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

• Published in: Nutrients Vol. 15; no. 7; p. 1559
• Main Authors: Patton, Emma A, Cunningham, Patrice, Noneman, Matthew, Helms, Henry P, Martinez-Muniz, Gustavo, Sumal, Aman S, Dhameja, Milan K, Unger, Christian A, Alahdami, Ahmed K, Enos, Reilly T, Chatzistamou, Ioulia, Velázquez, Kandy T
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.03.2023; MDPI
• Subjects: Age; Analgesia; Analgesics; Animal models; Animals; Aversion; Blood; Blood tests; Body weight; Care and treatment; Colitis; Colitis - chemically induced; Colon; colorectal distension; Complications and side effects; conditioning place preference; Cytokines; Dextran; Dextran Sulfate - adverse effects; Dextrans; Disease; Disease Models, Animal; Distension; Experiments; Herbal medicine; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - pathology; Interleukin 10; Intestine; Length-weight relationships; Macrophages; Mechanical properties; mechanical sensitivity; Medical research; Medicine; Medicine, Botanic; Medicine, Herbal; Medicine, Oriental; Methods; Mice; Mice, Inbred C57BL; Mice, Knockout; Multidrug resistance; Operant conditioning; Pain; Pain perception; Pathogenesis; TNFα; Tumor Necrosis Factor-alpha - adverse effects; Tumor necrosis factor-α; United States; United States > US; aversion; colorectal distension; TNFα; conditioning place preference; mechanical sensitivity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15071559

(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.