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

Kornél Király, Márk Kozsurek, Erika Lukácsi, Benjamin Barta, A. Alpár, Tamás Balázsa, Csaba Fekete, Judit Szabon, Z. Helyes, K. Bölcskei, Valéria Tékus, Z. Tóth, Károly Pap, Gábor Gerber, Z. Puskár

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number3490
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Dipeptidyl Peptidase 4
Hyperalgesia
Neuroglia
Opioid Analgesics
Dipeptidyl-Peptidase IV Inhibitors
Pain
mu Opioid Receptor
Microglia
Astrocytes
Inflammation
kappa Opioid Receptor
delta Opioid Receptor
Carrageenan
Hypoglycemic Agents
Ligation
Spinal Cord
Maintenance
Pathology
Neurons
Messenger RNA

ASJC Scopus subject areas

  • General

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Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain. / Király, Kornél; Kozsurek, Márk; Lukácsi, Erika; Barta, Benjamin; Alpár, A.; Balázsa, Tamás; Fekete, Csaba; Szabon, Judit; Helyes, Z.; Bölcskei, K.; Tékus, Valéria; Tóth, Z.; Pap, Károly; Gerber, Gábor; Puskár, Z.

In: Scientific Reports, Vol. 8, No. 1, 3490, 01.12.2018.

Research output: Contribution to journalArticle

Király, Kornél ; Kozsurek, Márk ; Lukácsi, Erika ; Barta, Benjamin ; Alpár, A. ; Balázsa, Tamás ; Fekete, Csaba ; Szabon, Judit ; Helyes, Z. ; Bölcskei, K. ; Tékus, Valéria ; Tóth, Z. ; Pap, Károly ; Gerber, Gábor ; Puskár, Z. / Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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AU - Alpár, A.

AU - Balázsa, Tamás

AU - Fekete, Csaba

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AU - Helyes, Z.

AU - Bölcskei, K.

AU - Tékus, Valéria

AU - Tóth, Z.

AU - Pap, Károly

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