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postgraduate thesis: The effects of astrocytic endothelin-1 in modulating inflammatory painprocessing

TitleThe effects of astrocytic endothelin-1 in modulating inflammatory painprocessing
Authors
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Chen, S. M. Y. [陳雯英]. (2012). The effects of astrocytic endothelin-1 in modulating inflammatory pain processing. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775258
Abstract Endothelin-1 (ET-1), a 21-amino acid peptide, exerts multiple functions including vasoconstriction, neurotransmission and neuromodulation. The correlation between ET-1 and pain was examined by localized injection into the animal showing that pain response was induced in the peripheral nervous system, but reduced in the central nervous system. In addition, the pathogenic effect of ET-1 in the nervous system was found to be cell-type specific as ET-1 expression was significantly induced in the astrocytes under certain pathological conditions such as stroke and Alzheimer’s disease. Therefore, in this study, it aims to determine the role of astrocytic ET-1 in inflammatory pain. To better illustrate such notion, transgenic mouse line over-expressing ET-1 in the astrocytes (GET-1) was generated. Under physiological conditions in GET-1 mice, it was revealed that its gross anatomy, in addition with thermal heat and mechanical pain-thresholds, were indistinguishable between GET-1 and its age-matched non-transgenic control (NTg). Inflammatory pain was then induced in the GET-1 mice and NTg mice by subcutaneous formalin injection. Spontaneous and heat-induced pain response were evaluated and analyzed based on the two phases of pain response (i.e. acute and tonic responses). Our results indicated that GET-1 mice exhibited less inflammatory pain-like response when compared to the NTg control, implicating that astrocytic ET-1 over-expression modulates inflammatory pain response. The molecular mechanism substantiating the reduction in this response may be due to the basal expression of pain-mediators in GET-1 mice. Further results showed that over-expression in astrocytic ET-1 evoke an up-regulation in calcitonin gene-related peptide (CGRP) as well as the glutamate transporter-1 (GLT-1), also known as excitatory amino-acid transporters (EAAT2). In addition, under formalin-induced pathological pain, over-expression in astrocytic ET-1 was found to negatively regulate GLT-1 transcription. These findings elucidate the extent that ET-1 contributes to the inflammatory pain pathway via ET-1 and GLT-1 interactions. Overall, this study not only pointed out the involvement of astrocytic ET-1 in inflammatory pain processing, but it also warrants further investigation into the molecular mechanism and potential therapeutic intervention of ET-1-mediated pain.
DegreeMaster of Philosophy
SubjectEndothelins.
Astrocytes.
Pain.
Dept/ProgramAnaesthesiology
Persistent Identifierhttp://hdl.handle.net/10722/181018

 

DC FieldValueLanguage
dc.contributor.authorChen, Samantha M. Y.-
dc.contributor.author陳雯英.-
dc.date.accessioned2013-02-17T02:42:15Z-
dc.date.available2013-02-17T02:42:15Z-
dc.date.issued2012-
dc.identifier.citationChen, S. M. Y. [陳雯英]. (2012). The effects of astrocytic endothelin-1 in modulating inflammatory pain processing. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775258-
dc.identifier.urihttp://hdl.handle.net/10722/181018-
dc.description.abstract Endothelin-1 (ET-1), a 21-amino acid peptide, exerts multiple functions including vasoconstriction, neurotransmission and neuromodulation. The correlation between ET-1 and pain was examined by localized injection into the animal showing that pain response was induced in the peripheral nervous system, but reduced in the central nervous system. In addition, the pathogenic effect of ET-1 in the nervous system was found to be cell-type specific as ET-1 expression was significantly induced in the astrocytes under certain pathological conditions such as stroke and Alzheimer’s disease. Therefore, in this study, it aims to determine the role of astrocytic ET-1 in inflammatory pain. To better illustrate such notion, transgenic mouse line over-expressing ET-1 in the astrocytes (GET-1) was generated. Under physiological conditions in GET-1 mice, it was revealed that its gross anatomy, in addition with thermal heat and mechanical pain-thresholds, were indistinguishable between GET-1 and its age-matched non-transgenic control (NTg). Inflammatory pain was then induced in the GET-1 mice and NTg mice by subcutaneous formalin injection. Spontaneous and heat-induced pain response were evaluated and analyzed based on the two phases of pain response (i.e. acute and tonic responses). Our results indicated that GET-1 mice exhibited less inflammatory pain-like response when compared to the NTg control, implicating that astrocytic ET-1 over-expression modulates inflammatory pain response. The molecular mechanism substantiating the reduction in this response may be due to the basal expression of pain-mediators in GET-1 mice. Further results showed that over-expression in astrocytic ET-1 evoke an up-regulation in calcitonin gene-related peptide (CGRP) as well as the glutamate transporter-1 (GLT-1), also known as excitatory amino-acid transporters (EAAT2). In addition, under formalin-induced pathological pain, over-expression in astrocytic ET-1 was found to negatively regulate GLT-1 transcription. These findings elucidate the extent that ET-1 contributes to the inflammatory pain pathway via ET-1 and GLT-1 interactions. Overall, this study not only pointed out the involvement of astrocytic ET-1 in inflammatory pain processing, but it also warrants further investigation into the molecular mechanism and potential therapeutic intervention of ET-1-mediated pain.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B47752580-
dc.subject.lcshEndothelins.-
dc.subject.lcshAstrocytes.-
dc.subject.lcshPain.-
dc.titleThe effects of astrocytic endothelin-1 in modulating inflammatory painprocessing-
dc.typePG_Thesis-
dc.identifier.hkulb4775258-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineAnaesthesiology-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4775258-
dc.date.hkucongregation2012-

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