Pain Signaling Study Published in PNAS

Postoperative pain is a common complication of surgery that may contribute to delirium and memory dysfunction, especially in the elderly. To better understand the connection between postoperative pain and cognitive dysfunction, Duke Anesthesiology’s Niccolò Terrando, PhD, and his colleagues, studied pain behavior and nerve injury biomarker expression in mice undergoing orthopedic surgery to repair fractured bones.

Professor Tomas Hökfelt

Professor Tomas Hökfelt

Dr. Terrando and Professor Tomas Hökfelt of the Karolinska Institutet are co-senior authors of a manuscript published in the October 2016 issue of Proceedings of the National Academy of Sciences of the United States of America (PNAS), titled “Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels.” This study is also featured on PNAS’ research highlights page.

Using an established mouse bone-fracture model associating with memory deficits, Dr. Terrando and his collaborators (including the chairman of Duke Anesthesiology, Dr. Joseph Mathew, and Dr. Beilei Lei of Duke Anesthesiology’s Neuroinflammation and Cognitive Dysfunction Laboratory) assessed pain behavior and expression of several molecules in sensory neurons, spinal cord and brain. An increase in cold sensitivity and up-regulation of several injury markers, including activating transcription factor 3, the neuropeptide galanin, and growth factor brain-derived neurotrophic factor (BDNF), were observed in sensory ganglia. In the hippocampus, BDNF protein levels were increased in mossy fibers. In contrast, the BDNF transcript was not increased in the parent granule cell bodies, and c-Fos levels were decreased, as was neurogenesis.

Brain BDNF expression in control mouse (Left) and following orthopedic surgery (Right).

Brain BDNF expression in control mouse (Left) and following orthopedic surgery (Right).

According to the authors, results of this study reveal that impaired BDNF signaling and reduced neurogenesis in the hippocampus may contribute to mental deficits observed after surgery.

Drs. Terrando and Mathew are both notably DREAM Innovation Grant (DIG) recipients. DIGs support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management research. Dr. Terrando received the award in 2016 for his project, titled “The Systemic Milieu and its Role in Postoperative Cognitive Dysfunction.” Dr. Mathew received a DIG in 2011 for his project, titled “Functional Neuroimaging to Assess Cognitive Function after Cardiac Surgery.” The DIG awards are made possible by Duke Anesthesiology’s DREAM Campaign which was established in 2007 to support the department’s research programs and initiatives.