Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain
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 inflammato...
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2018
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oai:doaj.org-article:24d74c8afb4446d58b71a3a0eb302c9f2021-12-02T11:41:02ZGlial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain10.1038/s41598-018-21799-82045-2322https://doaj.org/article/24d74c8afb4446d58b71a3a0eb302c9f2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21799-8https://doaj.org/toc/2045-2322Abstract 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.Kornél KirályMárk KozsurekErika LukácsiBenjamin BartaAlán AlpárTamás BalázsaCsaba FeketeJudit SzabonZsuzsanna HelyesKata BölcskeiValéria TékusZsuzsanna E. TóthKároly PapGábor GerberZita PuskárNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
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Medicine R Science Q Kornél Király Márk Kozsurek Erika Lukácsi Benjamin Barta Alán Alpár Tamás Balázsa Csaba Fekete Judit Szabon Zsuzsanna Helyes Kata Bölcskei Valéria Tékus Zsuzsanna E. Tóth Károly Pap Gábor Gerber Zita Puskár Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| description |
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. |
| format |
article |
| author |
Kornél Király Márk Kozsurek Erika Lukácsi Benjamin Barta Alán Alpár Tamás Balázsa Csaba Fekete Judit Szabon Zsuzsanna Helyes Kata Bölcskei Valéria Tékus Zsuzsanna E. Tóth Károly Pap Gábor Gerber Zita Puskár |
| author_facet |
Kornél Király Márk Kozsurek Erika Lukácsi Benjamin Barta Alán Alpár Tamás Balázsa Csaba Fekete Judit Szabon Zsuzsanna Helyes Kata Bölcskei Valéria Tékus Zsuzsanna E. Tóth Károly Pap Gábor Gerber Zita Puskár |
| author_sort |
Kornél Király |
| title |
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| title_short |
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| title_full |
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| title_fullStr |
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| title_full_unstemmed |
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| title_sort |
glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/24d74c8afb4446d58b71a3a0eb302c9f |
| work_keys_str_mv |
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1718395449768935424 |