Fried Laboratory


Kaj Fried

Phone: 08-524 878 53
Organizational unit: Department of Neuroscience (Neuro), C4

Research focus

Craniofacial neuropathic pain

Chronic pain in the craniofacial region (“trigeminal chronic pain”) is a common medical problem that is difficult to treat; currently available remedies are compromised by side effects and offer only partial pain relief. Like other chronic pain syndromes, trigeminal pain is a complex genetic trait; analyses of human and animal models indicate that ~50% of the inter-individual differences in neuropathic pain levels are genetically controlled.

Our objective is to identify genetic factors affecting trigeminal pain syndromes, with emphasis on orofacial conditions. This may open new ways of understanding the functional relationship between nociceptors and their surrounding tissue, and be helpful in search for better therapies against dental pain.

The role of the peripheral innervation in the formation of teeth
From an evolutionary standpoint, teeth are essential for both feeding and fending. Teeth develop through very complex mechanisms through coordinated actions between neural crest stem cells and the ectoderm of a brachial arch. They consist of a hard matrix and matrix producing cells (odontoblasts), pulp cells, vessels and a protective sensory innervation with adjacent glia. Available evidence has suggested that the developmental growth and establishment of sensory pain-transmitting nerve terminals in relation to teeth are controlled by local molecular signals. We address the role of a sensory nerve as a provider of tooth stem cells during the development, adulthood and in regeneration. We use genetic tracing with multicolor reporters, transgenic mice with cell type-specific modifications in signaling, microsurgery and grafting, in vitro cell cultures and 3D-imaging.

Schwann cell precursors from nerve give rise to dental mesenchymal stem cells in the adult incisor tooth. Adult traced adult PLP-CreERT2/R26Confetti incisor with streams of YFP+ and RFP+ pulp cells spatially connected to YFP+ and RFP+ clusters of odontoblasts (upper left, frame magnified in upper right). Below left: Streams of pulp cells (arrows) initiated in proximity to the cervical loop. Yellow and red isosurfaces generated around YFP+ and RFP+ cells. The progenies of individual mesenchymal stems cells intermingle with neighboring clones in the pulp (below, middle) and in odontoblast layer (below, right). (From Kaukua et al, 2014)

Selected publications

The paradox of pain from tooth pulp: low-threshold "algoneurons"?
Fried K, Sessle B, Devor M
Pain 2011 Dec;152(12):2685-9

Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.
Dyachuk V, Furlan A, Shahidi M, Giovenco M, Kaukua N, Konstantinidou C, et al
Science 2014 Jul;345(6192):82-7

Glial origin of mesenchymal stem cells in a tooth model system.
Kaukua N, Shahidi M, Konstantinidou C, Dyachuk V, Kaucka M, Furlan A, et al
Nature 2014 Sep;513(7519):551-4

Molecular differences between stromal cell populations from deciduous and permanent human teeth.
Kaukua N, Chen M, Guarnieri P, Dahl M, Lim M, Yucel-Lindberg T, et al
Stem Cell Res Ther 2015 Apr;6():59

Three-dimensional Imaging Reveals New Compartments and Structural Adaptations in Odontoblasts.
Khatibi Shahidi M, Krivanek J, Kaukua N, Ernfors P, Hladik L, Kostal V, et al
J. Dent. Res. 2015 Jul;94(7):945-54

Group members

Vyatcheslav Dyachuk - Postdoc

Anna Nele Herdina - Postdoc

Nina Kaukua - PhD

Dmitrii Kamenev - Postdoc