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Author
Title Mechanistic Evaluation of Affective Dimensions of Pain in Rats
URL
Publication Date
Date Accessioned
Degree Level doctoral
University/Publisher University of Arizona
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.
Subjects/Keywords ongoing pain; pain; pain relief is rewarding; spontaneous pain; Medical Pharmacology; anterior cingulate cortex; measuring pain preclinically
Contributors Porreca, Frank (advisor); Porreca, Frank (committeemember); Dussor, Gregory (committeemember); French, Edward (committeemember); Ossipov, Michael (committeemember); Vanderah, Todd (committeemember)
Language en
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.
Country of Publication us
Record ID handle:10150/243095
Repository arizona-diss
Date Retrieved
Date Indexed 2020-04-23
Issued Date 2012-01-01 00:00:00

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…8 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…

…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. 9 CHAPTER 1 – NEUROBIOLOGY OF PAIN Pain is a multidimensional and fundamental life experience that is paramount…

…under normal circumstances, pain serves as a teaching signal that enables us to learn to avoid stimuli that have the potential to cause injury or damage to tissue. Pain is a warning to evade danger as well as a reminder to protect injured limbs or tissue…

…so that healing can take place. A key feature of pain is that it is unpleasant. Pain induces an aversive state that demands a behavioral response, i.e., a motivation to escape and to obtain relief. The experience of pain teaches us to avoid…

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