Dr. Block's laboratory is interested in effects of drugs, including anesthetics and drugs of abuse, on human cognition, brain structure, and regional cerebral blood flow. Current and past topics of research have included:
- Possible adverse effects of exposure to general anesthesia during infancy on childhood cognitive and CNS development
- Effects of chronic and acute effects of drugs of abuse, such as marijuana, on memory and other cognitive functions; and on cognition-related changes in regional cerebral blood flow, assessed by positron emission tomography and functional magnetic resonance imaging
- Awareness and learning during general anesthesia; and effects of general anesthesia on memory
- Effects of anesthetics (e.g., nitrous oxide) and anesthesia-related drugs (e.g., benzodiazepines) on memory and other cognitive functions.
1. Block RI, Thomas JJ, Bayman EO, Choi JY, Kimble KK, Todd MM: Are anesthesia and surgery during infancy associated with altered academic performance during childhood? Anesthesiology, 2012, 117, 494-503.
2. Jager G, Block RI, Luijten M, Ramsey NF: Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: A cross-sectional multicenter fMRI study. Journal of Psychoactive Drugs, 2013, 45, 156-167.
Uncontrolled pain continues to be a problem for patients. Pain management after surgery is one aspect of difficult to control acute pain. Because most pain models have not translated well to human postoperative pain, we have developed rodent models of postoperative pain undertaking a translational approach to acute pain mechanisms.
We have performed highly complementary behavioral, pharmacologic, neurochemical, and electrophysiological laboratory investigations of acute postoperative pain in the rodent.
Our focus is on mechanisms for peripheral sensitization caused by incisions. We have also established that the pharmacology of acute postoperative pain is unique and have identified novel therapies using spinal injections for its relief that can now be tested in humans. Our more recent efforts have been aimed toward determining the role of particular pain transmitting substances like lactic acid and nerve growth factor in deep tissues. We are using a variety of techniques to assay these pain mediators that may activate or sensitize nociceptors in several tissues. Primary afferent fiber recordings using in vitro skin nerve preparations and in vitro muscle nerve preparations.
Timothy J. Brennan, M.D., Ph.D.
Jun Ho Jang, Postdoctoral Research Scholar
Sinyoung Kang, Postdoctoral Research Scholar
Kanta Kido, Visiting Research Scholar
Alberto Subieta, Research Assistant II
Linjing Xu, Research Assistant III
The overall goal of our research is to gain a better understanding of the neuroanatomy, neurophysiology and neuropharmacology of the central nervous system pathways that convey pain, as well as the bulbospinal pathways that modulate the transmission of nociceptive information. Our studies emphasize a systems-level approach that uses many different methodologies in concert, including behavioral pharmacology in normal, transgenic or knockout animals, neuroanatomical tract tracing, immunocytochemical labeling of neurons, measurement of neurotransmitter release by push-pull perfusion or microdialysis, patch clamp recordings from neurons in slices of the spinal cord or brainstem and elementary molecular biology. We are particularly interested in the role that inhibitory neurotransmitters, such as gamma-aminobutyric acid (GABA) or the endogenous opioid peptides, play in the modulation of nociceptive sensitivity at the level of the spinal cord and brainstem. Our very early studies focused on how these neurotransmitter systems dictate responses to acute or transient nociception. Our current investigations focus on the role of these neurotransmitters in the response of the central nervous system to peripheral injury and the subsequent development of persistent pain. Our results indicate that persistent pain can lead to long-term changes in the pharmacology and physiology of both the afferent pathways that convey pain, as well as the efferent pathways that suppress pain. These changes have significant consequences for the ability of drugs to produce analgesia and for the body to invoke its own homeostatic mechanisms to control pain. The mechanisms that underlie the plasticity of central nervous system pathways in response to persistent neuropathic and inflammatory pain will continue to be a focus of our work in the future.
Donna L. Hammond, Ph.D.
Stephanie White, Research Assistant II
Marta Hamity, Postdoctoral Research Scholar
Liang Zhang, Assistant Research Scientist
Marlene Cano, MSTP Scholar/Trainee
Blanca Marquez de Prado, Research Investigator
Jeffrey Coble, MSTP Scholar/Trainee
Uche Maduka, Graduate Student
1. Zhang L, Hammond DL: Substance P enhances excitatory synaptic transmission to spinally projecting neurons in the rostral ventromedial medulla after inflammatory injury. J Neurophysiol. 102:1139-51, 2009. PubMed PMID: 19494188.
2. Jongeling AC, Johns ME, Murphy AZ, Hammond DL: Persistent inflammatory pain decreases the antinociceptive effects of the mu opioid receptor agonist DAMGO in the locus coeruleus of male rats. Neuropharmacology. 2009 May-Jun;56(6-7):1017-26. Epub 2009 Mar 3. PubMed PMID: 19265713; PubMed Central PMCID: PMC2680457.
4. Sykes KT, White SR, Hurley RW, Mizoguchi H, Tseng LF, Hammond DL: Mechanisms responsible for the enhanced antinociceptive effects of micro-opioid receptor agonists in the rostral ventromedial medulla of male rats with persistent inflammatory pain. J Pharmacol Exp Ther. 2007 Aug;322(2):813-21. Epub 2007 May 9. PubMed PMID: 17494863.
The major goal of our research is to better understand how severity of neurological disorders, such as epilepsy and pain syndromes, can be modified by genetic factors as well as external and internal environments. Using a versatile experimental model animal, the fruit fly Drosophila melanogaster, we are studying the effects of dietary modifications and genetic variations on severe seizure-like phenotypes displayed by mutants for the voltage-gated sodium channel gene. We are also interested in elucidating the role of steroid hormones in controlling behavior. We previously discovered that the insect steroid hormone ecdysone controls the internal physiological state in mature adult flies and has a significant impact on their memory, sleep and behavioral response to alcohol. Our current focus is on a novel G-protein-coupled receptor for ecdysone, which is a critical mediator of unconventional “nongenomic” steroid signaling, in the context of behavioral response to stress.
Toshihiro Kitamoto, Ph.D.
Junko Kasuya, Ph.D. Assistant Research Scientist
Hung-Lin Chen, Graduate Research Assistant
Arianna Lark, Graduate Research Assistant
Patrick Lansdon, Graduate Research Assistant
James Mrkvicka, Graduate Research Assistant
Morgan Lohr, Undergraduate Research Assistant
Katelyn Buhman, Undergraduate Research Assistant
Andrew Lilienthal, Undergraduate Research Assistant
3. Sakai T, Watanabe K, Ohashi H, Sato S, Inami S, Shimada N, Kitamoto T: Insulin-producing cells regulate the sexual receptivity through the painless TRP channel in Drosophila virgin females. PLOS One 2014; 9: e88175.
4. Ishimoto H, Wang Z, Rao, Y., Wu C-F, Kitamoto T: A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain. PLOS Genet 2013; 9:e1003843.
Division of Management Consulting
During the past 20 years, Franklin Dexter, MD PhD, and his colleagues have developed much of the science in anesthesia group and operating room management. Several times a year, he teaches a four-day intensive course in operating room management. Research projects include the following areas:
Increasing the productivity and efficiency of anesthesia and surgical practices;
Measuring managerial and clinical decision-making using survey and information systems data;
Quantifying the economic effect of anesthesia and surgical medications and devices;
Applying novel statistical methods to applications in anesthesia research.