Department of Anesthesiology & Perioperative Care: School of Medicine: University of California, Irvine

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Basic Science & Translational Research

Baisc and Translational Research

Professors within the Department of Anesthesiology & Perioperative oversee several laboratories throughout UC Irvine and its affiliates. Our Department is committed to research excellence and has dedicated an immense amount of time and resources that advance our understanding of anesthesia and the brain, pain pathways and spinal cord injury.

Areas of Interests

Genetics and Spinal Control of Pain Perception

Z. David Luo, MD, PhD research interests focus on molecular mechanisms of chronic pain. Dr. Luo and his team are studying how chronic pain inducing conditions, such as peripheral nerve injury, bone cancer and spinal cord injury, induce changes in gene expression in sensory pathways that lead to changes in pain perception.

Two approaches are utilized in Dr. Luo’s research. First, they use gene chip analysis to compare gene expression profiles between control and experimental tissue samples, taken from pathological conditions associated with abnormal sensations, to identify genes that may be the molecular determinants of specific nociceptive states and serve as targets for the development of more specific and safer analgesics.

Their second approach is to study how altered target gene expression contributes to spinal sensitization, a central mechanism of abnormal sensations. Briefly, they use behavioral pharmacology, cellular and molecular biology and immunohistochemistry techniques to study how these genes are regulated under pain-inducing conditions, and how these changes contribute to abnormal sensation development and maintenance. Finally, Dr. Luo’s team is developing and validating novel interventions for chronic pain management.

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Publications

  • Guo Y, Zhang Z, Wu HE, Luo ZD, Hogan QH, Pan B. Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons. Neuropharmacology. 2017 May 1;117:292-304. doi: 10.1016/j.neuropharm.2017.02.019. Epub 2017 Feb 22.
  • Faria LC, Gu F, Parada I, Barres B, Luo ZD, Prince DA. Epileptiform activity and behavioral arrests in mice overexpressing the calcium channel subunit α2δ-1. Neurobiol Dis. 2017 Jun;102:70-80. doi: 10.1016/j.nbd.2017.01.009. Epub 2017 Feb 11.
  • Sun Y, Ikrar T, Davis MF, Gong N, Zheng X, Luo ZD, Lai C, Mei L, Holmes TC, Gandhi SP, Xu X. Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity. Neuron. 2016 Oct 5;92(1):160-173. doi: 10.1016/j.neuron.2016.08.033. Epub 2016 Sep 15.
  • Pan B, Guo Y, Wu HE, Park J, Trinh VN, Luo ZD, Hogan QH. Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury. Pain. 2016 Sep;157(9):2068-80. doi: 10.1097/j.pain.0000000000000612.
  • Park J, Trinh VN, Sears-Kraxberger I, Li KW, Steward O, Luo ZD. Synaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injury. J Comp Neurol. 2016 Feb 1;524(2):309-22. doi: 10.1002/cne.23844. Epub 2015 Jul 16.

Addiction and Behavioral Pathology

Sean Ostlund, MD and his research team investigate neural mechanisms of decision making and motivated behavior, including how chronic drug use impacts the brain to support pathological drug-seeking behavior. A multidisciplinary approach is applied to measure and manipulate the activity of genetically and anatomically targeted neural circuits in rodents performing sophisticated behavioral tasks. Determining how ascending dopamine systems contribute to behavior is a major area of study in the lab. Fast-scan cyclic voltammetry and microdialysis are used to characterize distinct aspects of dopamine signaling to determine their relationship to learning and behavior and how this is altered in addiction and other pathological states. A range of strategies, including chemo and optogenetic tools, is used to selectively perturb the function of dopamine and other neurochemical signaling pathways to determine their specific contributions to behavior.

Related Links

Publications

  • Ostlund SB, Liu AT, Wassum KM, Maidment NT. Modulation of cue-triggered reward seeking by cholinergic signaling in the dorsomedial striatum. Eur J Neurosci. 2017 Feb;45(3):358-364. doi: 10.1111/ejn.13462. Epub 2016 Nov 21.
  • Collins AL, Aitken TJ, Greenfield VY, Ostlund SB, Wassum KM. Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation. Neuropsychopharmacology. 2016 Nov;41(12):2830-2838. doi: 10.1038/npp.2016.81. Epub 2016 May 31.
  • Halbout B, Liu AT, Ostlund SB. A Closer Look at the Effects of Repeated Cocaine Exposure on Adaptive Decision-Making under Conditions That Promote Goal-Directed Control. Front Psychiatry. 2016 Mar 21;7:44. doi: 10.3389/fpsyt.2016.00044. eCollection 2016.
  • Wassum KM, Greenfield VY, Linker KE, Maidment NT, Ostlund SB. Inflated reward value in early opiate withdrawal. Addict Biol. 2016 Mar;21(2):221-33. doi: 10.1111/adb.12172. Epub 2014 Jul 31
  • Mendez IA, Ostlund SB, Maidment NT, Murphy NP. Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity. Neuropsychopharmacology. 2015 Aug;40(9):2103-12. doi: 10.1038/npp.2015.67. Epub 2015 Mar 10.

Neuroimaging, Consciousness, & Anesthesia

Michael Alkire, MD and his lab work to investigate the mechanisms of anesthetic action on learning, memory, consciousness and pain processing. Neuroimaging technologies such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG), as well as small animal experimentation are used to identify and experimentally manipulate various key sites of anesthetic action in the brain. Dr. Alkire is the principle investigator on several grants to further this end.

Using brain imaging as a tool to understand anesthetic-induced unconsciousness, Dr. Alkire brings an international reputation to the Department of Anesthesiology & Perioperative Care. He has discovered that intra-thalamic microinfusions of nicotine blocks the unconsciousness producing aspect of anesthesia and allows an animal to wake up and move around within a chamber filled with anesthetic.