Dr. Block's laboratory is interested in effects of drugs, including anesthetics and drugs of abuse, on human cognition 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.
Robert Block, Ph.D.
Catherine Fruehling-Wall, Research Assistant I
Kay Kimble, Postdoctoral Research Assistant II
Barbara Wagoner, Research Assistant I
1. Block RI, O'Leary DS, Hichwa RD, Austinack JC, Boles Ponto LL, Ghoneim MM, Arndt S, Hurtig RR, Watkins GL, Hall JA, Nathan PE, Andreasen NC: Effects of frequent marijuana use on memory-related regional cerebral blood flow. Pharmacol Biochem Behav 72:237-50, 2002.
2. Block RI, O'Leary DS, Hichwa RD, Augustinack JC, Ponto LL, Ghoneim MM, Arndt S, Ehrhardt JC, Hurtig RR, Watkins GL, Hall JA, Nathan PE, Andreasen NC: Cerebral hypoactivity in frequent marijuana users. Neuroreport 11:749-53, 2000.
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
1. Kang S, Brennan TJ: Chemosensitivity and mechanosensitivity of nociceptors from incised rat hindpaw skin. Anesthesiology 111: 155-64, 2009.
2. Hamalainen MM, Subieta A, Arpey C, Brennan TJ: Differential effect of capsaicin treatment on pain-related behaviors after plantar incision. J Pain 10:637-645, 2009.
3. Wu C, Erickson MA, Xu J, Wild KD, Brennan TJ: Expression profile of nerve growth factor after muscle incision in the rat. Anesthesiology 110:140-149, 2009.
4. Banik RK, Brennan TJ: TRPV1 mediates spontaneous firing and heat sensitization of cutaneous sensory afferents after plantar incision. Pain 141:41-51, 2009.
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.
3. Price TJ, Cervero F, Gold MS, Hammond DL, Prescott SA: Chloride regulation in the pain pathway. Brain Res Rev. 2009 Apr;60(1):149-70. Epub 2008 Dec 31. PubMed PMID: 19167425.
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.
To gain insight into the basic neurobiological processes regulated by lithium―an effective drug for bipolar disorder and other neurological diseases—we used Affymetrix Genome Arrays to examine lithium-induced changes in genome-wide gene expression profiles of head mRNA from the genetic model organism Drosophila melanogaster. First, to identify the individual genes whose transcript levels are most significantly altered by lithium, we analyzed the microarray data with stringent criteria (fold change > 2 ; p <0.001) and evaluated the results by RT-PCR. This analysis identified 12 genes that encode proteins with various biological functions, including an enzyme responsible for amino acid metabolism and a putative amino acid transporter. Second, to uncover the biological pathways involved in lithium’s action in the nervous system, we used less stringent criteria (fold change >1.2 ; FDR <0.05) and assigned the identified 66 lithium-responsive genes to biological pathways using DAVID (Database for Annotation, Visualization and Integrated Discovery). The gene ontology categories most significantly affected by lithium were amino acid metabolic processes. Taken together, these data suggest that amino acid metabolism is important for lithium’s actions in the nervous system, and lay a foundation for future functional studies of lithium-responsive neurobiological processes using the versatile molecular and genetic tools that are available in Drosophila.
Toshihiro Kitamoto, Ph.D.
Benjamin Aldrich, Postdoctoral Research Scholar
Hiroshi Ishimoto, Postdoctoral Research Scholar
Ryan Jewell, Research Assistant I
Garrett Kaas, Graduate Research Assistant
Junko Kasuya, Assistant Research Scientist
1. Aldrich BT, Frakes EP, Kasuya J, Hammond DL, Kitamoto T: Changes in epxression of sensory organ-specific micro RNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation. Neuroscience 164:711-23, 2009.
2. Kasuya J, Ishimoto H, Kitamoto T: Neuronal mechanisms of learning and memory revealed by spatial and temporal suppression of neurotransmission using shibire, a temperature-sensitive dynamin mutant gene in Drosophila melanogaster. Front Mol Neurosci 2:11:1-6, 2009.
3. Aldrich BT, Kasuya J, Faron M, Ishimoto H, Kitamoto T: The amnesiac gene is involved in the regulation of thermal nociception in Drosophila melanogaster. J Neurogenetics, DOI: 10.3109/01677060903419751.
Our laboratory studies the molecular mechanisms involved in postoperative pain. Using an incisional model in rats, we have identified various genes in skin, muscle and dorsal root ganalia that are altered in the early, intermediate, and late postoperative period. These genes, acting alone or with other mediators, may be altering nociceptor phenotype, resulting in pain after incision. We are interested in understanding how these mediators act on nociceptors to enhance or prolong peripheral pain signals. Our long term goal is to develop new treatment strategies for postoperative pain control in patients having surgery.
Christina Spofford, M.D.
Shekher Mohan, Ph.D., Postdoctoral Research Scholar
1. Todd MM, Hindman BJ, Clarke WR, Torner JC, Weeks JB, Bayman EO, Shi Q, Spofford CM, and IHAST Investigators: Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 64:897–908, 2009.
2. Pulley S, Spofford CM, Brennan TJ: Continuous cervical paravertebral catheter knot. Journal of Clinical Anesthesia, In press.
3. Spofford CM: Local anesthetic toxicity during placement of peripheral nerve block. MedEdPORTAL; 2009. Available from: http://aamc.org/mededportal:ID=3161.
4. Spofford CM, Ashmawi H, Subieta A, Buevich F, Moses A, Brennan TJ: Ketoprofen produces modality specific inhibition of pain behaviors in rats after plantar incision. Anesth Analg 109:1992-9.