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You searched for subject:(ongoing pain). Showing records 1 – 2 of 2 total matches.

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1. Okun, Alec. Mechanistic Evaluation of Affective Dimensions of Pain in Rats .

Degree: 2012, University of Arizona

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. Advisors/Committee Members: Porreca, Frank (advisor), Porreca, Frank (committeemember), Dussor, Gregory (committeemember), French, Edward (committeemember), Ossipov, Michael (committeemember), Vanderah, Todd (committeemember).

Subjects/Keywords: ongoing pain; pain; pain relief is rewarding; spontaneous pain; Medical Pharmacology; anterior cingulate cortex; measuring pain preclinically

…animals with ongoing pain will seek a context that has been paired with effective pain relief… …x29;. Furthermore, ongoing or spontaneous (stimulus-independent pain) is among… …ongoing pain or against both aspects of pain are needed (1, 20). In doing so… …reflective of ongoing pain (21). For this reason, the use of evoked responses as a… …reflecting the presence of ongoing or spontaneous pain, would add to our abilities to investigate… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Okun, A. (2012). Mechanistic Evaluation of Affective Dimensions of Pain in Rats . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/243095

Chicago Manual of Style (16th Edition):

Okun, Alec. “Mechanistic Evaluation of Affective Dimensions of Pain in Rats .” 2012. Doctoral Dissertation, University of Arizona. Accessed October 27, 2020. http://hdl.handle.net/10150/243095.

MLA Handbook (7th Edition):

Okun, Alec. “Mechanistic Evaluation of Affective Dimensions of Pain in Rats .” 2012. Web. 27 Oct 2020.

Vancouver:

Okun A. Mechanistic Evaluation of Affective Dimensions of Pain in Rats . [Internet] [Doctoral dissertation]. University of Arizona; 2012. [cited 2020 Oct 27]. Available from: http://hdl.handle.net/10150/243095.

Council of Science Editors:

Okun A. Mechanistic Evaluation of Affective Dimensions of Pain in Rats . [Doctoral Dissertation]. University of Arizona; 2012. Available from: http://hdl.handle.net/10150/243095

2. Remeniuk, Bethany Lynne. Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically .

Degree: 2015, University of Arizona

Pain is the most feared symptom of cancer and can impact patients' lives more than the cancer itself. Despite improvements in cancer prevention and detection, pain is often the first sign of cancer, with an estimated 70-75% of advanced stage cancer patients presenting with skeletal metastases. Cancer metastasis to the bone is associated with persistent pain that increases in intensity over time. Current treatments follow the World Health Organization (WHO) analgesic ladder for cancer pain management suggesting non-steroidal anti-inflammatory drugs (NSAIDs) for mild to moderate pain and opioids for moderate to severe pain. However, estimates indicate as many as 50-80% of cancer patients worldwide receive inadequate pain management. Moreover, opioid doses required for these patients are associated with adverse side effects further diminishing quality of life. Development of improved non-opioid therapies is dependent on increased understanding of mechanisms driving cancer pain and its relief. The objective of this dissertation was to characterize a rat model of cancer-induced bone pain, to develop approaches to measure both ongoing and breakthrough pain and to investigate the contribution of underlying inflammatory mechanisms to pain, bone destruction and bone remodeling. Using female Fischer F344/NhSD rats, histocompatible MAT B III mammary adenocarcinoma cells were sealed into the intramedullary space of the right rear tibia for a time course of 13 days. Ongoing pain was characterized based on the WHO 3-step ladder for pain management utilizing novel behavioral and neurochemical assays. Morphine and peripheral nerve block were sufficient to control ongoing pain, whereas NSAID treatment failed to provide pain relief. Cancer-bearing rats selectively displayed movement-induced breakthrough pain to a background of morphine-controlled ongoing pain. Furthermore, we determined that breakthrough pain is initiated, but not maintained, by peripheral afferent input from the tumor-bearing tibia using lidocaine administration prior to or following movement. For the final part of this study, we investigated the role of transient receptor potential vanilloid 1 (TRPV1) and interleukin-6 (IL-6) blockade, as these have been shown to be important mediators in animal models CIBP. Acute blockade of TRPV1 channels by AMG9810 selectively reversed inflammatory-induced pain, but failed to control evoked or ongoing CIBP. Acute blockade of interleukin-6 signaling by TB-2-081, an IL-6 receptor antagonist, successfully reversed evoke pain responses, but like AMG9810, failed to control ongoing pain. Sustained administration of TB-2-081 reversed cancer-induced tactile hypersensitivity and tumor-induced bone remodeling of the tibia. Further in vitro analysis revealed TB-2-081 functions by inhibiting the Jak/STAT cascade on both tumor cells and osteoblasts, suggesting that blockade of IL-6 signaling can effectively modulate the bone microenvironment to reduce tumor burden and pain. Combined, our data introduce a rat model of breast cancer bone… Advisors/Committee Members: Porreca, Frank (advisor), Ossipov, Michael (committeemember), Heimark, Ron (committeemember), Cress, Anne (committeemember), Porreca, Frank (committeemember).

Subjects/Keywords: breast cancer bone metastasis; cancer bone pain; interleukin-6; ongoing pain; transient receptor potential vanilloid-1; Cancer Biology; breakthrough pain

Ongoing Cancer-induced Bone Pain _________________________ 86 2.8.2 Breakthrough Cancer… …NEUROCHEMICAL ANALYSIS OF A RAT MODEL OF ONGOING CANCER-INDUCED BONE PAIN _____________ 89 3.1… …tactile hypersensitivity, but not ongoing pain… …DISCUSSION_______________________________________ 132 7.1 Ongoing Pain Study ________________________________________ 134 7.2… …cancer-induced bone pain, to develop approaches to measure both ongoing and breakthrough pain… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Remeniuk, B. L. (2015). Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/556862

Chicago Manual of Style (16th Edition):

Remeniuk, Bethany Lynne. “Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically .” 2015. Doctoral Dissertation, University of Arizona. Accessed October 27, 2020. http://hdl.handle.net/10150/556862.

MLA Handbook (7th Edition):

Remeniuk, Bethany Lynne. “Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically .” 2015. Web. 27 Oct 2020.

Vancouver:

Remeniuk BL. Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically . [Internet] [Doctoral dissertation]. University of Arizona; 2015. [cited 2020 Oct 27]. Available from: http://hdl.handle.net/10150/556862.

Council of Science Editors:

Remeniuk BL. Capturing Affective Dimensions of Cancer-Induced Bone Pain Preclinically . [Doctoral Dissertation]. University of Arizona; 2015. Available from: http://hdl.handle.net/10150/556862

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