Cellular and Molecular Research Group

Main Topics of the Research Group

A. Beneficial and detrimental neuro-immune interactions during induction and maintenance of neuropathic pain.

B. Propagation of neuroinflammatory reaction in the nervous system after peripheral nerve injury in various neuropathic pain models and its control.

C. Signaling from Wallerian degeneration to neuroinflammatory reaction in remote structures and its possible control.

D. Neuroinflammatory reactions of peripheral and central glial cells, their involvement and control in neuropathic pain induction after experimental nerve injury.

E. Balance between nerve regeneration and neuropathic pain induction.

F. Barriers of the nervous system and their breaks after neuroinflammation and diseases.

G. Endocannabinoid system and the control of neuropathic pain induction.

H. Interactions between opioid and chemokine receptors.

Particular Questions

Cytokines/chemokines and their receptors of activated Schwann cells distal to nerve lesion, their involvement in neuropathic pain induction as well as promotion of axon regeneration.

Up-regulation of cytokines/chemokines and their receptors by activated satellite glial cells and their contribution to misbalances of spinal or trigeminal afferentation.

A role of cytokines/chemokines and their receptors in functional competence of opioid receptors in nociceptors.

Wallerian degeneration as aseptic inflammation and source of mitochondrial damage-associated molecular patterns (mtDAMPs) for local activation of Schwann cells and spread neuroinflammatory reaction in remote CNS structures.

Investigation of cytokine/chemokine expression in neurons, microglial cells and astrocytes in supraspinal structures in the experimental models of neuropathic pain.

The study of nervous system barriers interrupted during serious disease and injuries (e.g., after subarachnoid hemorrhage, traumatic nerve or spinal cord injuries).

Correlation and comparison of experimental neuropathic pain models with human diseases associated with neuropathic pain (e.g., cancer chemotherapy-induced pain).

Up-regulation of cannabinoid receptors (CB1, CB2) in the nervous structures as expression of endocannabinoid system activity, their links with neuroinflammatory reactions and possible modulation.

Models and Methods

- Rat and mouse experimental models of neuropathic pain based on traumatic nerve injury or cancer chemotherapy; experimental model of subarachnoid hemorrhage

- Behavioral tests of mechano- and thermal hypersensitivity

- Electrophysiology of ex vivo model of skin-nerve preparation

- In vitro cultivation and assessment of neuronal and glial cells

- Light and electron microscopy; mapping of neuronal connections by tracers; immuno-histochemical detection (in situ proteomics), tissue arrays

- Molecular biology methods (ELISA, Western blot; in situ hybridization, RT-PCR)

Selected Publications

Joukal M, Vulchanova L, Huffman C, Dubový P, Honda CN (2020) Peripheral deltorphin II inhibits nociceptors following nerve injury. Front Pharmacol. 11:1151 https://doi.org/10.3389/fphar.2020.01151
Kubíčková L, Klusáková I, Dubový P (2020) Bilateral activation of glial cells and cellular distribution of the chemokine CCL2 and its receptor CCR2 in the trigeminal subnucleus caudalis of trigeminal neuropathic pain model. Histochemistry and Cell Biology, https://doi.org/10.1007/s00418-020-01850-4
Solár P, Klusáková I, Jančálek R, Dubový P, Joukal M (2020) Subarachnoid Hemorrhage Induces Dynamic Immune Cell Reactions in the Choroid Plexus. Front Cell Neurosci 14, 18. https://doi.org/10.3389/fncel.2020.00018
Dubový P, Hradilová-Svíženská I, Klusáková I, Brázda V, Joukal M (2019) Interleukin-6 contributes to initiation of neuronal regeneration program in the remote dorsal root ganglia neurons after sciatic nerve injury. Histochem Cell Biol 152:109–117. https://doi.org/10.1007/s00418-019-01779-3
Dubový P, Klusáková I, Hradilová-Svíženská I, Brázda V, Kohoutková M, Joukal M (2019) A Conditioning Sciatic Nerve Lesion Triggers a Pro-regenerative State in Primary Sensory Neurons Also of Dorsal Root Ganglia Non-associated With the Damaged Nerve. Front Cell Neurosci 13:11. https://doi.org/10.3389/fncel.2019.00011
Korimová A, Klusáková I, Hradilová-Svíženská I, Kohoutková M, Joukal M, Dubový P (2018) Mitochondrial Damage-Associated Molecular Patterns of Injured Axons Induce Outgrowth of Schwann Cell Processes. Front Cell Neurosci 12, 457. https://doi.org/10.3389/fncel.2018.00457
Dubový P, Klusáková I, Hradilová Svíženská I, Joukal M, Boadas-Vaello P (2018) Activation of Astrocytes and Microglial Cells and CCL2/CCR2 Upregulation in the Dorsolateral and Ventrolateral Nuclei of Periaqueductal Gray and Rostral Ventromedial Medulla Following Different Types of Sciatic Nerve Injury. Front Cell Neurosci 12:40. https://doi.org/10.3389/fncel.2018.00040
Dubový P, Hradilová-Svíženská I, Klusáková I, Kokošová V, Brázda V, Joukal M (2018) Bilateral activation of STAT3 by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and its nuclear translocation in primary sensory neurons following unilateral sciatic nerve injury. Histochem Cell Biol 150:37–47. https://doi.org/10.1007/s00418-018-1656-y
Kohoutková M, Korimová A, Brázda V, Kohoutek J, Dubový P (2017) Early inflammatory profiling of schwannoma cells induced by lipopolysaccharide. Histochem Cell Biol 148:607–615. https://doi.org/10.1007/s00418-017-1601-5
Hernangomez M, Klusáková I, Joukal M, Hradilová-Svíženská I, Guaza C, Dubový P (2016) CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model. J Neuroinflammation 13:43. https://doi.org/10.1186/s12974-016-0508-8
Joukal M, Klusáková I, Dubový P (2016a) Direct communication of the spinal subarachnoid space with the rat dorsal root ganglia. Ann Anat-Anat Anz 205:9–15. https://doi.org/10.1016/j.aanat.2016.01.004
Joukal M, Klusáková I, Solár P, Kuklová A, Dubový P (2016b) Cellular reactions of the choroid plexus induced by peripheral nerve injury. Neurosci Lett 628:73–77. https://doi.org/10.1016/j.neulet.2016.06.019
Dubový P, Klusáková I, Hradilová Svíženská I (2014) Inflammatory Profiling of Schwann Cells in Contact with Growing Axons Distal to Nerve Injury. BioMed Res Int 2014: 1–7. https://doi.org/10.1155/2014/691041
Dubový P, Brázda V, Klusáková I, Hradilová-Svíženská I (2013) Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve. J Neuroinflammation 10:824. https://doi.org/10.1186/1742-2094-10-55
Dubový P (2011) Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Ann Anat-Anat Anz 193:267–275. https://doi.org/10.1016/j.aanat.2011.02.011

Main Partners and Collaborating Institutions

Dr. Lucy Vulchanova, Department of Neuroscience, University of Minnesota, USA

Prof. Stefano Geuna, Department of Clinical and Biological Sciences, University of Torino, Italy

Prof. Lars Klimaschewski, Division of Neuroanatomy, University of Innsbruck, Austria

Dr. Xavier Navarro, Grup de Neuroplasticitat i Regeneracio, Dept. Biologia Cel.lular, Fisiologia i Immunologia, Institut de Neurociencies, Universitat Autonoma de Barcelona, Spain

Dr. Pere Boadas-Vaello, Departament de Ciències Mèdiques. Àrea Fisiologia Facultat de Medicina. Universitat de Girona, Spain