Pathology and glia type specific changes of the DPP4 activity in the spinal cord contributes to the development and maintenance of hyperalgesia and shapes opioid signalling in chronic pain states

Király, Kornél and Kozsurek, Márk and Lukácsi, Erika and Barta, Benjamin and Alpár, Alán and Balázsa, Tamás and Fekete, Csaba and Szabon, Judit and Helyes, Zsuzsanna and Bölcskei, Kata and Tekus, Valeria and Tóth, Zsuzsanna and Pap, Károly and Gerber, Gábor and Puskár, Zita (2017) Pathology and glia type specific changes of the DPP4 activity in the spinal cord contributes to the development and maintenance of hyperalgesia and shapes opioid signalling in chronic pain states. SCIENTIFIC REPORTS. ISSN 2045-2322 (Submitted)

Preview

Text DPP4_Scientific Reports_MS 2017 09 04.pdf Download (385kB) | Preview

Abstract

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various chronic pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) enzyme inhibitors results in a strong antihyperalgesic effect during inflammatory pain states. In this study we observed a low level of mRNA for DPP4 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. Although DPP4 protein was detected in neurons, astrocytes and microglia in naïve animals its expression significantly increased in astrocytes during inflammation and in microglia in neuropathic conditions. Intrathecal application of two DPP4 inhibitors the tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation and an opioid-independent effect in the Seltzer 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. Our results suggest a pathology and glia type specific changes of the DPP4 activity in the spinal cord which contributes to the development and maintenance of hyperalgesia and shapes opioid signalling.

Actions (login required)

Edit Item