Dr. Isabelle Decosterd
| PI of the laboratory: Isabelle Decosterd Tél: 021 692 52 69 Email: isabelle.decosterd@unil.ch Direct supervisor (assistant): Romain-Daniel Gosselin Tél: 021 692 52 54 Email: romain-daniel.gosselin@chuv.ch Department: Anesthesiology & DBCM Pain Research Unit Bugnon 9, CH-1005 Lausanne |
 |
Molecular mechanism of chronic pain
Description of Project:
The pain experience is the body’s alarm that triggers the appropriate protective responses. This dynamic feature is usually temporary and disappears after the healing of the injured region. Unfortunately, the effects of this warning system may persist long after the initial injury and the respective healing. In this case pain becomes chronic and results from a maladaptive response originated by molecular, cellular and structural modifications in the nervous system. Understanding the specific mechanisms of pain may be essential for the construction of a new approach for pain therapies in patients suffering from chronic pain.
Neuropathic pain is a form of chronic pain and occurs after an injury or dysfunction of the nervous system. This type of chronic pain is very difficult to treat with the actual therapies. We developed an animal model of neuropathic pain, called spared nerve injury model (SNI, 1 and 2) that lead to pain hypersensitivity mimicking pain symptoms in patients suffering from neuropathic pain. This exaggerated sensitivity is sustained by transcriptional changes in injured neurons as well as adjacent non-injured neurons (3). We recently have identified specific gene candidates in spinal cord receiving projections from both injured and non-injured population of small dorsal root ganglion (DRG) neurons (neurons responding to painful stimuli), combining laser capture microdissection (LCM) and Affymetrix microarray technologies (4).
Our ongoing work is focused on the validation of gene of interest from a set of genes we selected in our study. After familiarization with research context and the different techniques in our laboratory, the student will be involved in validation of our microarrays data by different approaches at the mRNA and protein levels. Compared to the project submitted for semester 1, the student will have the opportunity to explore more extensively one gene of interest and the underlying mechanisms associated.
Techniques used:
Real-Time PCR
Immunohistochemistry, in situ hybridization
Western Blots
Selected references:
(1) Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87: 149-58.
(2) Bourquin AF, Suveges M, Pertin M, Gilliard N, Sardy S, Davison AC, Spahn DR, Decosterd I (2006) Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse. Pain 122: 14.
(3) Pertin M, Ji RR, Berta T, Powell AJ, Karchewski L, Tate SN, Isom LL, Woolf CJ, Gilliard N, Spahn DR, Decosterd I (2005) Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons. J Neurosci 25: 10970-10980.
(4) Reilly SC, Cossins AR, Quinn JP, Sneddon LU (2004) Discovering genes: the use of microarrays and laser capture microdissection in pain research. Brain Res Brain Res Rev 46: 225-33.
Link to the group web site
