Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases

(1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an “inactive” state experience abdominal pain. The medicinal...

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Main Authors: Emma A. Patton, Patrice Cunningham, Matthew Noneman, Henry P. Helms, Gustavo Martinez-Muniz, Aman S. Sumal, Milan K. Dhameja, Christian A. Unger, Ahmed K. Alahdami, Reilly T. Enos, Ioulia Chatzistamou, Kandy T. Velázquez
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/7/1559
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author Emma A. Patton
Patrice Cunningham
Matthew Noneman
Henry P. Helms
Gustavo Martinez-Muniz
Aman S. Sumal
Milan K. Dhameja
Christian A. Unger
Ahmed K. Alahdami
Reilly T. Enos
Ioulia Chatzistamou
Kandy T. Velázquez
author_facet Emma A. Patton
Patrice Cunningham
Matthew Noneman
Henry P. Helms
Gustavo Martinez-Muniz
Aman S. Sumal
Milan K. Dhameja
Christian A. Unger
Ahmed K. Alahdami
Reilly T. Enos
Ioulia Chatzistamou
Kandy T. Velázquez
author_sort Emma A. Patton
collection DOAJ
description (1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an “inactive” state experience abdominal pain. The medicinal herb Ojeok-san (OJS) has shown promise in the amelioration of visceral pain. However, no research on OJS has been conducted in preclinical models of IBD. The mechanism by which OJS promotes analgesia is still elusive, and it is unclear if OJS possesses addictive properties. (2) Aims: In this study, we examined the potential of OJS to promote analgesic effects and rewarding behavior. Additionally, we investigated if tumor necrosis factor alpha (TNFα) from macrophages is a primary culprit of IBD-induced nociception. (3) Methods: Multiple animal models of IBD were used to determine if OJS can reduce visceral nociception. TNFα-macrophage deficient mice were used to investigate the mechanism of action by which OJS reduces nociceptive behavior. Mechanical sensitivity and operant conditioning tests were used to determine the analgesic and rewarding effects of OJS. Body weight, colon length/weight, blood in stool, colonic inflammation, and complete blood count were assessed to determine disease progression. (4) Results: OJS reduced the evoked mechanical nociception in the dextran sulphate sodium model of colitis and IL-10 knockout (KO) mice and delayed aversion to colorectal distension in C57BL/6 mice. No rewarding behavior was observed in OJS-treated IL-10 KO and mdr1a KO mice. The analgesic effects of OJS are independent of macrophage TNFα levels and IBD progression. (5) Conclusions: OJS ameliorated elicited mechanical and visceral nociception without producing rewarding effects. The analgesic effects of OJS are not mediated by macrophage TNFα.
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spelling doaj.art-def57144b3894acd8553994925db2ddd2023-11-17T17:18:42ZengMDPI AGNutrients2072-66432023-03-01157155910.3390/nu15071559Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel DiseasesEmma A. Patton0Patrice Cunningham1Matthew Noneman2Henry P. Helms3Gustavo Martinez-Muniz4Aman S. Sumal5Milan K. Dhameja6Christian A. Unger7Ahmed K. Alahdami8Reilly T. Enos9Ioulia Chatzistamou10Kandy T. Velázquez11Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA(1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an “inactive” state experience abdominal pain. The medicinal herb Ojeok-san (OJS) has shown promise in the amelioration of visceral pain. However, no research on OJS has been conducted in preclinical models of IBD. The mechanism by which OJS promotes analgesia is still elusive, and it is unclear if OJS possesses addictive properties. (2) Aims: In this study, we examined the potential of OJS to promote analgesic effects and rewarding behavior. Additionally, we investigated if tumor necrosis factor alpha (TNFα) from macrophages is a primary culprit of IBD-induced nociception. (3) Methods: Multiple animal models of IBD were used to determine if OJS can reduce visceral nociception. TNFα-macrophage deficient mice were used to investigate the mechanism of action by which OJS reduces nociceptive behavior. Mechanical sensitivity and operant conditioning tests were used to determine the analgesic and rewarding effects of OJS. Body weight, colon length/weight, blood in stool, colonic inflammation, and complete blood count were assessed to determine disease progression. (4) Results: OJS reduced the evoked mechanical nociception in the dextran sulphate sodium model of colitis and IL-10 knockout (KO) mice and delayed aversion to colorectal distension in C57BL/6 mice. No rewarding behavior was observed in OJS-treated IL-10 KO and mdr1a KO mice. The analgesic effects of OJS are independent of macrophage TNFα levels and IBD progression. (5) Conclusions: OJS ameliorated elicited mechanical and visceral nociception without producing rewarding effects. The analgesic effects of OJS are not mediated by macrophage TNFα.https://www.mdpi.com/2072-6643/15/7/1559TNFαmechanical sensitivityaversionconditioning place preferencecolorectal distension
spellingShingle Emma A. Patton
Patrice Cunningham
Matthew Noneman
Henry P. Helms
Gustavo Martinez-Muniz
Aman S. Sumal
Milan K. Dhameja
Christian A. Unger
Ahmed K. Alahdami
Reilly T. Enos
Ioulia Chatzistamou
Kandy T. Velázquez
Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
Nutrients
TNFα
mechanical sensitivity
aversion
conditioning place preference
colorectal distension
title Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
title_full Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
title_fullStr Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
title_full_unstemmed Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
title_short Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases
title_sort acute administration of ojeok san ameliorates pain like behaviors in pre clinical models of inflammatory bowel diseases
topic TNFα
mechanical sensitivity
aversion
conditioning place preference
colorectal distension
url https://www.mdpi.com/2072-6643/15/7/1559
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