Bioinformatic Analysis of Angiotensin II Receptor Type 2 Expression and Its Potential Role in Neuropathic Pain
AdvisorVanderah, Todd W.
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PublisherThe University of Arizona.
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AbstractNeuropathic pain is a tremendous medical problem that afflicts millions. It is also distinct from other pain conditions. It persists in the absence of non-noxious stimuli or in response to formerly innocuous stimuli due to unique neurochemical and neurophysiological changes. These changes include acute excitation of peripheral neurons associated with regeneration of axons near the injury site. The causes of injuries leading to neuropathic pain include viral infection as well as trauma. Recently, a highly specific angiotensin II type 2 receptor (AGTR2) antagonist known as EMA401 showed efficacy as a treatment for postherpetic neuralgia in clinical trials. Together with previous immunohistochemical studies of the effects of EMA401 on in vitro neurite outgrowth and the presence of AGTR2 in rodent and human dorsal root ganglion, it ignited interest in AGTR2 as a pharmacological target for neuropathic pain. However, the role of AGTR2 in the modulation of neuropathic pain is not well understood. Despite previous studies, its anatomical expression in dorsal root ganglion and trigeminal ganglion remains uncertain. Additionally, few mechanisms for its modulation of nociceptive transmission have been extensively elucidated. Finally, differential expression of AGTR2 between mouse and human dorsal root ganglion has not been fully explored, especially given the availability of high-throughput expression data. Therefore, this study attempts to develop understanding of the role of AGTR2 in neuropathic pain through bioinformatic analysis of Gene Expression Omnibus (GEO) microarray data for multiple tissues and RNA Seq data acquired for human DRG.
Degree ProgramGraduate College