Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine
Identifieur interne : 000005 ( Pmc/Corpus ); précédent : 000004; suivant : 000006Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine
Auteurs : James Brian Mcalvin ; Changyou Zhan ; Jenny C. Dohlman ; Paraskevi E. Kolovou ; Borja Salvador-Culla ; Daniel S. KohaneSource :
- Investigative Ophthalmology & Visual Science [ 0146-0404 ] ; 2015.
Abstract
Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α2-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied.
Solutions of TTX ± dexmedetomidine, TTX ± clonidine, STX ± dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration.
Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions.
Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.
Url:
DOI: 10.1167/iovs.15-16591
PubMed: 26066750
PubMed Central: 4468909
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine</title><author><name sortKey="Mcalvin, James Brian" sort="Mcalvin, James Brian" uniqKey="Mcalvin J" first="James Brian" last="Mcalvin">James Brian Mcalvin</name><affiliation><nlm:aff id="aff1">Department of Medicine Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Zhan, Changyou" sort="Zhan, Changyou" uniqKey="Zhan C" first="Changyou" last="Zhan">Changyou Zhan</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Dohlman, Jenny C" sort="Dohlman, Jenny C" uniqKey="Dohlman J" first="Jenny C." last="Dohlman">Jenny C. Dohlman</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Kolovou, Paraskevi E" sort="Kolovou, Paraskevi E" uniqKey="Kolovou P" first="Paraskevi E." last="Kolovou">Paraskevi E. Kolovou</name><affiliation><nlm:aff id="aff3">Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Salvador Culla, Borja" sort="Salvador Culla, Borja" uniqKey="Salvador Culla B" first="Borja" last="Salvador-Culla">Borja Salvador-Culla</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Kohane, Daniel S" sort="Kohane, Daniel S" uniqKey="Kohane D" first="Daniel S." last="Kohane">Daniel S. Kohane</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26066750</idno><idno type="pmc">4468909</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468909</idno><idno type="RBID">PMC:4468909</idno><idno type="doi">10.1167/iovs.15-16591</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000005</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000005</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine</title><author><name sortKey="Mcalvin, James Brian" sort="Mcalvin, James Brian" uniqKey="Mcalvin J" first="James Brian" last="Mcalvin">James Brian Mcalvin</name><affiliation><nlm:aff id="aff1">Department of Medicine Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Zhan, Changyou" sort="Zhan, Changyou" uniqKey="Zhan C" first="Changyou" last="Zhan">Changyou Zhan</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Dohlman, Jenny C" sort="Dohlman, Jenny C" uniqKey="Dohlman J" first="Jenny C." last="Dohlman">Jenny C. Dohlman</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Kolovou, Paraskevi E" sort="Kolovou, Paraskevi E" uniqKey="Kolovou P" first="Paraskevi E." last="Kolovou">Paraskevi E. Kolovou</name><affiliation><nlm:aff id="aff3">Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Salvador Culla, Borja" sort="Salvador Culla, Borja" uniqKey="Salvador Culla B" first="Borja" last="Salvador-Culla">Borja Salvador-Culla</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States</nlm:aff></affiliation></author><author><name sortKey="Kohane, Daniel S" sort="Kohane, Daniel S" uniqKey="Kohane D" first="Daniel S." last="Kohane">Daniel S. Kohane</name><affiliation><nlm:aff id="aff2">Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</nlm:aff></affiliation></author></analytic><series><title level="j">Investigative Ophthalmology & Visual Science</title><idno type="ISSN">0146-0404</idno><idno type="eISSN">1552-5783</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="st1"><title>Purpose.</title><p>Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α<sub>2</sub>-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied.</p></sec><sec id="st2"><title>Methods.</title><p>Solutions of TTX ± dexmedetomidine, TTX ± clonidine, STX ± dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration.</p></sec><sec id="st3"><title>Results.</title><p>Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions.</p></sec><sec id="st4"><title>Conclusions.</title><p>Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Invest Ophthalmol Vis Sci</journal-id><journal-id journal-id-type="iso-abbrev">Invest. Ophthalmol. Vis. Sci</journal-id><journal-id journal-id-type="hwp">iovs</journal-id><journal-id journal-id-type="pmc">iovs</journal-id><journal-id journal-id-type="publisher-id">iovs</journal-id><journal-title-group><journal-title>Investigative Ophthalmology & Visual Science</journal-title></journal-title-group><issn pub-type="ppub">0146-0404</issn><issn pub-type="epub">1552-5783</issn><publisher><publisher-name>The Association for Research in Vision and Ophthalmology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26066750</article-id><article-id pub-id-type="pmc">4468909</article-id><article-id pub-id-type="doi">10.1167/iovs.15-16591</article-id><article-id pub-id-type="sici">iovs-56-05-57</article-id><article-id pub-id-type="publisher-id">IOVS-15-16591</article-id><article-categories><subj-group subj-group-type="heading"><subject>Physiology and Pharmacology</subject></subj-group></article-categories><title-group><article-title>Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine</article-title><alt-title alt-title-type="runhead">DMED Prolongs Corneal Anesthesia From S1CSBs</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>McAlvin</surname><given-names>James Brian</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhan</surname><given-names>Changyou</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dohlman</surname><given-names>Jenny C.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kolovou</surname><given-names>Paraskevi E.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Salvador-Culla</surname><given-names>Borja</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kohane</surname><given-names>Daniel S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><aff id="aff1"><label>1</label>Department of Medicine Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</aff><aff id="aff2"><label>2</label>Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, United States</aff><aff id="aff3"><label>3</label>Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States</aff></contrib-group><author-notes><corresp id="cor1">Correspondence: Daniel S. Kohane, Laboratory for Biomaterials and Drug Delivery, Department of Anesthesia, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, 61 Binney Street, Room 361, Boston, MA 02115, USA; <email>daniel.kohane@childrens.harvard.edu</email>.</corresp></author-notes><pub-date pub-type="epub"><day>11</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2015</year></pub-date><volume>56</volume><issue>6</issue><fpage>3820</fpage><lpage>3826</lpage><history><date date-type="received"><day>1</day><month>2</month><year>2015</year></date><date date-type="accepted"><day>20</day><month>4</month><year>2015</year></date></history><permissions><copyright-statement>Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:title="pdf" xlink:href="i1552-5783-56-6-3820.pdf"></self-uri><abstract><sec id="st1"><title>Purpose.</title><p>Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α<sub>2</sub>-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied.</p></sec><sec id="st2"><title>Methods.</title><p>Solutions of TTX ± dexmedetomidine, TTX ± clonidine, STX ± dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration.</p></sec><sec id="st3"><title>Results.</title><p>Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions.</p></sec><sec id="st4"><title>Conclusions.</title><p>Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.</p></sec></abstract><abstract abstract-type="precis"><p>Prolonged duration corneal anesthesia from coadministration of site 1 sodium channel blockers and dexmedetomidine.</p></abstract><kwd-group><title>Keywords</title><kwd>tetrodotoxin</kwd><kwd>saxitoxin</kwd><kwd>dexmedetomidine</kwd><kwd>clonidine</kwd><kwd>corneal anesthesia</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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