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Neurokinin 1 receptors and their rol...

Largent-Milnes, Tally Marie.

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Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward./
Author:	Largent-Milnes, Tally Marie.
Description:	245 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2987.
Contained By:	Dissertation Abstracts International71-05B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3403269
ISBN:	9781109765403

Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward.
Largent-Milnes, Tally Marie.

Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward. - 245 p.

Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2987.

Thesis (Ph.D.)--The University of Arizona, 2010.

Pain is the most common and debilitating sign of a medical problem, with nearly 15 million patients suffering from chronic pain, including neuropathic pain. Widely used therapies for treating neuropathic pain include tri-cyclic antidepressants, opioids, anticonvulsants, non-steroidal anti-inflammatory agents and combinations thereof. Despite the abundance of treatments, the management of chronic pain remains difficult due to an inability for many patients to achieve appropriate pain relief at doses which are tolerable over long periods of time.

ISBN: 9781109765403Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward.
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020 $a 9781109765403
035 $a (UMI)AAI3403269
035 $a AAI3403269
040 $a UMI $c UMI
100 1 $a Largent-Milnes, Tally Marie. $3 1682534
245 1 0 $a Neurokinin 1 receptors and their role in opioid-induced hyperalgesia, antinociceptive tolerance and reward.
300 $a 245 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2987.
500 $a Adviser: Todd W. Vanderah.
502 $a Thesis (Ph.D.)--The University of Arizona, 2010.
520 $a Pain is the most common and debilitating sign of a medical problem, with nearly 15 million patients suffering from chronic pain, including neuropathic pain. Widely used therapies for treating neuropathic pain include tri-cyclic antidepressants, opioids, anticonvulsants, non-steroidal anti-inflammatory agents and combinations thereof. Despite the abundance of treatments, the management of chronic pain remains difficult due to an inability for many patients to achieve appropriate pain relief at doses which are tolerable over long periods of time.
520 $a Opiates (natural products), or opioids (synthetic derivatives), are considered the gold standard of analgesic care, though with little efficacy for neuropathic pain. Opioids are associated with unwanted side effects, including paradoxical pain and abuse liability that may result from several nervous system adaptations within the pain modulating neural network. These dose related side effects become more prevalent as clinicians try to overcome analgesic tolerance.
520 $a Molecular mechanisms underlying these unwanted side effects have been studied extensively, and the literature purports a variety of contributing factors and neurobiological adaptations. The studies herein describe additional molecular adaptations and novel pharmacological approaches to counteract these changes. First, the contributions of neurobiological remodeling within a single receptor system (the opioid system) were investigated in the spinal dorsal horn after peripheral nerve ligation and chronic exposure to an opioid agonist in combination with an ultra-low-dose of opioid antagonist. The effects of the ultra-low-dose opioid antagonist naltrexone on the efficacy of oxycodone for neuropathic pain were investigated after both central and systemic administration.
520 $a Secondly, molecular remodeling occurs across different receptor systems in the pain network, including altered regulation of pronociceptive molecules (e.g. substance P; SP). Previous studies have reported that opioid-induced hyperalgesia, tolerance and reward can be prevented by a blockade or ablation of SP activity at the neurokinin 1 receptor (NK1). We have characterized single compounds, rationally designed to act as opioid agonists and an NK1 antagonist using in vitro assays and the efficacy in vivo using rodent models of pain, antinociceptive tolerance and reward. Collectively, these studies validate the concept of targeting multiple neurobiological adaptations as a therapeutic option for neuropathic pain and reducing opioid-mediated side effects.
590 $a School code: 0009.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Biology, Neurobiology. $3 1681328
690 $a 0419
690 $a 0421
710 2 $a The University of Arizona. $b Medical Pharmacology. $3 1682535
773 0 $t Dissertation Abstracts International $g 71-05B.
790 1 0 $a Vanderah, Todd W., $e advisor
790 1 0 $a Porreca, Frank $e committee member
790 1 0 $a Hruby, Victor J. $e committee member
790 1 0 $a French, Edward D. $e committee member
790 1 0 $a King-Deeny, Tamara $e committee member
790 $a 0009
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3403269