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Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model

Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OA pain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) system in pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). The effect of a PK an...

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Autores principales: Galimberti, Giulia, Amodeo, Giada, Magni, Giulia, Riboldi, Benedetta, Balboni, Gianfranco, Onnis, Valentina, Ceruti, Stefania, Sacerdote, Paola, Franchi, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526764/
https://www.ncbi.nlm.nih.gov/pubmed/37759478
http://dx.doi.org/10.3390/cells12182255
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author Galimberti, Giulia
Amodeo, Giada
Magni, Giulia
Riboldi, Benedetta
Balboni, Gianfranco
Onnis, Valentina
Ceruti, Stefania
Sacerdote, Paola
Franchi, Silvia
author_facet Galimberti, Giulia
Amodeo, Giada
Magni, Giulia
Riboldi, Benedetta
Balboni, Gianfranco
Onnis, Valentina
Ceruti, Stefania
Sacerdote, Paola
Franchi, Silvia
author_sort Galimberti, Giulia
collection PubMed
description Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OA pain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) system in pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). The effect of a PK antagonist (PC1) was compared to that of diclofenac. C57BL/6J male mice injected with MIA in the knee joint were characterized by allodynia, motor deficits, and fatigue. Twenty-eight days after MIA, in the knee joint, we measured high mRNA of PK2 and its receptor PKR1, pro-inflammatory cytokines, and MMP13. At the same time, in the sciatic nerve and spinal cord, we found increased levels of PK2, PKR1, IL-1β, and IL-6. These changes were in the presence of high GFAP and CD11b mRNA in the sciatic nerve and GFAP in the spinal cord. OA mice were also characterized by anxiety, depression, and neuroinflammation in the prefrontal cortex and hippocampus. In both stations, we found increased pro-inflammatory cytokines. In addition, PK upregulation and reactive astrogliosis in the hippocampus and microglia reactivity in the prefrontal cortex were detected. PC1 reduced joint inflammation and neuroinflammation in PNS and CNS and counteracted OA pain and emotional disturbances.
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spelling pubmed-105267642023-09-28 Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model Galimberti, Giulia Amodeo, Giada Magni, Giulia Riboldi, Benedetta Balboni, Gianfranco Onnis, Valentina Ceruti, Stefania Sacerdote, Paola Franchi, Silvia Cells Article Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OA pain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) system in pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). The effect of a PK antagonist (PC1) was compared to that of diclofenac. C57BL/6J male mice injected with MIA in the knee joint were characterized by allodynia, motor deficits, and fatigue. Twenty-eight days after MIA, in the knee joint, we measured high mRNA of PK2 and its receptor PKR1, pro-inflammatory cytokines, and MMP13. At the same time, in the sciatic nerve and spinal cord, we found increased levels of PK2, PKR1, IL-1β, and IL-6. These changes were in the presence of high GFAP and CD11b mRNA in the sciatic nerve and GFAP in the spinal cord. OA mice were also characterized by anxiety, depression, and neuroinflammation in the prefrontal cortex and hippocampus. In both stations, we found increased pro-inflammatory cytokines. In addition, PK upregulation and reactive astrogliosis in the hippocampus and microglia reactivity in the prefrontal cortex were detected. PC1 reduced joint inflammation and neuroinflammation in PNS and CNS and counteracted OA pain and emotional disturbances. MDPI 2023-09-12 /pmc/articles/PMC10526764/ /pubmed/37759478 http://dx.doi.org/10.3390/cells12182255 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Galimberti, Giulia
Amodeo, Giada
Magni, Giulia
Riboldi, Benedetta
Balboni, Gianfranco
Onnis, Valentina
Ceruti, Stefania
Sacerdote, Paola
Franchi, Silvia
Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title_full Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title_fullStr Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title_full_unstemmed Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title_short Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model
title_sort prokineticin system is a pharmacological target to counteract pain and its comorbid mood alterations in an osteoarthritis murine model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526764/
https://www.ncbi.nlm.nih.gov/pubmed/37759478
http://dx.doi.org/10.3390/cells12182255
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