Nociceptive Screen

Coordinator:    Prof. Dr. Andreas Zimmer
Institution: Helmholtz Zentrum München
Chronic pain is one of the most common health problems, particularly in the elderly. In order to improve pain therapies and to develop novel analgesic medications, it is essential to obtain a better understanding of the still poorly understood pathomechanisms that contribute to chronic pain states. Genetic mouse models with interesting nociceptive phenotypes that we identify in the German Mouse Clinic can make an important contribution towards this goal. We have established a two-step procedure for the identification and characterization of such mouse lines. Mutants showing significantly enhanced or reduced pain responses are then further evaluated in more detailed assays in the Institute of the PI at the University of Bonn. In these test different pain modalities are evaluated, as well as inflammation-induced hyperalgesia and allodynia, and neuropathic pain.
One of our most interesting mouse line was the Sip1 line, with a heterozygous deletion of the gene encoding smad-interacting protein-1 (Sip1). Sip1 is a two-handed zink finger homeodomain-containing transcription factor, which is implicated in the aetiology of the Mowat-Wilson syndrome in humans. Sip1 is essential for the development of vagal neural crest cells in the mouse. We investigated heterozygous Sip1 mice, because homozygote Sip1 knockout mice are not viable. These mice exhibited a clear hypoalgesic phenotype. In our secondary screen we further refined the phenotype by conducting detailed behavioural, electrophysiological and immunohistochemical studies. Our data demonstrated that the Sip1 phenotype is caused by a modulation of neuronal development, which alters the peripheral sensitivity to thermal stimuli. Furthermore, our data clarified that patients suffering from Mowat-Wilson syndrome, show an under-reaction to pain, because they have a reduced pain sensitivity. These results were published in 2011 in “Pain” and in 2013 in “European Journal of Pain”.

     The Somatosensory System: Interphase between body and environment.
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