Mirogabalin是一种选择性电压门控钙通道α2δ配体，能够改善外周神经病理性疼痛；但是，它对包括胰管腺癌（PDAC）在内的癌症患者的影响尚不清楚。我们分析了Mirogabalin在PDAC的LSL-KrasG12D / +；Trp53flox / flox；Pdx-1cre / +小鼠模型中的影响。六周大的KPPC小鼠接受口服Mirogabalin（10mg / kg / day）（n = 10）或车载水（n = 14），直到人道终点。使用驼背和小鼠面部表情评分法评估与癌症相关的疼痛。使用组织病理学分析和细胞因子芯片确定肿瘤状态和血浆细胞因子水平。测定Mirogabalin对PDAC细胞系增殖能力的影响。在Mirogabalin治疗后，驼背和小鼠面部表情评分提高，炎性细胞因子，如肿瘤坏死因子-α，白细胞介素-6和干扰素-γ的血浆水平降低。虽然未观察到存活率的显著差异，但Mirogabalin显著增加胰腺肿瘤大小和Ki-67和环蛋白的增殖指数。Mirogabalin治疗后，当地的精氨酸酶-1 + M2型肿瘤相关巨噬细胞和CD31 +肿瘤血管增加。相反，α平滑肌肌动蛋白弱阳性癌相关成纤维细胞的数量、纤维化基质和CD8 + T细胞减少。当地的髓过氧化物酶+肿瘤相关中性粒细胞和CD45R + B细胞没有改变。Mirogabalin通过上调环蛋白和CDK的表达增强了PDAC细胞系的增殖能力；然而，它抑制了胰星状细胞的潜力。因此，我们的结果表明Mirogabalin能够改善癌症相关的疼痛，但在体内和体外下增强PDAC的增殖潜力。 版权所有©2022国际疼痛研究协会。

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 endpoint. 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. In contrast, the number of α-smooth muscle actin weak+ 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 CDKs; 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 .Copyright © 2022 International Association for the Study of Pain.