NTU discovered why the cancer pain-killer medicine is decreasing its function, inspiring new drug development In clinical practice, patients’ tolerance towards pain-killer opioid medicines is always a tough issue. Especially for severe cancer patients, to sooth their severe cancer pain, the long-term, increase, use of opioid pain-killer, however, inevitably leads to the decrease of its efficacy. In order to improve the quality of clinical treatment, and to investigate the physiological reaction towards opioid pain-killer, the research team led by Dr. Chih-Peng Lin, Prof. Wei-Zen Sun and Prof. Wen-Mei Fu at National Taiwan University College of Medicine has devoted to this topic for more than three years. They discovered a cytokine in cancer patients’ central nervous system: CXCL1, a signalling protein created by cells, influencing the effect of opioid pain-killer. This discovery might inspire new drug development, which can inhibit the effect of CXCL1, and stabilize the effect of opioid pain-killer. This research is accepted and published by the most reputational medical journal in anesthesia discipline: Anesthesiology, in 2015. Firstly, the research team compared two groups of samples: opioid-tolerant cancer patients and opioid-naive subjects, to study their cerebrospinal fluid levels. It was found that the CXCL1 level in cerebrospinal fluid was significantly higher in the opioid-tolerant group. Besides, the CXCL1 level in cancer patients rose with the increase use of opioid dosage. Secondly, the research team then conduct animal experiments to prove their findings. On the one hand, after injecting opioid pain-killer into the spines of rats, the CXCL1 level in the spinal fluid of the injected rats increased significantly within 48 hours; on the other hand, providing the rats with CXCL1 antibody, which neutralizes the effect of CXCL1, would enhance the performance of the opioid pain-killer in the rats. As a result, CXCL1 is an important substance affecting the live organisms’ tolerance towards the opioid pain-killer; it is found in both opioid-tolerant patients and rats. Dr. Lin and Prof. Sun have dedicated themselves to improving and innovating the treatment for soothing the cancer pain for many years. In this research, they are responsible for clinical care, the collection of cerebrospinal fluid and data analysis. Meanwhile, the pharmacology team led by Prof. Fu specializes in animal experiment and new drug development. It is their expertise and teamwork that achieves this crucial study. Because the CXCL1 signal pathway may be a novel target for the treatment of opioid tolerance, and inspires future drug development, this study was elected by the American Society of Anesthesiologists (ASA) as the most important scientific discovery of the issue. It is a research that has both scientific contribution and societal benefits. Hence, ASA disseminated this study widely in both the scientific community and the media. For example, this scientific breakthrough was published on the website of Forbes as well. Reference Chih-Peng Lin, M.D., Kai-Hsiang Kang, Ph.D., Tzu-Hung Lin, Ph.D., Ming-Yueh Wu, Ph.D., Houng- Chi Liou, M.S., Woei-Jer Chuang, Ph.D., Wei-Zen Sun, M.D., Wen- Mei Fu, Ph.D.; Role of Spinal CXCL1 (GROα) in Opioid Tolerance: A Human-to-rodent Translational Study. Anesthesiology 2015; 122(3):666-676. DOI:10.1097/ ALN.0000000000000523. Professor Wen-Mei Fu Department of Pharmacology wenmei@ntu.edu.tw Professor Wei-Zen Sun Department of Anesthesiology wzsun@ntu.edu.tw