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Virginia Commonwealth University

Pain

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Effects Of Chemotherapy On Motivated Behavior And Opioid Reward In Rats, Luke P. Legakis Jan 2018

Effects Of Chemotherapy On Motivated Behavior And Opioid Reward In Rats, Luke P. Legakis

Theses and Dissertations

Paclitaxel, vincristine, oxaliplatin, and bortezomib are cancer chemotherapy drugs with adverse effects that include chemotherapy-induced neuropathic pain (CINP) as well as depression of behavior and mood. In the clinical setting, opioids are often used concurrently with or following chemotherapy to treat pain related to the cancer or CINP, but repeated opioid exposure can also increase the risk of opioid abuse. This dissertation evaluated the effect of chemotherapy treatment on motivated behaviors and opioid reward in rats. The main findings of this evaluation are as follows: (1) Chemotherapy, at doses that produce robust and sustained mechanical hypersensitivity produce only weak or …


Effects Of Mu Opioid Receptor Agonists On Intracranial Self-Stimulation In The Absence And Presence Of “Pain” In Rats, Ahmad Altarifi May 2013

Effects Of Mu Opioid Receptor Agonists On Intracranial Self-Stimulation In The Absence And Presence Of “Pain” In Rats, Ahmad Altarifi

Theses and Dissertations

Pain is a significant health problem. Mu opioid receptor agonists are used clinically as analgesics, but their use is constrained by high abuse liability. Intracranial self-stimulation (ICSS) is a preclinical behavioral procedure that has been used to assess abuse potential of opioids, and drug-induced facilitation of ICSS is interpreted as an abuse-related effect. ICSS can also be used as a behavioral baseline to detect affective dimensions of pain. Specifically, pain-related depression of ICSS can model pain-related depression of behavior and mood, and drug-induced blockade of pain-related ICSS depression can serve as a measure of affective analgesia. This dissertation used mu …


Effect Of Cannabinoids On Pain-Stimulated And Pain-Depressed Behavior In Rats, Andrew Kwilasz May 2013

Effect Of Cannabinoids On Pain-Stimulated And Pain-Depressed Behavior In Rats, Andrew Kwilasz

Theses and Dissertations

Cannabinoids produce antinociception in many preclinical models of acute and chronic pain. In contrast, cannabinoids produce inconsistent analgesia in humans, showing little or no efficacy in treating acute pain, with modest efficacy in treating chronic inflammatory pain. This discrepancy may reflect an overreliance on preclinical assays of pain-stimulated behaviors, defined as behaviors that increase in rate or intensity following delivery of a noxious stimulus. In these assays, antinociception is indicated by a reduction in pain-stimulated behaviors, and antinociception is produced either by a reduction in sensory sensitivity to the noxious stimulus (i.e. true analgesia) or by false positive motor impairment. …


Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh Jan 2012

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …


Targeting The Endocannabinoid System To Reduce Nociception, Lamont Booker Apr 2011

Targeting The Endocannabinoid System To Reduce Nociception, Lamont Booker

Theses and Dissertations

Pain of various etiologies (e.g., visceral, inflammatory) can be a debilitating disorder that presents a problem of clinical relevance. While it is known that ∆9-tetrahydrocannabinol (THC) the primary psychoactive constituent found in marijuana produces analgesia in various rodent models of pain, its pharmacological properties are overshadowed by its psychomimetic effects. THC is the primary phytocannabinoid found in marijuana though other prevalent constituents such as the phytocannabinoids (e.g., cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV)) may possess antinociceptive actions without the psychomimetic effects associated with THC. Indeed, these phytocannabinoids act upon the endocannabinoid system (ECS) that is comprised of the …


Haploinsufficiency Of Rai1 And Its Effect On Bdnf Expression, Sun Kim Dec 2010

Haploinsufficiency Of Rai1 And Its Effect On Bdnf Expression, Sun Kim

Theses and Dissertations

Smith-Magenis Syndrome (SMS) [OMIM, #182290] is a congenital anomaly and mental retardation (MCA/MR) syndrome associated with deletion of chromosome17p11.2 [1]. The clinical phenotype has been well described and includes minor craniofacial anomalies, self-injurious behaviors as well as sleep disturbances, speech delays, and obesity [1,2,3]. The incidence of SMS is estimated to be ~ 1:15,000 - 25,000 births [2,6]. Among SMS patients, ~90% are comprised of 17p11.2 deletions, while ~10% have RAI1 mutations [8]. All 17p11.2 deletions associated with SMS include RAI1 deletion [10]. RAI1 is thought to function as a transcriptional factor although its cellular role is still unclear. First, …


The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot Jun 2009

The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot

Theses and Dissertations

Chronic neuropathic pain is often difficult to treat due to its resistance to therapeutic intervention. This is due in part to the poor understanding of the physiological mechanisms involved in the establishment and maintenance of neuropathic pain states. The neuropathic pain model, chronic constriction injury of the sciatic nerve, produced robust pain hypersensitivity in our mice. It also induced significant changes in the mitogen activated protein kinase family, and the cannabinoid and µ-opioid systems in three different brain areas involved in the modulation or regulation of pain states. CCI induced a 2.5 fold increase in mRNA of the kinase Raf-1 …