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

Abstract

(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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“…28 A previous study has shown that it has the potential as an analgesic to ameliorate visceral sensitivity and reduce abdominal pain. 29 Bojungikgi-tang is a traditional oriental herbal formula comprising eight medicinal herbs. It has been used to treat gastric disorders, such as gastric atony, smooth muscle asthenia, and stomach muscle asthenia.…”

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“…Ojeok-san (OJS) is a herbal formula [ 14 , 15 ] used in Asian countries, such as Korea, Japan, China, etc. for the treatment of depression, gastrointestinal tract and pain.…”

“…[ 16 ] reported that OJS can reduce the number of inflammation-related factors in bronchoalveolar lavage fluid, such as interleukin-4, immunoglobulin, etc., and reduce the infiltration of inflammatory cells in the respiratory tract and inhibit pulmonary fibrosis. OJS can also reduce the feeling of mechanical injury induced by interleukin-10 knockout mice and improve the pain-like behaviour of inflammatory bowel disease model [ 15 ]. In a colitis-induced colorectal cancer mouse model, OJS can reduce the pain perception of visceral and physical injuries in mice [ 17 ].…”