Peripheral and central processing of pain

Research interests in Dr. Koerber's laboratory include several projects designed to investigate the processing of somatosensory information following injury. These studies include examinations of plasticity in the processing of both tactile and pain information. Recent studies have documented compensatory reorganization of spinal networks following peripheral nerve injury and subsequent regeneration. These studies have demonstrated many aspects of synaptic reorganization, including reshaping of cutaneous receptive fields, alterations in synaptic efficacy and the formation of new functional connections between sensory fibers and dorsal horn neurons.

Ongoing experiments in the lab focus on plasticity in both primary sensory neurons and central spinal networks involved in pain pathways. Initial studies have quantitatively compared the properties of normal and post-injury cutaneous nociceptive sensory neurons. Results of these studies demonstrate that specific types of nociceptive sensory neurons demonstrate differing degrees of sensitization commensurate with the type of injury. Parallel studies using genetically-altered animals have assessed the roles that specific neurotrophins and/or the GDNF family of neurotrophic factors may play in this process. The aims of future studies are to determine how changes in the expression of these growth factors in the skin following injury can lead to changes in afferent fiber sensitivity. Possible mechanisms for this sensitization include modulating the expression of mechanically and thermally sensitive ion channels (e.g. ASIC and TRP channels) and G-protein coupled receptors (P2Y1 and Mrgprd). In addition to genetically altered mice, more recent projects employ a novel in vivo siRNA strategy that allows for the investigation of the potential roles of specific channels and receptors at the molecular level.

Trainees in Dr. Koerber's laboratory have the opportunity to learn a variety of neurophysiological, neuroanatomical, behavioral, and molecular biological techniques. These techniques allow for a robust examination of the response characteristics of the adult and developing nervous system to injury.

Sample Pulbications:

The functional organization of cutaneous low-threshold mechanosensory neurons.
Li L, Rutlin M, Abraira VE, Cassidy C, Kus L, Gong S, Jankowski MP, Luo W, Heintz N, Koerber HR, Woodbury CJ, Ginty DD.
Cell. 2011 Dec 23;147(7):1615-27.

Purinergic receptor P2Y1 regulates polymodal C-fiber thermal thresholds and sensory neuron phenotypic switching during peripheral inflammation.
Jankowski MP, Rau KK, Soneji DJ, Ekmann KM, Anderson CE, Molliver DC, Koerber HR.
Pain. 2012 Feb;153(2):410-9.

Neurotrophic Factors and Nociceptor Sensitization.
Jankowski MP, Koerber HR.
In: Kruger L, Light AR, editors. Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press; 2010. Chapter 2.

The ADP receptor P2Y1 is necessary for normal thermal sensitivity in cutaneous polymodal nociceptors.
Molliver DC, Rau KK, McIlwrath SL, Jankowski MP, Koerber HR.
Mol Pain. 2011 Feb 10;7:13.

Enhanced artemin/GFRα3 levels regulate mechanically insensitive, heat-sensitive C-fiber recruitment after axotomy and regeneration.
Jankowski MP, Rau KK, Soneji DJ, Anderson CE, Koerber HR.
J Neurosci. 2010 Dec 1;30(48):16272-83.

Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers.
Koerber HR, McIlwrath SL, Lawson JJ, Malin SA, Anderson CE, Jankowski MP, Davis BM.
Mol Pain. 2010 Sep 21;6:58.

Mrgprd enhances excitability in specific populations of cutaneous murine polymodal nociceptors.
Rau KK, McIlwrath SL, Wang H, Lawson JJ, Jankowski MP, Zylka MJ, Anderson DJ, Koerber HR.
J Neurosci. 2009 Jul 1;29(26):8612-9.

Sensitization of cutaneous nociceptors after nerve transection and regeneration: possible role of target-derived neurotrophic factor signaling.
Jankowski MP, Lawson JJ, McIlwrath SL, Rau KK, Anderson CE, Albers KM, Koerber HR.
J Neurosci. 2009 Feb 11;29(6):1636-47.

Identity of myelinated cutaneous sensory neurons projecting to nocireceptive laminae following nerve injury in adult mice.
Woodbury CJ, Kullmann FA, McIlwrath SL, Koerber HR.
J Comp Neurol. 2008 May 20;508(3):500-9.

Overexpression of neurotrophin-3 enhances the mechanical response properties of slowly adapting type 1 afferents and myelinated nociceptors.
McIlwrath SL, Lawson JJ, Anderson CE, Albers KM, Koerber HR.
Eur J Neurosci. 2007 Oct;26(7):1801-12.

TRPV1 Unlike TRPV2 Is Restricted to a Subset of Mechanically Insensitive Cutaneous Nociceptors Responding to Heat.
Lawson JJ, McIlwrath SL, Woodbury CJ, Davis BM, Koerber HR.
J Pain. 9: 298-308, 2008.

Synaptic Plasticity in the Adult Spinal Dorsal Horn: The Appearance of New Functional Connections Following Peripheral Nerve Regeneration.
Koerber, HR, Mirnics, K and Lawson, JJ.
Exp. Neurol. 200:468-479, 2006.

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