Volume 25 Issue 4 - November 22, 2013 PDF
Impairment of long-term depression in the anterior cingulate cortex of mice with bone cancer pain
Chiuan-Shiou Chiou1,2, Chiung-Chun Huang3, Ying-Ching Liang3,Yu-Chuan Tsai2, Kuei-Sen Hsu1,3,*
1 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
2 Department of Anesthesiology, National Cheng Kung University Hospital, Tainan 704, Taiwan
3 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
Font Enlarge
Pain often accompanies cancer and has a major impact on the survival and quality of life for cancer patients. It is estimated that 75%-90% of patients with metastatic or advanced stage cancer experience significant cancer-induced pain. Although various complementary therapies, including radiotherapy, chemotherapy and treatment with bisphosphonates and analgesics, have been used to treat bone pain, many patients with bone cancer pain report limited pain relief and adverse side effects. Therefore, the development of more effective mechanism-based therapies to treat this debilitating pain is urgently needed.

So far, little is known about the molecular mechanisms involved in the development and maintenance of bone cancer pain. In this study, we have identified the impairments of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses and long-term depression (LTD) in rostral anterior cingulate cortex (rACC) neurons from mice with bone cancer pain. Moreover, we show that there was a significant decrease in NMDA receptor subunit protein expression in the rACC of tumor-bearing mice. The current results indicate that tumor-induced injury or remodeling of primary afferent sensory nerve fibers that innervate the tumor-bearing bone may cause a persistent decrease in NMDA receptor expression in rACC neurons, resulting in a loss of LTD induction, thereby leading to long-term alterations of rACC activity and creating exaggerated pain behaviors. This study may shed light on the central mechanism of bone cancer pain and provide a novel therapeutic strategy for prevention or treatment of bone cancer pain by focusing on the plastic changes occurring at rACC synapses.

Figure 1. Elevation of pCREB expression in the rACC of tumor-bearing mice. Representative images with immunofluorescent staining showing expression of pCREB in the coronal rACC sections from sham-operated and tumor-bearing mice at different time points after operation.
< Previous
Next >
Copyright National Cheng Kung University