug effects ; Amygdala - metabolism ; Animals ; Biogenic Monoamines - metabolism ; Botulinum neurotoxin type A ; Botulinum Toxins, Type A - pharmacology ; Brain - drug effects ; Brain - metabolism ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Depression ; Face ; High performance liquid chromatography with electrochemical detection ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Injections ; Male ; Monoamines ; Pain ; Rats, Wistar ; Trigeminal Nuclei - drug effects ; Trigeminal Nuclei - metabolism</subject><ispartof>Neuroscience letters, 2016-03, Vol.617, p.213-217</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-187a1e0e4627e98b87342cccafd45e9eb1fe1b96d22ed697c0466768f172fa983</citedby><cites>FETCH-LOGICAL-c441t-187a1e0e4627e98b87342cccafd45e9eb1fe1b96d22ed697c0466768f172fa983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304394016300878$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26876447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ibragić, S.</creatorcontrib><creatorcontrib>Matak, I.</creatorcontrib><creatorcontrib>Dračić, A.</creatorcontrib><creatorcontrib>Smajlović, A.</creatorcontrib><creatorcontrib>Muminović, M.</creatorcontrib><creatorcontrib>Proft, F.</creatorcontrib><creatorcontrib>Sofić, E.</creatorcontrib><creatorcontrib>Lacković, Z.</creatorcontrib><creatorcontrib>Riederer, P.</creatorcontrib><title>Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>•Effects of Botulinum toxin A (BTX-A) on central monoamines and their metabolites were analyzed.•Antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations.•Monoamine hypothesis: low levels of serotonin (5-HT), noradrenaline (NA) and/or dopamine (DA) linked to depression.•Observed increased NA and 5-HT concentrations might play a role in BTX-A efficacy for treatment of depression.•Changes in neurotransmission by BTX may be able to influence depression, sleep and pain.
Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression.</description><subject>Amygdala - drug effects</subject><subject>Amygdala - metabolism</subject><subject>Animals</subject><subject>Biogenic Monoamines - metabolism</subject><subject>Botulinum neurotoxin type A</subject><subject>Botulinum Toxins, Type A - pharmacology</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Depression</subject><subject>Face</subject><subject>High performance liquid chromatography with electrochemical detection</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Injections</subject><subject>Male</subject><subject>Monoamines</subject><subject>Pain</subject><subject>Rats, Wistar</subject><subject>Trigeminal Nuclei - drug effects</subject><subject>Trigeminal Nuclei - metabolism</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFqHCEUhqUkNNukb1CKl7nobNRxdbwphJC2gUBukmtxnGPrMupWndB9hLx1TTbNZeGAqN9_Duf_EfpEyZoSKi626wjLDHXN2m1NWCvyDq3oIFknlWRHaEV6wrtecXKCPpSyJYRs6Ia_RydMDFJwLlfo6do5sLXg5PCY6jL7uARc0x8fcd3vAF9iZ6w3M_Zx20CfIm4VUkwm-AgFmzjh-gt8xgGqGdPsa3tt8gKxpLz_gmcfRm9fwJBqynjMpv1n-Nm6vaDZ1HKGjp2ZC3x8PU_Rw7fr-6sf3e3d95ury9vOck5r1_YzFAhwwSSoYRxkz5m11riJb0DBSB3QUYmJMZiEkpZwIaQYHJXMGTX0p-j80HeX0-8FStXBFwvzbCKkpWgqFWmWsV41lB9Qm1MpGZzeZR9M3mtK9HMIeqsPIejnEDRhrUiTfX6dsIwBpjfRP9cb8PUAQNvz0UPWxXqIFiafm8d6Sv7_E_4C1jucoA</recordid><startdate>20160323</startdate><enddate>20160323</enddate><creator>Ibragić, S.</creator><creator>Matak, I.</creator><creator>Dračić, A.</creator><creator>Smajlović, A.</creator><creator>Muminović, M.</creator><creator>Proft, F.</creator><creator>Sofić, E.</creator><creator>Lacković, Z.</creator><creator>Riederer, P.</creator><general>Elsevier B.V</general><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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20160323</creationdate><title>Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats</title><author>Ibragić, S. ; Matak, I. ; Dračić, A. ; Smajlović, A. ; Muminović, M. ; Proft, F. ; Sofić, E. ; Lacković, Z. ; Riederer, P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-187a1e0e4627e98b87342cccafd45e9eb1fe1b96d22ed697c0466768f172fa983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amygdala - drug effects</topic><topic>Amygdala - metabolism</topic><topic>Animals</topic><topic>Biogenic Monoamines - metabolism</topic><topic>Botulinum neurotoxin type A</topic><topic>Botulinum Toxins, Type A - pharmacology</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Depression</topic><topic>Face</topic><topic>High performance liquid chromatography with electrochemical detection</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - metabolism</topic><topic>Injections</topic><topic>Male</topic><topic>Monoamines</topic><topic>Pain</topic><topic>Rats, Wistar</topic><topic>Trigeminal Nuclei - drug effects</topic><topic>Trigeminal Nuclei - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ibragić, S.</creatorcontrib><creatorcontrib>Matak, I.</creatorcontrib><creatorcontrib>Dračić, A.</creatorcontrib><creatorcontrib>Smajlović, A.</creatorcontrib><creatorcontrib>Muminović, M.</creatorcontrib><creatorcontrib>Proft, F.</creatorcontrib><creatorcontrib>Sofić, E.</creatorcontrib><creatorcontrib>Lacković, Z.</creatorcontrib><creatorcontrib>Riederer, P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ibragić, S.</au><au>Matak, I.</au><au>Dračić, A.</au><au>Smajlović, A.</au><au>Muminović, M.</au><au>Proft, F.</au><au>Sofić, E.</au><au>Lacković, Z.</au><au>Riederer, P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2016-03-23</date><risdate>2016</risdate><volume>617</volume><spage>213</spage><epage>217</epage><pages>213-217</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><abstract>•Effects of Botulinum toxin A (BTX-A) on central monoamines and their metabolites were analyzed.•Antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations.•Monoamine hypothesis: low levels of serotonin (5-HT), noradrenaline (NA) and/or dopamine (DA) linked to depression.•Observed increased NA and 5-HT concentrations might play a role in BTX-A efficacy for treatment of depression.•Changes in neurotransmission by BTX may be able to influence depression, sleep and pain.
Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>26876447</pmid><doi>10.1016/j.neulet.2016.02.020</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amygdala - drug effects Amygdala - metabolism Animals Biogenic Monoamines - metabolism Botulinum neurotoxin type A Botulinum Toxins, Type A - pharmacology Brain - drug effects Brain - metabolism Corpus Striatum - drug effects Corpus Striatum - metabolism Depression Face High performance liquid chromatography with electrochemical detection Hypothalamus - drug effects Hypothalamus - metabolism Injections Male Monoamines Pain Rats, Wistar Trigeminal Nuclei - drug effects Trigeminal Nuclei - metabolism |
| title | Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats |
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