Mirogabalin improves cancer-associated pain but increases the risk of malignancy in mice with pancreatic cancer : PAIN

Journal Logo

Advanced Search
Research Paper

Mirogabalin improves cancer-associated pain but increases the risk of malignancy in mice with pancreatic cancer

Itaya, Tomoakia; Sano, Makotob,*; Kajiwara, Ichiea; Oshima, Yukinoa; Kuramochi, Tomoyaa; Kim, Jinsukb; Ichimaru, Yoshimic; Kitajima, Osamua; Masamune, Atsushid; Ijichi, Hideakie,f; Ishii, Yukimotob; Suzuki, Takahiroa

Author Information

aDepartment of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan

bDivision of Medical Research Planning and Development, Nihon University School of Medicine, Tokyo, Japan

cSchool of Pharmacy, Shonan University of Medical Sciences, Yokohama, Japan

dDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

eDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

fClinical Nutrition Center, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

*Corresponding author. Address: Division of Medical Research Planning and Development, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. Tel.: +81-3-3972-8111. E-mail address: [email protected] (M. Sano).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

PAIN 164(7):p 1545-1554, July 2023. | DOI: 10.1097/j.pain.0000000000002852

Mirogabalin, a selective voltage-gated calcium channel α2δ ligand, improves peripheral neuropathic pain; however, its effects on patients with cancers including pancreatic ductal adenocarcinoma (PDAC) remain unknown. We analyzed the effects of mirogabalin on a KPPC (LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+) mouse model of PDAC. Six-week-old KPPC mice received oral mirogabalin (10 mg/kg/day) (n = 10) or vehicle water (n = 14) until the humane end point. Cancer-associated pain was evaluated using the scores of hunching and mouse grimace scale (MGS). Tumor status and plasma cytokine levels were determined using histopathological analysis and cytokine array, respectively. The effects of mirogabalin on the proliferative ability of PDAC cell lines were determined. The scores of the hunching and MGS improved after mirogabalin administration with a decrease in the plasma levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interferon-γ. Although no significant difference in the survival rate was observed, mirogabalin significantly increased pancreatic tumor size and proliferative index of Ki-67 and cyclins. Local arginase-1+ M2-like tumor-associated macrophages and CD31+ tumor blood vessels increased after mirogabalin administration. By contrast, the number of α-smooth muscle actin+ cancer-associated fibroblasts, desmoplastic stroma, and CD8+ T cells decreased. Local myeloperoxidase+ tumor-associated neutrophils and CD45R+ B cells were unaltered. Mirogabalin enhanced the proliferative ability of PDAC cell lines with the upregulation of cyclins and cyclin-dependent kinases; however, it inhibited the potential of pancreatic stellate cells in vitro. Therefore, our results suggest that mirogabalin improves cancer-associated pain but enhances the proliferative potential of PDAC in vitro and in vivo.

© 2023 International Association for the Study of Pain

Full Text Access for Subscribers:

Log in here >
IASP Members
Log in here >

Not a Subscriber?

Buy
Request Permissions

You can read the full text of this article if you:

Access through Ovid