Persistent Link:
http://hdl.handle.net/10150/243095
Title:
Mechanistic Evaluation of Affective Dimensions of Pain in Rats
Author:
Okun, Alec
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release after 08-Feb-2013
Abstract:
Pain is the primary reason why patients seek medical care and there is a great unmet need for the development of pain relieving medications. The treatments that are currently available either have limited efficacy or are accompanied by a multitude of unwanted side effects. However, discovering novel therapeutics for the treatment of pain has been challenging. Part of the reason for this may be that that the ways in which pain is assessed in the preclinical setting are different from the way that it is evaluated clinically in human trials. The most common method for evaluating pain in preclinical models is to measure responses to evoked stimuli. However, a change in the threshold of response to evoked pain likely does not measure whether the unpleasant component of pain has actually been reduced. The most clinically relevant question for pain is whether the treatment actually makes the patients "feel better". Here, we demonstrate that the aversiveness of pain can be captured using motivated behavior to seek pain relief. We used conditioned place preference (CPP) to establish that animals with ongoing pain will seek a context that has been paired with effective pain relief, likely as a result of negative reinforcement. These studies allowed for mechanistic investigation. Our results show that: 1) effective pain relief can be achieved by either blocking noxious peripheral input or by directly attenuating pain related unpleasantness in the brain, and 2) pain relief is rewarding and activates the reward circuitry. These studies provide a basis for development of a future platform for drug discovery for pain.
Type:
text; Electronic Dissertation
Keywords:
ongoing pain; pain; pain relief is rewarding; spontaneous pain; Medical Pharmacology; anterior cingulate cortex; measuring pain preclinically
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Medical Pharmacology
Degree Grantor:
University of Arizona
Advisor:
Porreca, Frank

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleMechanistic Evaluation of Affective Dimensions of Pain in Ratsen_US
dc.creatorOkun, Alecen_US
dc.contributor.authorOkun, Alecen_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.releaseRelease after 08-Feb-2013en_US
dc.description.abstractPain is the primary reason why patients seek medical care and there is a great unmet need for the development of pain relieving medications. The treatments that are currently available either have limited efficacy or are accompanied by a multitude of unwanted side effects. However, discovering novel therapeutics for the treatment of pain has been challenging. Part of the reason for this may be that that the ways in which pain is assessed in the preclinical setting are different from the way that it is evaluated clinically in human trials. The most common method for evaluating pain in preclinical models is to measure responses to evoked stimuli. However, a change in the threshold of response to evoked pain likely does not measure whether the unpleasant component of pain has actually been reduced. The most clinically relevant question for pain is whether the treatment actually makes the patients "feel better". Here, we demonstrate that the aversiveness of pain can be captured using motivated behavior to seek pain relief. We used conditioned place preference (CPP) to establish that animals with ongoing pain will seek a context that has been paired with effective pain relief, likely as a result of negative reinforcement. These studies allowed for mechanistic investigation. Our results show that: 1) effective pain relief can be achieved by either blocking noxious peripheral input or by directly attenuating pain related unpleasantness in the brain, and 2) pain relief is rewarding and activates the reward circuitry. These studies provide a basis for development of a future platform for drug discovery for pain.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectongoing painen_US
dc.subjectpainen_US
dc.subjectpain relief is rewardingen_US
dc.subjectspontaneous painen_US
dc.subjectMedical Pharmacologyen_US
dc.subjectanterior cingulate cortexen_US
dc.subjectmeasuring pain preclinicallyen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Pharmacologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPorreca, Franken_US
dc.contributor.committeememberPorreca, Franken_US
dc.contributor.committeememberDussor, Gregoryen_US
dc.contributor.committeememberFrench, Edwarden_US
dc.contributor.committeememberOssipov, Michaelen_US
dc.contributor.committeememberVanderah, Todden_US
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