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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2011)

The use of animal models in the understanding of the neurobiology of pain perception is essential for the development of new pharmacotherapies. Yet, in modeling human clinical experience, there is a lack of meaningful and appropriate dependent variables of pain-related behaviors in the mouse. In this thesis, we address the problem of finding behavioral measures of pain in mice that fully encompass the range of experience inherent to human pain conditions. Therefore, in this work complex behaviors were assessed as potential measures of persistent pain in mice

We investigated a wide range of quality of life behaviors in three classic pain models: spared nerve injury, chronic constriction injury and injection of complete Freund's adjuvant. Mechanical hypersensitivity is prominent in each of these conditions and persists for many weeks. To assess more complex behavioral outcomes, home cage behavior was continuously monitored after injury and a battery of motor disability and affective behavior tests were performed on these mice. No model of chronic pain produced long-lasting changes to behaviors of daily life, either in the home cage or in tests of affect and disability.

Next, we observed behaviors in three other models of persistent pain: osteoarthritis, disc-degeneration, and dental pulp exposure. In a pilot study of the former two models, mice with joint degeneration were tested for locomotor ability and motivation, but showed no signs of disability. Lastly, we measured behavior in the setting of dental pulp inflammation, for which there is no standard method of measuring pain levels. As with other models, pulpal injury also did not impact behavior in the home cage. Instead, we used an operant assay of sucrose consumption as a measure of dental pain in mice. Data from this task suggest that pain can, in fact, influence some elements of complex behavior. However, as alteration in daily life activities is the feature that is so disrupted in patients with chronic pain, our results suggest that many murine pain models do not fully reflect the human conditions and raise questions regarding the limitations of these models in pain research.

