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INSTITUTE OF PHYSIOLOGY CAS

Cutting-edge science for health

Laboratory of Pain Research

Laboratory of Pain Research Recording of electrophysiological activity from dorsal horn neurons in acute spinal cord slices with patch-clamp technique.

The main research interest of our Laboratory is to study mechanisms of pain and to explore new possibilities of pain treatment, especially in chronic states. Our experimental work is concentrated on the modulation of nociceptive information at the spinal cord level that is the relay center between the periphery and the higher brain areas. Our goal is to study these modulatory mechanisms in order to improve therapy for pain conditions, such as allodynia, hyperalgesia, neuropathic and cancer related pain. Our focus is on the role of TRPV1, purinergic P2X receptors and inflammatory cytokines. In our research we use mainly electrophysiological, optogenetic,  immunohistochemical and behavioral methods.

The group of Cellular and Molecular Neuroendocrinology headed by Dr. Zemková also investigates the relationship between structure and function of  P2X receptor-channels and their involved in electrical activity, calcium signaling, and release of hormones and neurotransmitters  in neuroendocrine cells.

 

Projects

Chemotherapy induced neuropathic pain

Scientists from the Department of Functional Morphology in collaboration with colleagues from The University of Texas showed that paclitaxel induced pain is mediated by TRPV1 and TLR4 receptors. More

Inhibition effect of NAPE at spinal cord level

N-acylphosphatidylethanolamine (NAPE), as the precursor of anandamide, an endogenous agonist of TRPV1 and cannabinoid receptors, could play a role in modulation of nociceptive signalization in the spinal cord. More

The role of spinal TRPV1 receptors in CCL2-induced hyperalgesia

Modulation of nociceptive synaptic transmission in the spinal cord is implicated in the development and maintenance of several pathological pain states. The chemokine CCL2 (C-C motif ligand 2) was shown to be an important factor in the development of neuropathic pain after peripheral nerve injury, when it may be released from the central endings of primary nociceptive neurons in the spinal cord dorsal horn. More

The role of PAR2 receptors in modulation of nociceptive signalling at the spinal cord level

Modulation of synaptic transmission in the spinal cord dorsal horn plays a key role in the development of pathological pain states. Protease-activated receptors (PARs) belong to a family of four G-protein-coupled receptors (PAR1-4) activated by proteases. Proteases and PARs occur in many tissues like intestine, lungs, kidneys, endothelium, and mast cell and in the central and peripheral nervous systems. Proteases and PARs are involved in neuronal and astrocyte survival, proliferation and morphology, release of neurotransmitters, and also modulate the function and activity of ion channels. More

Achievements

Our new paper: Ivermectin action on ligand-gated ion channels

Ivermectin is a large lipophilic molecule that acts as a positive allosteric regulator of several ligand-gated channels including the glutamate-gated chloride channel, gamma aminobutyric acid type-A receptor, glycine receptor, neuronal alpha7-nicotinic receptor and purinergic P2X4 receptor. This review summarizes what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structural determinants underlying potentiation of the P2X4 receptor channel. More

Our new paper: Allosteric modulation of P2X4 receptor channel conductivity.

Allosteric modulators of ligand-gated receptor channels induce conformational changes of the entire protein that alter potencies and efficacies for orthosteric ligands, expressed as the half maximal effective concentration  and maximum current amplitude, respectively. The influence of allostery on channel pore size, an issue not previously addressed, was studied. More

Our new paper: CRH-induced excitability in pituitary corticotrophs

Corticotorpin releasing hormone (CRH), a key regulator of HPA axis, is secreted by hypothalamic paraventricular neurons into the hypophysial portal system and stimulates ACTH secretion in pituitary corticotorphs. The data show that resting membrane potential in corticotrophs depends on background voltage-insensitive sodium conductance, and that CRH has biphasic actions: a depolarizing effect driven by a cationic conductance at basal concentrations in pituitary portal circulation and an inhibitory effect at higher stress CRH concentrations More

Publications

Kalynovska; Nataliia - Diallo; Mickael - Sotáková-Kašparová; Dita - Paleček; Jiří . Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy . Journal of Cellular and Molecular Medicine. 2020; 24(14); 7949-7958 . IF = 4.486 [ASEP] [ doi ]
Sýkora; M. - Szeiffová Bačová; B. - Egan Beňová; T. - Barančík; M. - Žurmanová; J. - Rauchová; Hana - Weismann; P. - Pavelka; Stanislav - Kurahara; L. H. - Slezák; J. - Soukup; Tomáš - Tribulová; N. Cardiac Cx43 and ECM Responses to Altered Thyroid Status Are Blunted in Spontaneously Hypertensive versus Normotensive Rats . International Journal of Molecular Sciences. 2019; 20(15)); 3758 . IF = 4.556 [ASEP] [ doi ]
Kalynovska, Nataliia - Diallo, Michael - Paleček, Jiří . Losartan treatment attenuates the development of neuropathic thermal hyperalgesia induced by peripheral nerve injury in rats . Life Sciences 2019, 220(Mar 1), 147-155 . IF = 3.647 [ASEP] [ doi ]
Adámek, Pavel - Heleš, Mário - Paleček, Jiří . Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy . Neuropharmacology 2019, 146(Mar 1), 163-174 . IF = 4.431 [ASEP] [ doi ]
Torres-Pérez, J. V. - Adámek, Pavel - Paleček, Jiří - Vizcaychipi, M. - Nagy, I. - Varga, A. The NA(v)1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing . Journal of Molecular Medicine-Jmm 2018, roč. 96, 1, p. 75-84 . IF = 4.746 [ASEP] [ doi ]

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People

Jiří Paleček, MD, PhD
Head of the Laboratory
Mgr. Diana Špicarová, Ph.D.
Deputy Head of the Laboratory
RNDr. Hana Zemková, CSc.
Senior Researcher
Anirban Bhattacharya, Ph.D.
Senior Researcher
Ing. Irena Svobodová, Ph.D. 
Senior Researcher
Mgr. Petra Mrózková, Ph.D.
Postdoctoral Fellow
RNDr. Pavel Adámek, Ph.D.
Postdoctoral Fellow
Mgr. Mario Heleš
PhD Student
Mgr. Jakub Slepička
PhD Student
Mgr. Monica Pontearso
PhD Student
  Mgr. Marian Rupert
PhD Student
  Mgr. Sonja Sivcev
PhD Student
 

Mgr. Jana Cimická

PhD Student

 

David Mužík

Student

 

Anna Kratinová

Student

 

Tereza Pribáňová

Student

Ing. Hana Janoušková
Technician
Kateřina Kramerová
Technician