Title page for etd-0127105-163018


[Back to Results | New Search]

URN etd-0127105-163018
Author Cheng-Haung Wang
Author's Email Address wang1211@adm.cgmh.org.tw
Statistics This thesis had been viewed 5617 times. Download 4347 times.
Department Biological Sciences
Year 2004
Semester 1
Degree Ph.D.
Type of Document
Language zh-TW.Big5 Chinese
Title The effects of Calpain-Cdk5-p35 pathway inhibition on rat spinal cord injury, acute pain, and morphine tolerance
Date of Defense 2005-01-20
Page Count 109
Keyword
  • cyclin-dependent kinase-5
  • spinal cord injury
  • calpain
  • morphine tolerance
  • Abstract Spinal cord injury, acute pain, and morphine tolerance are important issues in the clinical practice. A primary injury to the spinal cord causes both morphological and biochemical changes with initiation of the devastating secondary pathophysiological pathways that ultimately destroy CNS cells and cause degeneration of nerve fibers. Tissue injury is associated with sensitization of nociceptors and subsequent changes in the excitability of central neurons, known as central sensitization. Nociceptor sensitization and central sensitization are believed to underlie the development of primary and secondary hyperalgesia, respectively. The most efficacious drugs used to relieve pain are the opioid analgesics. Chronic administration leads to the development of tolerance. Tolerance is manifested as a decreased potency of the drug, so that progressively larger doses must be administered to achieve a given level of analgesia. The processes underlying opioid tolerance still need to be elucidated.
     Recently, it is found calpain-Cdk5 (cyclin-dependent kinase-5)-p35 pathway modulation implicated in neuroprotection, acute nociceptive response, and morphine analgesia. In this thesis, we evaluate calpain inhibitor-MDL28170 and Cdk5 inhibitor-roscovitine against rat spinal cord hemisection, formalin-induced acute nociceptive responses, and chronic morphine tolerance. We found calpain-Cdk5-p35 pathway inhibition could protect spinal cord hemisection and subsequent neurodegeneration, inhibit formalin-induced flinch response involving DARPP-32 (dopamine and c-AMP regulated phosphoprotein, MW=32 kDa) phosphorylation, and reverse right shifted morphine dose-response curve with upregulated ED50 (50% of effective dose) reduction. Taken together, calpain-Cdk5-p35 pathway inhibition is useful in the management of spinal cord injury, acute inflammatory pain, and attenuate morphine tolerance development with further clinical application.
    Advisory Committee
  • Jiin-Tsuey Cheng - chair
  • Chung-Lung Cho - co-chair
  • Ming-Hong Tai - co-chair
  • Yann-Jang Chen - co-chair
  • Jong-Kang Liu - advisor
  • Files
  • etd-0127105-163018.pdf
  • indicate access worldwide
    Date of Submission 2005-01-27

    [Back to Results | New Search]


    Browse | Search All Available ETDs

    If you have more questions or technical problems, please contact eThesys