Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain.

Autor:	Király K; Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089, Budapest, Hungary., Kozsurek M; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Lukácsi E; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Barta B; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Alpár A; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Balázsa T; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Fekete C; 'Lendület' Laboratory of Integrative Neurobiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, H-1083, Budapest, Hungary., Szabon J; 'Lendület' Laboratory of Integrative Neurobiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, H-1083, Budapest, Hungary., Helyes Z; Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, H-7624, Pécs, Hungary.; MTA-PTE NAP B Chronic Pain Research Group, University of Pécs, H-7624, Pécs, Hungary., Bölcskei K; Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, H-7624, Pécs, Hungary., Tékus V; Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, H-7624, Pécs, Hungary., Tóth ZE; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Pap K; Department of Traumatology, Semmelweis University, H-1113 Budapest, Hungary & Department of Orthopaedics and Traumatology, Uzsoki Hospital, H-1145, Budapest, Hungary., Gerber G; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary., Puskár Z; Department of Anatomy, Histology and Embryology, Semmelweis University, H-1094, Budapest, Hungary. puskar.zita@med.semmelweis-univ.hu.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 Feb 22; Vol. 8 (1), pp. 3490. Date of Electronic Publication: 2018 Feb 22.
DOI:	10.1038/s41598-018-21799-8
Abstrakt:	Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.
Databáze:	MEDLINE
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