SP 6
Prof. Dr. rer. nat. Andreas Zimmer
Institute of Molecular Psychiatry
University of Bonn
Sigmund-Freud-Str. 25,
53127 Bonn
Phone: +49 (0)228 6885-300
Fax: +49 (0)228 6885-301
E-mail: a.zimmer@uni-bonn.de
Homepage of the Institute of Molecular Psychiatry
CV Zimmer
(219KB)
The role of the CB2 receptor and human CB2 receptor variants in neuropathic pain
The role of the CB2 receptor in neuroinflammation and the functional relevance of human receptor variants is the focus of SP6. We replicated our original observation in a French sample of osteoporotic patients that a Gln63Arg variant is associated with low bone mass using a Chuvashian family sample. This study strongly supports the notion that the two human CB2 receptor variants have distinct functional properties. We have therefore started to develop “humanized” knock-in mouse strains where the mouse CB2 receptor was replaced by the human variants. Another important novel genetic tool that we have generated is a floxed Cnr2 knockout strain.
Also in SP6, we found evidence that CB2 receptor-mediated endocannabinoid signaling contributes to a regional containment of neuropathic pain responses. Thus, hyperalgesia and allodynia after partial ligation of the sciatic nerve developed only close to site of the nerve injury in wild type mice, while CB2 receptor knockout mice also showed enhanced pain sensitivity on the contralateral side, which is probably caused by enhanced INF-γ response in the absence of CB2 receptor signaling.
Now we will first clarify dynamic changes in the ECS during the development of neuropathic pain in different cells of dorsal root ganglia and the spinal cord. We will then use novel microglia, astrocyte and neuron-specific CB2 knockout models established in the first funding period to specifically address the contribution of these cells to the modulation of neuropathic pain responses. To determine whether neuropathic pain responses are differentially modulated by functionally distinct human CB2 receptor variants, we will also investigate mouse strains with “humanized” CB2 receptors. The analysis of these novel mouse strains will involve the determination of the nociceptive phenotypes of these strains, particularly in animal models of neuropathic pain, as well as investigations of the molecular signature associated with neuropathic pain conditions.
Team members:
Elisa Nent, PhD student
Phone: +49 (0)228 6885-314
Fax: +49 (0)228 6885-301
E-mail: st6elnent@uni-bonn.de
Chihiro Nozaki, PhD
Phone: +49 (0)228 6885-310
Fax: +49 (0)228 6885-301
E-mail: chihiron@uni-bonn.de
David-Marian Otte, PhD
Phone: +49 (0)228 6885-331
Fax: +49 (0)228 6885-301
E-mail: d.otte@uni-bonn.de
Alexandra Wojtalla, PhD
Phone: +49 (0)228 6885-328
Fax: +49 (0)228 6885-301
E-mail: wojtalla@uni-bonn.de