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Institute of Pharmacology

Conditional deletion of genes encoding pain-relevant proteins in peripheral nociceptive neurons

We use the Cre/loxP system for conditional gene deletion in specific anatomical compartments of the pain pathway. For example, we have generated a mouse line which enables deletion of genes specifically in all nociceptive neurons of the dorsal root ganglia (DRG) and trigeminal ganglia without affecting gene expression in non-nociceptive neurons, the spinal cord, the brain or any other organs in the body (Agarwal et al., Genesis 2004). We have made these mice widely available to the pain community to enable nociceptor-specific deletion of a variety of pain-related genes. Recently, we have also developed viral-based or transgenic approaches to enable site-specific manipulation of genes in the spinal dorsal horn (Tappe et al., Nature Medicine 2006), in noradrenergic neurons of the Locus ceruleus (an important pain-modulatory center) or in subtypes of peripheral nociceptors.

 

Specific deletion of targeted proteins from nociceptive neurons in the dorsal root ganglia achieved using SNS-Cre mice

 

 

 

Several ongoing projects in the lab involve conditional deletion of receptors for neurotransmitters and neuromodulators such as cannabinoids, GABA, glutamate, endothelin-1 etc. or their signaling effectors such as G-proteins, protein kinases etc. selectively in nociceptive neurons. Currently, we are analysing the contribution of these mediators in inflammatory and neuropathic pain models using behavioural, electrophysiological and biochemical methods. For example, we found recently that a nociceptor-specific deletion of cannabinoid receptor 1 abrogates a large proportion of analgesia mediated by endocannabinoids and therapeutic cannabinoids. Our current focus on peripheral mechanisms of pain is based upon the hope of being able to target pain while circumventing centrally-mediated cognitive, motor and emotional side-effects. This work is partly funded by the Clinical Research Group 107 of the DFG.


Group members involved: Anke Tappe-Theodor, Bettina Hartmann, Ceng Luo, Gurpreet Kaur Satagopam, Peter Lepczynski, Hans-Joseph Wrede, Dunja Baumgärtl-Ahlert