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ACTIVIN IS CRITICAL FOR THE DEVELOPMENT OF PAIN HYPERSENSITIVITY AFTER INFLAMMATION

Xu, Pin
http://rave.ohiolink.edu/etdc/view?acc_num=case1183753645

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Inflammatory pain is a major clinical challenge. The perception of pain is initiated by specialized sensory neurons in the Dorsal Root Ganglia (DRG) called nociceptors. Upon injury, neuropeptides including Calcitonin Gene-Related Peptide (CGRP) are released from nociceptors and the neuropeptide contributes to the development of abnormal pain. The studies in this thesis focus on the role of activin in regulating pain after skin inflammation. In this study, experimental peripheral inflammation was accompanied by increases in activin mRNA and activin immunoreactivity in both keratinocytes and infiltrating immune cells. The number of CGRP containing DRG neurons increased after inflammation, and this increase was among neurons that expressed the lectin IB4 or TrkA. These data indicate that some adult sensory neurons remain plastic and can increase CGRP expression after inflammation or activin administration. Strikingly, activin administration also induced thermal hyperalgesia and mechanical allodynia pain behaviors. I demonstrated that activin induced thermal hyperalgesia involved the sensitization of nociceptors through the Transient Receptor Potential Vallinoid subtype 1 (TRPV1). In addition to changing acute pain behaviors, activin also regulated neuropeptide gene transcription over chronic periods. Activin and nerve growth factor (NGF) worked synergistically to increase CGRP mRNA in adult DRG cultures. Biochemical and pharmacological studies indicate that this synergy was initiated by independent stimulation of receptors and intracellular signals, and our data suggest that activin and NGF effects converge on the CGRP promoter to regulate CGRP expression. Taken together, these data demonstrate that increased activin expression after inflammation results in both acute pain behaviors through sensitizing nociceptors and prolonged pain regulation by increasing CGRP expression.
Alison Hall (Advisor)
Biology, Neuroscience
ACTIVIN; CGRP; neurons; NGF; DRG; Sensory neurons; INFLAMMATION

Recommended Citations

Citations

  • Xu, P. (2007). ACTIVIN IS CRITICAL FOR THE DEVELOPMENT OF PAIN HYPERSENSITIVITY AFTER INFLAMMATION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1183753645

    APA Style (7th edition)

  • Xu, Pin. ACTIVIN IS CRITICAL FOR THE DEVELOPMENT OF PAIN HYPERSENSITIVITY AFTER INFLAMMATION. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1183753645.

    MLA Style (8th edition)

  • Xu, Pin. "ACTIVIN IS CRITICAL FOR THE DEVELOPMENT OF PAIN HYPERSENSITIVITY AFTER INFLAMMATION." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1183753645

    Chicago Manual of Style (17th edition)

case1183753645
961
© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.