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001-es BibID:BIBFORM109585
035-os BibID:(cikkazonosító)1115685 (Scopus)85150718609 (WoS)000951373400001
Első szerző:Ducza László (molekuláris biológus)
Cím:Neuronal P2X4 receptor may contribute to peripheral inflammatory pain in rat spinal dorsal horn / Ducza László, Gajtkó Andrea, Hegedűs Krisztina, Bakk Erzsébet, Kis Gréta, Gaál Botond, Takács Roland, Szücs Péter, Matesz Klára, Holló Krisztina
Megjegyzések:Objective: Intense inflammation may result in pain, which manifests as spinal central sensitization. There is growing evidence that purinergic signaling plays a pivotal role in the orchestration of pain processing. Over the last decade the ionotropic P2X purino receptor 4 (P2X4) got into spotlight in neuropathic disorders, however its precise spinal expression was scantily characterized during inflammatory pain. Thus, we intended to analyze the receptor distribution within spinal dorsal horn and lumbar dorsal root ganglia (DRG) of rats suffering in inflammatory pain induced by complete Freund adjuvant (CFA). Methods: CFA-induced peripheral inflammation was validated by mechanical and thermal behavioral tests. In order to ensure about the putative alteration of spinal P2X4 receptor gene expression qPCR reactions were designed, followed by immunoperoxidase and Western blot experiments to assess changes at a protein level. Colocalization of P2X4 with neuronal and glial markers was investigated by double immunofluorescent labelings, which were subsequently analyzed with IMARIS software. Transmission electronmicroscopy was applied to study the ultrastructural localization of the receptor. Concurrently, in lumbar DRG cells similar methodology has been carried out to complete our observations. Results: The figures of mechanical and thermal behavioral tests proved the establishment of CFA-induced inflammatory pain. We observed significant enhancement of P2X4 transcript level within the spinal dorsal horn 3?days upon CFA administration. Elevation of P2X4 immunoreactivity within Rexed lamina I-II of the spinal gray matter was synchronous with mRNA expression, and confirmed by protein blotting. According to IMARIS analysis the robust protein increase was mainly detected on primary afferent axonterminals and GFAP-labelled astrocyte membrane compartments, but not on postsynaptic dendrites was also validated ultrastructurally within the spinal dorsal horn. Furthermore, lumbar DRG analysis demonstrated that peptidergic and non-peptidergic nociceptive subsets of ganglia cells were also abundantly positive for P2X4 receptor in CFA model. Conclusion: Here we provide novel evidence about involvement of neuronal and glial P2X4 receptor in the establishment of inflammatory pain.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
inflammatory pain
spinal dorsal horn
P2X4 receptor
central sensitization
primary afferents
glial cells
dorsal root ganglia
Megjelenés:Frontiers in Molecular Neuroscience. - 16 (2023), p. 1-16. -
További szerzők:Gajtkó Andrea (1989-) (molekuláris biológus) Hegedűs Krisztina Bakk Erzsébet Kis Gréta (1979-) (molekuláris biológus) Gaál Botond Ágoston (1982-) (anatómus, neurobiológus) Takács Roland Ádám (1985-) (molekuláris biológus, biokémikus) Szűcs Péter (1974-) (kutatóorvos) Matesz Klára (1949-) (anatómus, neurobiológus) Holló Krisztina (1967-) (vegyész)
Pályázati támogatás:KTIA_NAP_13-2-2014-0005
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