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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.

An important role play PARs in the response to tissue injury, especially in the process of inflammation and repair. Out of the four PARs subtypes, most of the published studies concentrated on the role and function of the PAR2 subtype. PAR2 receptors are expressed in the brain, spinal cord and dorsal root ganglia (DRG) neurons. The role of PAR2 receptors in pain perception is closely related to their presence in a population of DRG neurons, where they are also co-expressed with transient potential receptor vanilloid 1 (TRPV1). TRPV1 receptor is a non-selective cationt channel expressed by nociceptive neurons that mediates inflammatory and thermal hyperalgesia.

Activation of PAR2 receptor in the peripheral nerve endings may lead to TRPV1 increased sensitivity during inflammation. The role of PAR2 receptors on the presynaptic endings of primary afferents in the spinal cord dorsal horn is not fully understood. We focus on the role of PAR2 receptors in nociceptive processing and in modulation of synaptic transmission and the possible interaction with TRPV1 receptors at the spinal cord level.  In our experiments PAR2 receptors are activated by application of SLIGKV-NH2, inactive peptide VKGILS-NH2 is used as a control.

Mrózková, Petra - Špicarová, Diana - Paleček, Jiří . Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors . PLoS ONE. 2016, roč. 11, 10, článku e0163991 . IF = 2.806