Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer.
Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CA...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0270338 |
| _version_ | 1811294909337960448 |
|---|---|
| author | Patrice Cunningham Aman Sumal Emma Patton Henry Helms Matthew T Noneman Gustavo Martinez-Muñiz Jackie E Bader Ioulia Chatzistamou Ahmed Aladhami Christian Unger Reilly T Enos Hyeun Kyoo Shin Kandy T Velázquez |
| author_facet | Patrice Cunningham Aman Sumal Emma Patton Henry Helms Matthew T Noneman Gustavo Martinez-Muñiz Jackie E Bader Ioulia Chatzistamou Ahmed Aladhami Christian Unger Reilly T Enos Hyeun Kyoo Shin Kandy T Velázquez |
| author_sort | Patrice Cunningham |
| collection | DOAJ |
| description | Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia. |
| first_indexed | 2024-04-13T05:24:31Z |
| format | Article |
| id | doaj.art-2d4c12ffc6864f81a4637254c96d5a27 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T05:24:31Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2d4c12ffc6864f81a4637254c96d5a272022-12-22T03:00:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e027033810.1371/journal.pone.0270338Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer.Patrice CunninghamAman SumalEmma PattonHenry HelmsMatthew T NonemanGustavo Martinez-MuñizJackie E BaderIoulia ChatzistamouAhmed AladhamiChristian UngerReilly T EnosHyeun Kyoo ShinKandy T VelázquezCancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia.https://doi.org/10.1371/journal.pone.0270338 |
| spellingShingle | Patrice Cunningham Aman Sumal Emma Patton Henry Helms Matthew T Noneman Gustavo Martinez-Muñiz Jackie E Bader Ioulia Chatzistamou Ahmed Aladhami Christian Unger Reilly T Enos Hyeun Kyoo Shin Kandy T Velázquez Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. PLoS ONE |
| title | Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. |
| title_full | Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. |
| title_fullStr | Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. |
| title_full_unstemmed | Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. |
| title_short | Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer. |
| title_sort | ojeok san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer |
| url | https://doi.org/10.1371/journal.pone.0270338 |
| work_keys_str_mv | AT patricecunningham ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT amansumal ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT emmapatton ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT henryhelms ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT matthewtnoneman ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT gustavomartinezmuniz ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT jackieebader ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT iouliachatzistamou ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT ahmedaladhami ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT christianunger ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT reillytenos ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT hyeunkyooshin ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer AT kandytvelazquez ojeoksanamelioratesvisceralandsomaticnociceptioninamousemodelofcolitisinducedcolorectalcancer |