Neurobiology and Pain Therapeutics, DIR
NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 49 ROOM 1A04
49 CONVENT DR, MSC 4410
BETHESDA, MD 20892-4410
Phone: (301)496-2758
Fax: (301)402-0667
E-mail: michael.iadarola@nih.gov
Research Interests
Our research program addresses basic molecular and physiological mechanisms of pain transmission and pain control in the spinal cord and brain. The dorsal spinal cord contains the first set of synaptic contacts that process and relay incoming nociceptive (pain) information. Our research has identified the dorsal spinal cord as a locus of neuronal plasticity and altered gene expression in persistent pain states. Molecular biological studies are aimed at (a) elucidating mechanisms of stimulus-transcription coupling and gene regulation, (b) identifying, via subtraction cloning, genes whose expression is increased by nociceptive stimuli and (c) investigating novel pharmacological and gene transfer-based approaches to pain treatment since pain is effectively controlled at the spinal cord level. Physiological studies in brain investigate mechanisms of acute and chronic pain in human subjects using in vivo functional brain imaging techniques.
Education
B.S. (Biology) American University 1973
Ph.D.(Pharmocology) Georgetown University School of Medicine 1980
Investigator Biosketch
Michael J. Iadarola, Ph.D. Senior Investigator and Chief, Integrative Neurobiology and Neuronal Gene Expression Unit , NIDCR. Dr. Iadarola received his Ph.D. from the Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C., where he studied the mechanisms of epilepsy and seizure control through the inhibitory amino acid transmitter GABA with Dr. Karen Gale. Epilepsy research was continued in the in vitro hippocampal slice using electrophysiological methods at Duke University with Dr. W. A. Wilson. Dr. Iadarola subsequently obtained a Pharmacology Research Associate Trainee fellowship with the NIGMS and worked at the NIMH with Drs. Erminio Costa and Hsiu-Ying T. Yang on the molecular regulation of opioid neuropeptides. There he discovered that persistent pain up-regulated dynorphin opioid gene expression in the pain processing laminae of the spinal cord dorsal horn. He is currently the Chief of the Neuronal Gene Expression Unit. His laboratory studies the molecular biology of pain and pain control systems mainly in the dorsal root ganglion and the first synaptic connection in the spinal cord. The laboratory investigates (a) synaptic plasticity in the dorsal spinal cord using subtraction cloning and differential expression profiling, (b) the molecular function of pain-transducing molecules in peripheral nerve endings, in particular the vanilloid receptor 1 (VR1), and (c) new treatment strategies for the control of severe intractable pain. The novel approaches to pain control include selective pain cell deletion, pre-emptive analgesia, and the use of viral vectors for in vivo gene transfer for the expression of therapeutic bio-molecules.
Recent publications
Saka E, Harlan P, Fitzgerald DJ, Iadarola MJ, Graybiel AM. Ablation of cholingeric and somatostatinergic interneurons in the striatum by substance P-linked pseudomonas exotoxin (SP-PE) leads to changes in striosome-matrix excitability. Proc Natl Acad Sci USA, (in press).
Rosier E, Iadarola MJ, Coghill RC. Reproducibility of pain measurement and pain perception. Pain, 2002 (in press).
Olah Z, Karai L, Iadarola MJ. Protein kinase Ca required for vanilloid receptor 1 activation: Evidence for multiple signalling pathways. J Biol Chem 2002, (in press).
Benoliel R, Eliav E, Iadarola MJ. Neuropeptide Y in trigeminal ganglion following chronic constriction injury of the rat infraorbital nerve: is there correlation to somatosensory parameters? Pain 2001;91:111-21.
Caudle RM, Mannes AJ, Benoliel R, Eliav E, Iadarola MJ. Intrathecally administered cholera toxin blocks allodynia and hyperalgesia in persistent pain models. J Pain 2001;2:118-27.
Coghill RC, Gilron I, Iadarola MJ. Hemispheric lateralization of somatosensory processing. J Neurophysiol 2001;85:2602-12.
Finegold AA, Perez F, Iadarola MJ. Antisense knock-down of NMDA receptors by gene transfer to motor neurons in vivo. Molec Brain Res 2001;90:17-25.
Kedei N, Szabo T, Lile JD, Treanor JJ, Olah Z, Iadarola MJ, Blumberg PM. Analysis of the native quaternary structure of vanilloid receptor 1. J Biol Chem 2001;276:28613-19.
Yang HYT, Wilkening S, Iadarola MJ. Spinal cord genes enriched in dorsal horn and induced by noxious stimulation identified by subtraction cloning and differential hybridization. Neuroscience 2001;103:493-502.
Benoliel R, Tanaka M, Caudle RM, Iadarola MJ. Co-localization of NMDA receptors and substance P receptors in rat spinal cord. Neuroscience Letts 2000;291:61-64.
Byers MR, Chudler EH, Iadarola MJ: Chronic tooth pulp inflammation causes transient andpersistent expression of Fos in dynorphin-rich regions of rat brain stem. Brain Res 2000;861:191-207.
Iadarola MJ, Coghill RC. Imaging of pain: recent developments. Curr Opin Anesthesiology 1999; 12:583-589.
Iadarola MJ, Berman KF, Zeffiro TA, Byas-Smith MG, Gracely RH, Max MB, Bennett GJ. Activation of multiple neural networks during acute pain and allodynia evoked by capsaicin assessed with positron emission tomography. Brain 1998;121:931-47.