    Cover page: Behavioral measures of persistent pain in mice
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2013)
    Dental pain, including toothache, is one of the most prevalent types of orofacial pain, causing severe, persistent pain that has a significant negative effect on quality of life, including eating disturbances, mood changes, and sleep disruption. As the primary cause of toothache pain is injury to the uniquely innervated dental pulp, rodent models of this injury provide the opportunity to study neurobiological mechanisms of tissue injury-induced persistent pain. Here we evaluated behavioral changes in mice with a dental pulp injury (DPI) produced by mechanically exposing the pulp to the oral environment. We monitored the daily life behaviors of mice with DPI, including measures of eating, drinking, and movement. During the first 48 hours, the only parameter affected by DPI was locomotion, which was reduced. There was also a significant short-term decrease in the amount of weight gained by DPI animals that was not related to food consumption. As cold allodynia is frequently observed in individuals experiencing toothache pain, we tested whether mice with DPI demonstrate an aversion to drinking cold liquids using a cold-sucrose consumption test. Surprisingly, mice with DPI increased their consumption of sucrose solution, to over 150% of baseline, regardless of temperature. Both the weight loss and increased sucrose intake in the first 2 days of injury were reversed by administration of indomethacin. These findings indicate that enhanced sucrose consumption may be a reliable measure of orofacial pain in rodents, and suggest that alterations in energy expenditure and motivational behaviors are under-recognized outcomes of tooth injury.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2013)
      Dental pain, including toothache, is one of the most prevalent types of orofacial pain, causing severe, persistent pain that has a significant negative effect on quality of life, including eating disturbances, mood changes, and sleep disruption. As the primary cause of toothache pain is injury to the uniquely innervated dental pulp, rodent models of this injury provide the opportunity to study neurobiological mechanisms of tissue injury-induced persistent pain. Here we evaluated behavioral changes in mice with a dental pulp injury (DPI) produced by mechanically exposing the pulp to the oral environment. We monitored the daily life behaviors of mice with DPI, including measures of eating, drinking, and movement. During the first 48 hours, the only parameter affected by DPI was locomotion, which was reduced. There was also a significant short-term decrease in the amount of weight gained by DPI animals that was not related to food consumption. As cold allodynia is frequently observed in individuals experiencing toothache pain, we tested whether mice with DPI demonstrate an aversion to drinking cold liquids using a cold-sucrose consumption test. Surprisingly, mice with DPI increased their consumption of sucrose solution, to over 150% of baseline, regardless of temperature. Both the weight loss and increased sucrose intake in the first 2 days of injury were reversed by administration of indomethacin. These findings indicate that enhanced sucrose consumption may be a reliable measure of orofacial pain in rodents, and suggest that alterations in energy expenditure and motivational behaviors are under-recognized outcomes of tooth injury.
        Cover page: Paradoxical surrogate markers of dental injury‐induced pain in the mouse
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2013)
        To what extent dorsal horn interneurons contribute to the modality specific processing of pain and itch messages is not known. Here, we report that loxp/cre-mediated CNS deletion of TR4, a testicular orphan nuclear receptor, results in loss of many excitatory interneurons in the superficial dorsal horn but preservation of primary afferents and spinal projection neurons. The interneuron loss is associated with a near complete absence of supraspinally integrated pain and itch behaviors, elevated mechanical withdrawal thresholds and loss of nerve injury-induced mechanical hypersensitivity, but reflex responsiveness to noxious heat, nerve injury-induced heat hypersensitivity, and tissue injury-induced heat and mechanical hypersensitivity are intact. We conclude that different subsets of dorsal horn excitatory interneurons contribute to tissue and nerve injury-induced heat and mechanical pain and that the full expression of supraspinally mediated pain and itch behaviors cannot be generated solely by nociceptor and pruritoceptor activation of projection neurons; concurrent activation of excitatory interneurons is essential.
          Cover page: Excitatory superficial dorsal horn interneurons are functionally heterogeneous and required for the full behavioral expression of pain and itch.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2013)
          To what extent dorsal horn interneurons contribute to the modality specific processing of pain and itch messages is not known. Here, we report that loxp/cre-mediated CNS deletion of TR4, a testicular orphan nuclear receptor, results in loss of many excitatory interneurons in the superficial dorsal horn but preservation of primary afferents and spinal projection neurons. The interneuron loss is associated with a near complete absence of supraspinally integrated pain and itch behaviors, elevated mechanical withdrawal thresholds and loss of nerve injury-induced mechanical hypersensitivity, but reflex responsiveness to noxious heat, nerve injury-induced heat hypersensitivity, and tissue injury-induced heat and mechanical hypersensitivity are intact. We conclude that different subsets of dorsal horn excitatory interneurons contribute to tissue and nerve injury-induced heat and mechanical pain and that the full expression of supraspinally mediated pain and itch behaviors cannot be generated solely by nociceptor and pruritoceptor activation of projection neurons; concurrent activation of excitatory interneurons is essential.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2019)
            The conversion of biomass to biofuels presents a solution to one of the largest global challenges of our era, climate change. A critical part of this pipeline is the process of breaking down cellulosic sugars from plant matter to be used by microbes containing biosynthetic pathways that produce biofuels or bioproducts. In this inquiry-based course, students complete a research project that isolates cellulase-producing bacteria from samples collected from the environment. After obtaining isolates, the students characterize the production of cellulases. Students then amplify and sequence the 16S rRNA genes of confirmed cellulase producers and use bioinformatic methods to identify the bacterial isolates. Throughout the course, students learn about the process of generating biofuels and bioproducts through the deconstruction of cellulosic biomass to form monosaccharides from the biopolymers in plant matter. The program relies heavily on active learning and enables students to connect microbiology with issues of sustainability. In addition, it provides exposure to basic microbiology, molecular biology, and biotechnology laboratory techniques and concepts. The described activity was initially developed for the Introductory College Level Experience in Microbiology (iCLEM) program, a research-based immersive laboratory course at the US Department of Energy Joint BioEnergy Institute. Originally designed as an accelerated program for high-potential, low-income, high school students (11th-12th grade), this curriculum could also be implemented for undergraduate coursework in a research-intensive laboratory course at a two- or four-year college or university.
              Cover page: Isolation and Characterization of Bacterial Cellulase Producers for Biomass Deconstruction: A Microbiology Laboratory Course
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