Understanding the mechanisms that generate pain remains one of the essential goals for developing more effective treatments targeting chronic pain pathways. Over recent years it has become evident that lipids like prostaglandins or diacylglycerol modulate pain perception. There are several unresolved issues. For many of these novel lipid mediators, it is not known whether they are produced during tissue injury or inflammation, if so, which cells contribute to their production, and whether they have direct actions on sensory neurons, or on neurons in the dorsal horn of the spinal cord. Sphingolipids have long been recognised as a component of cell membranes but it is now known that the sphingolipid - sphingosine 1-phosphate (S1P) - has a multitude of functions in the regulation and maintenance of the body’s organ systems.
Nerve injury or inflammation of peripheral nerves induces changes in the mRNA profile of thousands of genes. This must be coordinated in some way. We think that differences in the control of protein synthesis by microRNAs not only underlie the differences in pain susceptibility between individuals but also the development of chronic pain in a subset of patients. To do so, we compare the expression of microRNAs in nociceptive neurons from strains of animals that differ significantly in their response to noxious stimuli in response to nerve injury. We then investigate which mRNAs, proteins and signalling pathways are targeted by miRNAs and how they can be modulated through changes in miRNA expression.
Adequate lung function is essential for terrestrial animals, including humans. Breathing problems are especially critical for young children and the elderly. Neural monitoring of the internal environment of the lung is essential for airway function and survival of terrestrial animals. With the increase of inflammatory airway diseases, such as asthma and COPD, new knowledge about the regulation of lung function is critical for developing new therapies that will enhance or replace existing treatments. Sphingolipid 1-phosphate and stimulation of its receptors affect tissues and cells within the lung in many ways. The function and localisation within individual cells in human lung are unknown.
Dr Michael Michael (Gastroenterology, Flinders University) and Prof Xin-Fu Zhou (Human Physiology, Flinders University): miRNAs in nociceptive neurons.
Prof Ian Gibbins, Anatomy & Histology, Flinders University: Investigation of sphingolipids as modulators of synaptic transmission in the dorsal horn.
Prof Michaela Kress, Department of Physiology, University of Innsbruck, Austria: Investigation of sphingolipids as modulators of synaptic transmission in the dorsal horn.
Dr Robyn Meech, Clinical Pharmacology, Flinders University: Epigenetic mechanisms in the control of nociceptor function.
Dr Ernest Jennings, School of Medicine & Dentistry, James Cook University, Cairns: miRNAs and nociceptor function.
Dr Brett Graham, School of Biomedical Sciences and Pharmacy, University Newcastle: Epigenetic mechanisms in the control of nociceptor function.
Dr Martin Witzenrath and Dr Christoph Tabeling, Department of Infectious Diseases and Respiratory Medicine, Charite, Universitätsmedizin Berlin, Germany: S1P in the lung.
Assoc Prof Sandy Hodge, Assoc Prof Hubertus Jersmann, University of Adelaide, Hanson Institute: S1P signalling in peripheral human airways.
Prof Malcolm Smith, Repatriation General Hospital, Adelaide: Investigation of dendritic cells in the human synovia.
Prof Andreas Meinhardt, Institute for Anatomy and Cell Biology, Justus-Liebig-University Giessen: Investigation of the cholinergic system and sensory innervation of the male reproductive system.
Dr Stuart Pitson, Institute for Medical and Veterinary Science (IMVS), Hanson Institute: Investigation of sphingosine kinase 1-deficient mice.
Vilimas PI, Yuan SY, Haberberger RV, Gibbins IL (In press) Sensory Innervation of the External Genital Tract of Female Guinea Pigs and Mice. J Sex Med [Epub ahead of print]
Schirmer S, Eckhardt I, Klein J, Lau H, DeGraaf Y, Lips KS, Pineau C, Gibbins IL, Kummer W, Meinhardt A, Haberberger RV (In press) The cholinergic system in rat testis is of non-neuronal origin. Reproduction [Epub ahead of print]
Bastian I, Tam Tam S, Zhou XF, Kazenwadel J, Van der Hoek M,
Michael MZ, Gibbins I, Haberberger RV (2011) Differential expression
of microRNA-1 in dorsal root ganglion neurons. Histochem
Cell Biol. 135(1):37-45
Mair N, Benetti C, Andratsch M, Leitner MG, Constantin CE, Camprubí-Robles M, Quarta S, Biasio W, Kuner R, Gibbins IL, Kress M, Haberberger RV (2011) Genetic evidence for involvement of neuronally expressed S1P1 receptor in nociceptor sensitization and inflammatory pain. PLoS One, 6(2):e1726
Wilson AJ, Carati CJ, Gannon BJ, Haberberger R, Chataway TK (2010)
Aquaporin-1 in blood vessels of rat circumventricular organs. Cell
Tissue Res. 340(1):159-68
Klein MK, Haberberger RV, Hartmann P, Faulhammer P, Lips KS,
Krain B, Wess J, Kummer W, Konig P (2009) Muscarinic
receptor subtypes in cilia-driven transport and airway epithelial
development. Eur Respir J, 33(5):1113-1121
Haberberger RV, Tabeling C, Runciman S, Gutbier B, Konig P, Andratsch
M, Schutte H, Suttorp N, Gibbins I, Witzenrath M (2009)
Role of sphingosine kinase 1 in allergen-induced pulmonary vascular
remodeling and hyperresponsiveness. J Allergy Clin Immunol,
124(5):933-941 e931-939
Jositsch G, Papadakis T, Haberberger RV, Wolff M, Wess J, Kummer
W (2009) Suitability of muscarinic acetylcholine
receptor antibodies for immunohistochemistry evaluated on tissue
sections of receptor gene-deficient mice. Naunyn Schmiedebergs
Arch Pharmacol, 379(4):389-395
Kindt F, Wiegand S, Niemeier V, Kupfer J, Löser C, Nilles
M, Kurzen H, Kummer W, Gieler U, Haberberger RV (2008) Reduced
expression of nicotinic alpha 3, 7, 9 and 10 subunits in lesional
and non-lesional atopic dermatitis skin but enhanced expression
of alpha 3 and 5 subunits in mast cells. Br J Dermatol, 159(4):847-57
Ahlbrecht K, Schmitz J, Schwarz C, Seay U, Mitnacht-Kraus R,
Gaumann A, Haberberger RV, Herold S, Breier G, Grimminger F, Seeger
W, Voswinckel R (2008) Spatiotemporal
expression of flk-1 in pulmonary epithelial cells during lung development. Am
J Respir Cell Mol Biol, 39:163-70
Kress M, Karasek J, Ferrer-Montiel A, Scherbakov N, Haberberger
RV (2008) TRPC channels and diacylglycerol dependent calcium signaling
in rat sensory neurons. Histochem
Cell Biol, 130(4):655-67
Lips KS, Luhrmann A, Tschernig T, Stoeger T, Alessandrini F,
Grau V, Haberberger RV, Koepsell H, Pabst R, Kummer W (2007)
Down-regulation of the non-neuronal acetylcholine synthesis and
release machinery in acute allergic airway inflammation of rat
and mouse. Life Sci. 80(24-25):2263-9
Kindt F, Wiegand S, Loser C, Nilles M, Niemeier V, Hsu SY, Steinhoff
M, Kummer W, Gieler U, Haberberger RV (2007)
Intermedin: a skin peptide that is downregulated in atopic dermatitis. J
Invest Dermatol. 127(3):605-13
