Prof. Dr. Dr. Gerd Geisslinger

Institut für Klinische Pharmakologie
Theodor Stern Kai 7
60590 Frankfurt

Tel +49-69-6301-7619
Fax +49-69-6301-7617

geisslingerem.uni-frankfurt.de

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Scientific Focus

Neurobiology and Neuropharmacology of pain and inflammation
Identification of new targets for the treatment of pain
Anti-tumor effects of analgesics
Investigation of platelet function and haemostasis

Methods

Laboratory methods:

* Mass-spectrometry: LC/MS/MS with protein analytics option (QTrap), GC, HPLC
* Real-time PCR (Taqman, LightCycler)
* Identification of genetic polymorphisms (Pyrosequencing, LightCycler)
* DNA sequencing, cloning, transfection, transformation
* RNase protection assay
* In-situ hybridization
* 2D gel electrophoresis
* Yeast-Two-Hybrid System
* Immunohistochemistry
* Flow cytometry (FACS)
* Patchclamp technique
* Calcium imaging

Animal models:

* Animal models of pain: Formalin test, Hot-plate test, inflammatory hyperalgesia, paw oedema (plethysmometry), models of neuropathic pain
* In vivo tumor models
* Functional knockdown using Antisense Oligonucleotides
* Implantation of intrathecal catheters for drug administration into the lumbar spinal cord
* Implantation of osmotic mini pumps for the continuous delivery of drugs

Human pain models:

* Chemical pain: CO2-stimulation with evoked cortical potentials
* Thermal-chemical pain: Heat-Capsaicin model
* Inflammatory pain: „Freeze Lesion“, tonic-nasal pain
* Electrical pain: Sinus wave model
* Mechanical pain: blunt pressure, punctuated pain
* muscle hyperalgesia induced by muscle contractions (DOMS model)

Other Methods:

* Microdialysis for the assessment of drug concentrations in peripheral tissues
* Pharmacokinetic calculations, Pharmacokinetic-Pharmacodynamic modelling

Selected Publications

# Lötsch J and Geisslinger G. Are mu-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol Med 2005 Feb;11(2):82-9.

# Burian M, Geisslinger G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacology & Therapeutics 2005, Aug;107(2):139-54

# Maier T, Janssen A, Schmidt R, Geisslinger G, and Grösch S. Targeting the beta-catenin/APC pathway: a novel mechanism to explain the Cyclooxygenase-2-independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Faseb J. 2005 Jun 9

# Schmidtko A, Del Turco D, Coste O, Ehnert C, Niederberger E, Ruth P, Deller T, Geisslinger G, Tegeder I. Essential role of the synaptic vesicle protein synapsin II in formalin-induced hyperalgesia and glutamate release in the spinal cord. Pain. 2005 May;115(1-2):171-81.

# Lötsch J, Skarke C, Schneider A, Hummel T, and Geisslinger G. The 5 HT4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression. Clin Pharmacol Ther 2005 Sep;78(3):278-87

# Skarke C, Geisslinger G, Lötsch J. Is Morphine-3-Glucuronide of Therapeutic Relevance? Pain 2005 Aug;116(3):177-80

# Nüsing RM, Treude A, Weissenberger C, Jensen B, Bek M, Wagner C, Narumiya S, Seyberth HW. Dominant Role of Prostaglandin E2 EP4 Receptor in Furosemide-Induced Salt-Losing Tubulopathy: A Model for Hyperprostaglandin E Syndrome/Antenatal Bartter Syndrome. J Am Soc Nephrol. 2005 Aug;16(8):2354-62

# Graff J, Harder S, Wahl O, Scheuermann EH, Gossmann J. Anti-inflammatory effects of clopidogrel intake in renal transplant patients: effects on platelet-leukocyte interactions, platelet CD40 ligand expression and pro-inflammatory biomarkers. Clin Pharmacol Ther 2005 Nov;78(5):468-76

# Hofacker A, Coste O, Nguyen H, Marian C, Scholich K, Geisslinger G. Downregulation of the cytosolic prostaglandin E2 synthase results in decreased nociceptive behavior in rats. J. Neurosci. 2005 Sep 28;25(39):9005-9

# Tegeder I and Geisslinger G. Opioids as modulators of cell death and survival – unraveling mechanisms and revealing new indications. Pharmacological Reviews 2004 Sep;56(3):351-69

# Kunz S, Niederberger E, Ehnert C, Coste O, Pfenninger A, Kruip J, Wendrich TM, Schmidtko A, Tegeder I, Geisslinger G. The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain (NFL) breakdown in the spinal cord and reduces thermal hyperalgesia. Pain 2004 Jul;110(1-2):409-18

# Pierre SC, Hausler J, Birod K, Geisslinger G, Scholich K. PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate. EMBO J. 2004 Aug 4;23(15):3031-40

# Tegeder I, Del Turco D, Schmidtko A, Sausbier M, Feil R, Hofmann F, Deller T, Ruth P, and Geisslinger G. Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase-I. PNAS 2004 Mar2;101(9):3253-7

# Burian M, Tegeder I, Seegel M, and Geisslinger G. Peripheral and Central Antihyperalgesic Effects of Diclofenac in a Model of Human Inflammatory Pain. Clin Pharmacol Ther 2003 Aug;74(2):113-20

# Grösch S, Tegeder I, Schilling K, Maier T, Niederberger E, and Geisslinger G. Activation of c-Jun-N-terminal-kinase is crucial for the induction of a cell cycle arrest in human colon carcinoma cells caused by flurbiprofen enantiomers. FASEB J 2003 Jul;17(10):1316-8

# Tegeder I, Grösch S, Schmidtko A, Häussler A, Schmidt H, Niederberger E, Scholich K, and Geisslinger G. G-protein independent G1-cell cycle block and apoptosis with morphine in adenocarcinoma cells – involvement of p53 phosphorylation. Cancer Res 2003 Apr 15;63(8):1846-52

# Tegeder I, Meier S, Burian M, Schmidt H, Geisslinger G, and Lötsch J. Peripheral opioid analgesia in experimental human pain models. Brain 2003 May;126(Pt 5):1092-10

# Niederberger E, Schmidtko A, Rothstein JD, Geisslinger G, and Tegeder I. Modulation of spinal nociceptive processing through the glutamate transporter GLT-1. Neuroscience 2003, 116, 81-87

# Skarke C, Darimont J, Schmidt H, Geisslinger G, and Lötsch J. Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. Clin Pharmacol Ther 2003 Jan;73(1):107-121

# Lötsch J, Skarke C, Grösch S, Darimont J, Schmidt H, and Geisslinger G. The polymorphism A118G of the human mu-opioid receptor gene decreases the clinical activity of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 2002 Jan;12(1):3-9

# Niederberger E, Tegeder I, Vetter G, Schmidtko A, Schmidt H, Euchenhofer C, Bräutigam L, Grösch S, and Geisslinger G. Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-kappaB. FASEB J. 2001 Jul;15(9):1622-4

# Tegeder I, Niederberger E, Schmidt R, Kunz S, Gühring H, Ritzeler O, Michaelis M, Geisslinger G. Specific inhibition of I-kappaB kinase (IKK) reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J Neurosci 2004;24(7):1637-45

# Klinkhardt U, Adams J, Graff J, Bauersachs R, Lindhoff-Last E, Harder S.
Clopidogrel, but not Aspirin reduces formation of platelet-leukocyte conjugates and P-selectin ex-pression in patients with peripheral vascular disease. Clin Pharmacol Ther. 2003 Mar;73(3):232-41

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