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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Authors: Krisztina Holló, László Ducza, Zoltán Hegyi, Klaudia Dócs, Krisztina Hegedűs, Erzsébet Bakk, Ildikó Papp, Gréta Kis, Zoltán Mészár, Zsuzsanna Bardóczi, Miklós Antal

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

All known biological functions of the pro-inflammatory cytokine interleukin-1β (IL-1β) are mediated by type 1 interleukin receptor (IL-1R1). IL-1β–IL-1R1 signaling modulates various neuronal functions including spinal pain processing. Although the role of IL-1β in pain processing is generally accepted, there is a discussion in the literature whether IL-1β exerts its effect on spinal pain processing by activating neuronal or glial IL-1R1. To contribute to this debate, here we investigated the expression and cellular distribution of IL-1R1 in the superficial spinal dorsal horn in control animals and also in inflammatory pain.

Methods

Experiments were performed on rats and wild type as well as IL-1R1-deficient mice. Inflammatory pain was evoked by unilateral intraplantar injection of complete Freund adjuvant (CFA). The nociceptive responsiveness of control and CFA-treated animals were tested daily for withdrawal responses to mechanical and thermal stimuli before and after CFA injection. Changes in the expression of 48 selected genes/mRNAs and in the quantity of IL-1R1 protein during the first 3 days after CFA injection were measured with the TaqMan low-density array method and Western blot analysis, respectively. The cellular localization of IL-1R1 protein was investigated with single and double staining immunocytochemical methods.

Results

We found a six times and two times increase in IL-1R1 mRNA and protein levels, respectively, in the dorsal horn of CFA-injected animals 3 days after CFA injection, at the time of the summit of mechanical and thermal allodynia. Studying the cellular distribution of IL-1R1, we found an abundant expression of IL-1R1 on the somatodendritic compartment of neurons and an enrichment of the receptor in the postsynaptic membranes of some excitatory synapses. In contrast to the robust neuronal localization, we observed only a moderate expression of IL-1R1 on astrocytes and a negligible one on microglial cells. CFA injection into the hind paw caused a remarkable increase in the expression of IL-1R1 in neurons, but did not alter the glial expression of the receptor.

Conclusion

The results suggest that IL-1β exerts its effect on spinal pain processing primarily through neuronal IL-1R1, but it can also interact in some extent with IL-1R1 expressed by astrocytes.
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Metadata
Title
Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain
Authors
Krisztina Holló
László Ducza
Zoltán Hegyi
Klaudia Dócs
Krisztina Hegedűs
Erzsébet Bakk
Ildikó Papp
Gréta Kis
Zoltán Mészár
Zsuzsanna Bardóczi
Miklós Antal
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0902-x

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