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Open Access 14-05-2024 | Glucocorticoid | Original Article

Corticotropin-releasing hormone deficiency results in impaired analgesic response during CFA-induced inflammation

Authors: Efthymia Karagianni, Olga Rassouli, Smaragda Poulaki, Eirini Dermitzaki, George Liapakis, Andrew N. Margioris, Maria Venihaki

Published in: Hormones

Abstract

Purpose

Corticotropin-releasing hormone (CRH) plays an important role in relief of pain by releasing analgesia-associated molecules in several inflammatory states. During inflammation, peripheral CRH acts on cells of the immune system to stimulate the local expression of proopiomelanocortin (POMC) and the production of β-endorphin, which in turn binds to opioid receptors on sensory neurons to produce antinociception. In the present study, we further investigated the role of endogenous CRH in inflammatory pain by determining the effects of Crh-deficiency on this process.

Methods

For this purpose, we used Crh-deficient (Crh-/-) mice and their wildtype (Crh + / +) littermates in the CFA (Complete Freund’s Adjuvant)-induced inflammatory pain model. Pain thresholds were evaluated with the Hargreaves apparatus.

Results

Our experiments showed that Crh deficiency led to increased pain response, which was associated with decreased POMC mRNA levels in locally inflamed paws of these mice. Furthermore, Crh-/- mice had higher paw edema than Crh + / + mice. Histological evaluation of inflamed paw tissues revealed increased inflammatory response in Crh-/- mice. Protein levels of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β, were higher in inflamed tissue of Crh-/- mice compared to wildtype mice. Corticosterone replacement increased the pain threshold of Crh-/- mice, restored their paw volume to the levels of wildtype mice, and significantly reduced their proinflammatory cytokine levels. Furthermore, glucocorticoid administration significantly increased POMC mRNA expression in the inflamed paw.

Conclusion

Our data suggest that genetic deficiency of CRH is associated with increased pain. This effect is likely attributable to the accompanying glucocorticoid insufficiency and is in part mediated by opioids expressed locally.

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Title: Corticotropin-releasing hormone deficiency results in impaired analgesic response during CFA-induced inflammation
Authors: Efthymia Karagianni
Olga Rassouli
Smaragda Poulaki
Eirini Dermitzaki
George Liapakis
Andrew N. Margioris
Maria Venihaki
Publication date: 14-05-2024
Publisher: Springer International Publishing
Keywords: Glucocorticoid
Cytokines
Opioids
Opioids
Published in: Hormones
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-024-00565-8

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