Christian Brenneis, PhD
Background and Research Interests
I obtained my PhD at the Goethe University in Frankfurt, Germany specializing on lipid signaling during chronic pain. During that time I developed understandings how the synthesis of prostanoids, epoxyeicosatrienoic acids (EETs) and sphingolipids is regulated during inflammation and how these molecules mediate hyperalgesia by sensitizing primary afferent and spinal cord neurons or by regulating innate immune responses from spinal microglia (Brenneis et al., 2006; Brenneis et al., 2008; Coste et al., 2008).
In June 2009 I joined Clifford Woolf’s lab where I now perform experiments using cellular imaging, behavioral tests and analytical approaches which are part of the following projects:
1. Functional phenotyping of nociceptors by selective silencing via TRP-mediated entry of impermeant sodium channel blockers. We aim to block specific subsets of neurons expressing a certain type of cation channels by introducing the permanently charged sodium channel blocker QX-314 through the channel pore (Binshtok et al., 2007). By testing the nociceptive behavior of animals treated with QX-314 and a selective agonist I plan to characterize the function of these silenced neuron populations for the perception of different sensations like heat, cold or mechanical stimulation.
2. Improving pain selective anesthesia with QX-314 and different caine-type local anesthetics. Lidocaine acts as a TRP-agonist and can thereby could help charged QX-314 entering nociceptive neurons (Leffler et al., 2008). A combination of lidocaine and QX-314 produces long lasting and for a certain time period also pain selective analgesia (Gerner et al., 2008). I now aim to extend this approach and test most caine-type local anesthetics for their ability to activate large pore cation channels in sensory neurons. Follow up studies will test if this TRP activation correlates with the pain block induced by a QX-314 - caine combination.
3. Developing human stem cell derived sensory neurons. Sensory neurons which are used in research are usually obtained from rodent dorsal root ganglia. However, those cells have different characteristics compared to human sensory cells and the very low cell numbers which are obtained make large drug screens difficult. In collaboration with Prof. Lee Rubin form Harvard Stem Cell Institute and Prof. Quifu Ma from Dana Faber Cancer Research Center we try to differentiate human stem cells into functional nociceptors. Currently I support electrophysiology done by Brian Wainger with cellular imaging to functionally characterize sensory specific channels in potential human nociceptors.
Binshtok AM, Bean BP, Woolf CJ (2007) Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 449:607-610.
Brenneis C, Maier TJ, Schmidt R, Hofacker A, Zulauf L, Jakobsson PJ, Scholich K, Geisslinger G (2006) Inhibition of prostaglandin E2 synthesis by SC-560 is independent of cyclooxygenase 1 inhibition. FASEB J 20:1352-1360.
Brenneis C, Coste O, Schmidt R, Angioni C, Popp L, Nusing RM, Becker W, Scholich K, Geisslinger G (2008) Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice. J Cell Mol Med 12:639-648.
Coste O, Brenneis C, Linke B, Pierre S, Maeurer C, Becker W, Schmidt H, Gao W, Geisslinger G, Scholich K (2008) Sphingosine 1-phosphate modulates spinal nociceptive processing. J Biol Chem 283:32442-32451.
Gerner P, Binshtok AM, Wang CF, Hevelone ND, Bean BP, Woolf CJ, Wang GK (2008) Capsaicin combined with local anesthetics preferentially prolongs sensory/nociceptive block in rat sciatic nerve. Anesthesiology 109:872-878.
Leffler A, Fischer MJ, Rehner D, Kienel S, Kistner K, Sauer SK, Gavva NR, Reeh PW, Nau C (2008) The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. J Clin Invest 118:763-776.