Brian M. Davis, PhD

Professor, Medicine, Neurobiology

Contact

E1457 Biomedical Science Tower
412-648-9745
F: 412-648-9731
bmd1@pitt.edu

Education

PhD, State University of New York at Stony Brook (1983)

Focus

Cellular and molecular mechanisms of central and peripheral nervous system development and plasticity.

Research Summary

The number one reason for doctor visits in the U.S. is ongoing somatic and visceral pain. This includes pain in the thorax, abdomen and pelvis. These pain sensations originate in peripheral tissues and are carried to the central nervous system via sensory neurons whose cell bodies are located in clusters called spinal or dorsal root ganglia. Sensory neurons are heterogeneous with respect to the type of sensation they detect, their anatomical properties and their role in generating pain signals. We need to need to be able to perceive pain so that we can be alerted to potentially damaging processes that might be occurring in our body. However, once the threat to proper function is detected, pain becomes a counterproductive sensation. In many cases, the pain persists even after the underlying cause has been resolved. This type of pathological pain is often due to changes in the sensory neurons themselves. Pathological changes in sensory neurons is thought to contribute to chronic pain associated with fibromyalgia, neuropathic pain, irritable bowel syndrome (IBS), pancreatitis, gastroesophageal reflux disease (GERD) and cancer. In addition to producing debilitating pain sensations, hyperactive sensory neurons can release bioactive peptides that further exacerbate disease. Recent studies suggest that dysfunctional sensory neurons may be an underlying cause of Type I diabetes and pancreatitis

The research in the Davis laboratory focuses on the role of growth factors in development and adult plasticity of the central and peripheral nervous system. This work is being conducted in collaboration with Dr. Kathryn Albers (Department of Medicine) who has created lines of transgenic mice overexpressing specific growth factors and Dr. H. Richard Koerber (Department of Neurobiology) who is examining plasticity of second order spinal cord neurons. Currently, our research is focused on somatic and visceral pain and the growth factors in the NGF and GDNF families. Specifically, we have found that these growth factors (that are required for embryonic development of primary afferents) are upregulated in models of chronic pain. We also have good evidence that this upregulation directly contributes to the development of persistent pain states. Our goal is to determine how these changes contribute to the development of chronic pain, with an emphasis on the transcriptional events and downstream signaling that controls the response properties of sensory neurons. Our hope is that this information will lead to identification of new targets that can be the basis of novel therapies for chronic somatic and visceral pain.

Publications

Malin S.A., Christianson, J.A., Bielefeldt, K. and Davis, B.M. TRPV1 expression defines functionally distinct colon afferents. J Neurosci 2009 (in press).

Fasanella, K.E., Christianson, J.A., Chanthaphavong, R.S. and Davis, B.M. Distribution and neurochemical identification of pancreatic afferents in the mouse. J. Comp. Neurol. 509:42-52, 2008.

Malin, S.A., Davis, B.M. and Molliver, D.C. Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc. 2(1): 152-60, 2007.

Malin, S.A., Molliver, D.C., Koerber, H.R., Cornett, P., Frye, R., Albers, K.M. and Davis, B.M. GDNF family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J. Neurosci. 26: 8588-8599, 2006.

Christianson, J.A., McIlwrath, S.L., Koerber, H.R. and Davis, B.M. Transient receptor potential vanilloid-1 immunopositive neurons are more prevalent within colon than skin or muscle sensory afferents. Neurosci. 140: 247-257, 2006

Christianson, J.A., Traub, R.J. and Davis, B.M. Differences in Spinal Distribution and 4Neurochemical Phenotype of Colonic Afferents in Mouse and Rat. J. Comp. Neurol. 494: 246-259, 2006.

Bielefeldt, K., Zhong, F., Koerber, H.R. and Davis, B.M. Phenotypic characterization of gastric sensory neurons in mice. Am J Physiol Gastrointest Liver Physiol 291: G987-997, 2006.