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Our lab is interested in the molecular mechanisms of sensory neuron plasticity after peripheral injuries. We have two main focuses: peripheral mechanisms of musculoskeletal pain specifically in the context of ischemia and the developmental sensitization of sensory afferents.
We know that chronic limb ischemia is a major health issue that affects a large number of people and is a result of numerous cardiovascular diseases and traumas. A serious side effect of limb ischemia is peripheral muscle damage and as result of this damage, many patients with limb ischemia experience altered cardiovascular reflexes and musculoskeletal pain. Chronic pain in children however can arise from multiple sources including surgery, inflammatory disorders or even when in neonatal intensive care. While we do know a great deal of information about the role of nociceptors to the development of pain states, we do not have a comprehensive understanding of all subtypes of sensory fibers after ischemic muscle injury, during development or after neonatal injuries which may alter the function of sensory neurons into adulthood.
In order to increase our knowledge of these fibers, we utilize several ex vivo recording preparations that enable us to comprehensively phenotype cutaneous and muscle afferent fibers before and after peripheral injuries in neonatal and adult mice. In addition to electrophysiological recording, we also utilize a variety of other molecular (RNA interference, realtime RT-PCR, single cell PCR, single cell microarray, western blotting), anatomical (immunocytochemistry, fluorescence and confocal microscopy, electron microscopy) and in vitro (primary neuron and heterologous cell cultures, second messenger signaling) techniques to obtain a broad understanding of pain development at the primary afferent level.
These studies will hopefully lead to the development of treatments for adverse changes in cardiovascular reflexes or chronic musculoskeletal pain associated with limb ischemia and will generate novel information on the development of both nociceptive and non-nociceptive afferents.
Li, L., Rutlin, M., Abraira, V., Cassidy, C., Jankowski, M.P., Luo, W., Heintz, N., Koerber, H.R., Woodbury, C.J., and Ginty, D.D. The functional organization of cutaneous low-threshold mechanosensory neurons. Cell. 147: 1615-27. 2011.
Molliver, D.C., Rau, K.K., McIlwrath, S.L., Jankowski, M.P., and Koerber, H.R. The ADP receptor P2Y1 is necessary for normal thermal sensitivity in cutaneous polymodal nociceptors. Mol. Pain. 7: 13. 2011.
Koerber, H.R., McIlwrath, S.L., Lawson, J.J.., Malin, S.A., Anderson, C.E., Jankowski, M.P., and Davis, B.M. Mouse cutaneous C-fibers lacking TRPV1 are sensitized to heat following peripheral inflammation. Molecular Pain. 6: 58. 2010.
Jankowski, M.P., Rau, K.K., Soneji, D.J., Anderson, C.E., and Koerber, H.R. Enhanced artemin/GFRa3 levels regulate mechanically insensitive, heat sensitive C-fiber recruitment after axotomy and regeneration. J. Neurosci. 30: 16272-83. 2010.
Rau, K.K., McIlwrath, S.L., Wang, H., Lawson, J.J., Jankowski, M.P., Zylka, M.J., Anderson, D.J., and Koerber, H.R. Mrgprd enhances excitability in specific populations of cutaneous murine polymodal nociceptors. J. Neurosci. 29: 8612-9. 2009.
Jankowski, M.P., McIlwrath, S.L., Cornuet, P.K., Jing X, Salerno K.M., Koerber, H.R., and Albers, K.M. Sox11 transcription factor regulates peripheral nerve regeneration in the adult. Brain Res. 1256: 43-54. 2009.
Jankowski, M.P., Lawson, J.J., McIlwrath, S.L., Rau, K.K., Anderson, C.E., Albers, K. M., and Koerber, H.R. Sensitization of cutaneous nociceptors following nerve transection and regeneration: Possible role of target derived neurotrophic factor signaling. J. Neurosci. 29: 1636-47. 2009.
Jankowski, M.P. and Koerber, H.R. Neurotrophic Factors and Nociceptor Sensitization. In Translational Pain Research: From Mice to Men. Eds.: Kruger and Light, CRC Press. 31-50. 2009.
Michael P. Jankowski, PhD.
Assistant ProfessorDepartment of Anesthesia, Division of Pain ManagementDepartment of PediatricsCincinnati Children’s Hospital Medical Center3333 Burnet AveMLC 2001Cincinnati, OH 45229
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