USP48 alleviates bone cancer pain and regulates MrgC stabilization in spinal cord neurons of male mice

Abstract

Bone cancer pain (BCP), as a common type of cancer pain, is a specific pain state that differs from inflammatory pain and neuropathic pain (Gadepalli et al., 2021). BCP brings a series of adverse effects, including nausea and vomiting, loss of appetite, anxiety, depression, fear and helplessness, which make the patients suffer (Sung et al., 2021). With advances in medical technology, most patients with malignancies have significantly longer survival (Sung et al., 2021). However, the bone disease and pain associated with metastatic cancer has yet to be addressed. The development of new therapeutic approaches and drug targets for BCP is, therefore, particularly urgent.Mas-related G protein-coupled receptor C (MrgC) is a member of the Mrg receptor family that are expressed in small-diameter primary sensory neurons. The activation of MrgC can inhibit a variety of pains including inflammatory pain, neuropathic pain and BCP (He et al., 2014;Jiang et al., 2013;Sun, Zhang, et al., 2016). Our previous studies have shown that MrgC plays an important role in the development of BCP, and can inhibit Ca2+ inward