Inflammatory mechanisms of pain sensitization
Peripheral inflammatory processes, induced by bacterial infections or resulting from disease-related changes in the intestinal barrier, are associated with the release of pro-inflammatory immune mediators. These mediators, especially pro-inflammatory cytokines, not only regulate the peripheral inflammatory response during an acute infection, but can also reach the brain via vagal, spinal and humoral mechanisms. The “sickness response” that is elicited by these afferent immune-to-brain pathways is characterized by a range of physiological and psychological symptoms, including changes in behavior, mood and pain. We aim to elucidate the neurobiological mechanisms of pain sensitization in the context of acute and chronic inflammation, and to unravel how inflammation interacts with mood changes to enhance responses to pain and other somatic symptoms.
To do so, we apply behavioral and brain imaging approaches in healthy men and women during experimental endotoxemia. In addition, we analyze the neuroendocrine regulation of peripheral immune cells in patients with chronic inflammatory diseases. The results contribute to a better understanding of the pathophysiology of acute and chronic pain, especially with regard to the importance of inflammatory mechanisms and neuroendocrine-immune interactions.
Benson Sven, Clinic of Neurology
Dr. A. Wegner, Prof. Dr. M. Jäger, Trauma and Orthopedic Surgery, Essen University Hospital
Prof. Dr. O. Witzke, Prof. Dr. A. Kribben, Infectiology and Nephrology, Essen University Hospital
Prof. Dr. M. Forsting, Diagnostic and Interventional Radiology and Neuroradiology, Essen University Hospital
PD Dr. Karsten Wrede, Neurosurgery, Essen University Hospital
Dr. I. Spreitzer, Paul Ehrlich Institute, Federal Agency for Sera and Vaccines, Langen
Prof. Dr. J. Langhorst, Integrative Gastroenterology, Kliniken Essen-Mitte
Prof. Dr. M. Lekander, Department of Clinical Neuroscience, Karolinska Institutet, Sweden
Dr. Marcello Costantini, Centre for Brain Science, Department of Psychology, University of Essex, United Kingdom.
German Research Foundation (DFG):
BE 5173/2-1 and EL 236/11-1 „Effects of experimental endotoxemia on the neural processing of visceral and somatosensory stimuli“
Benson S, Engler H, Wegner A, Rebernik L, Spreitzer I, Schedlowski M, Elsenbruch S
What makes you feel sick after inflammation? Predictors of acute and persisting physical sickness symptoms induced by experimental endotoxemia
Clin Pharmacol Ther, 2017 Jan 11. doi: 10.1002/cpt.618. Epub ahead of print
Lasselin J, Elsenbruch S, Lekander M, Axelsson J, Karshikoff B, Grigoleit JS, Engler H, Schedlowski M, Benson S.
Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior.
Brain Behav Immun. 2016;57:30-37
Labrenz F, Wrede K, Forsting M, Engler H, Schedlowski M, Elsenbruch S, Benson S.
Alterations in functional connectivity of resting state networks during experimental endotoxemia - An exploratory study in healthy men.
Brain Behav Immun. 2016;52:18-26
Engler H, Benson S, Wegner A, Spreitzer I, Schedlowski M, Elsenbruch S.
Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms.
Brain Behav Immun 2016;52:18-26.
Wegner A, Elsenbruch S, Rebernik L, Roderigo T, Engelbrecht E, Jäger M, Engler H, Schedlowski M.
Inflammation-induced pain sensitization in men and women: Does sex matter in experimental endotoxemia?
Benson S, Rebernik L, Wegner A, Kleine-Borgmann J, Engler H, Schlamann M, Forsting M, Schedlowski M, Elsenbruch S.
Neural circuitry mediating inflammation-induced central pain amplification in human experimental endotoxemia.
Brain Behav Immun 2015;48:222-31.
Wegner A, Elsenbruch S, Maluck J, Grigoleit JS, Engler H, Jäger M, Spreitzer I, Schedlowski M, Benson S
Inflammation induced hyperalgesia: Effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.
Brain, Behavior, and Immunity 2014 Oct: 41;46-54.