Metformin relieves bone cancer pain by reducing TGFβRI-TRPV1 signaling in rats
Fang Zhou,
He-Ya Qian,
Ke Wang,
Yong-Juan Gu,
Pei-Lin Liu,
Ling Zhang,
Long Chen,
Yu Song,
Ya-Nan Chen,
Hai-Long Zhang
Affiliations
Fang Zhou
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
He-Ya Qian
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Ke Wang
Department of Pain, Suzhou Wuzhong People's Hospital, Suzhou 215128, China
Yong-Juan Gu
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Pei-Lin Liu
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Ling Zhang
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Long Chen
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Yu Song
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China
Ya-Nan Chen
Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China; Corresponding author. Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China.
Hai-Long Zhang
Center of Translational Medicine and Clinical Laboratory, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215123, China; Corresponding author. Center of Translational Medicine, Medical Center of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215123, China.
Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.
