Research Focus

Mechanisms of perception: from pleasant touch to the experience of pain

Our research on perception covers the neurobiological basis and clinical implications of both pleasant and aversive perceptions. Positive perceptions, especially hugs and other pleasant touches, can not only reduce stress but also have a pain-relieving effect. We investigate the neurobiological mechanisms of these stress-protective and anti-nociceptive effects of social touch in experimental studies in the laboratory and with ambulatory assessments in everyday life. Our work on aversive perception focuses on pain as a core symptom in many health conditions. We are particularly interested in perceptions from the inside of the body, also known as "interoception", which are crucial for visceral pain and disorders involving the gut-brain axis. As part of our DFG-funded work within the Collaborative Research Center SFB 1280 'Extinction Learning', we focus primarily on interfaces of interoception with emotions (subproject A10, led by S. Elsenbruch & A. Icenhour) and inflammatory mechanisms underlying pain amplification (subproject A12, led by H. Engler & S. Elsenbruch) in studies with both healthy individuals and patients with chronic abdominal pain. Utilizing an enhanced comprehension of the underlying mechanisms, we explore novel approaches for preventing and treating chronic pain and stress-related health conditions.

Selected publications:

Packheiser, J*, Hartmann, H*, Gazzola, V, Keysers, C, Michon, F (2024). A systematic review and multivariate meta-analysis of the physical and mental health benefits of touch interventions. Nat Hum Behav; Apr 8. doi: 10.1038/s41562-024-01841-8. Online ahead of print[*shared authorship ]

Öhlmann H, Lanters LR, Theysohn N, Langhorst J, Engler H, Icenhour A, Elsenbruch S (2023). Distinct Alterations in Central Pain Processing of Visceral and Somatic Pain in Quiescent Ulcerative Colitis Compared to Irritable Bowel Syndrome and Health. J Crohns Colitis; 17(10):1639-1651.

Benson S, Labrenz F, Kotulla S, Brotte L, Rödder P, Tebbe B, Theysohn N, Engler H, Elsenbruch S (2023). Amplified gut feelings under inflammation and depressed mood: A randomized fMRI trial on interoceptive pain in healthy volunteers. Brain Behav Immun; 112:132-137.

Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B (2022). A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology; 162(1):300-315.

Kreuder AK, Scheele D, Wassermann L, Wollseifer M, Stoffel-Wagner B, Lee M, Hennig J, Maier W, Hurlemann R (2017) How the brain codes intimacy: The neurobiological substrates of romantic touch. Hum Brain Mapp; 38: 4525-4534. 

Mechanisms and clinical relevance of the central fear network: from fear learning to pain memory

One of our research goals is to gain a deeper understanding of the functioning of the central fear network in the brain. The amygdala and hippocampus, with their multiple connections to other brain regions, are considered central structures for emotional learning and memory processes. This understanding is crucial for the development of new treatments for conditions associated with stress and fear, such as chronic pain. We investigate how individual learning experiences shape pain-related conditioned fear and how fear influences pain perception. We also focus on avoidance behavior as an important behavioral consequence of fear. In the realm of innovative behavioral approaches to pain therapy, we analyze the mechanisms of extinction learning, in particular the role of stress and inflammatory mediators in the context of inflammatory bowel diseases and irritable bowel syndrome and other chronic visceral pain conditions. This research is funded by the DFG as part of the Collaborative Research Center SFB 1280 'Extinction Learning' in the subprojects A10 (PIs: S. Elsenbruch & A. Icenhour) and A12 (PIs: H. Engler & S. Elsenbruch).

Selected publications:

Pawlik RJPetrakova L, Cueillette A, Krawczyk K, Theysohn N, Elsenbruch S, Engler H (2023). Inflammation shapes neural processing of interoceptive fear predictors during extinction learning in healthy humans. Brain Behav Immun; 108:328-339.

Morr M, Noell J, Sassin D, Daniels J, Philipsen A, Becker B, Stoffel-Wagner B, Hurlemann R, Scheele D (2022). Lonely in the Dark: Trauma Memory and Sex-Specific Dysregulation of Amygdala Reactivity to Fear Signals. Adv Sci (Weinh); 9(15):e2105336.

Icenhour A, Petrakova L, Hazzan N, Theysohn N, Merz CJ, Elsenbruch S (2021). When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm. Neuroimage; 238:118229.

Koenen LR, Pawlik RJ, Icenhour A, Petrakova L, Forkmann K, Theysohn N, Engler H, Elsenbruch S (2021). Associative learning and extinction of conditioned threat predictors across sensory modalities. Commun Biol; 4(1):553.

Kreuder AK, Scheele D, Schultz J, Hennig J, Marsh N, Dellert T, Ettinger U, Philipsen A, Babasiz M, Herscheid A, Remmersmann L, Stirnberg R, Stöcker T, Hurlemann R (2020). Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear. Proc Natl Acad Sci USA; 117(21):11781-11787.

Cognitive pain modulation through treatment expectations: Placebo and nocebo effects

Treatment expectations influence the perception of bodily symptoms, including pain. Our research projects aim to elucidate the psychological and neurobiological mechanisms of positive (placebo) and negative (nocebo) expectation effects, with a focus on visceral pain and interoceptive symptoms involving the gut-brain axis. On the one hand, the aim is to bring knowledge about positive expectation effects into clinical application. On the other hand, the role of negative expectations in symptom persistence and treatment discontinuation should also be clarified to minimize nocebo effects in everyday clinical practice. We combine experimental research with clinical studies, particularly aiming to improve the treatment of postoperative pain and chronic abdominal pain. This research is funded by the DFG as part of the Transregional Collaborative Research Center TRR 289 'Treatment Expectation' in subproject A04 (PI: S. Elsenbruch).

Selected publications:

Benson S, Labrenz F, Kotulla S, Brotte L, Rödder P, Tebbe B, Theysohn N, Engler H, Elsenbruch S (2023). Amplified gut feelings under inflammation and depressed mood: A randomized fMRI trial on interoceptive pain in healthy volunteers. Brain Behav Immun; 112:132-137.

Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B (2022). A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology; 162(1):300-315.

Bosman M, Elsenbruch S, Corsetti M, Tack J, Simrén M, Winkens B, Boumans T, Masclee A, Keszthelyi D (2021). The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol; 6(6):459-473.

Elsenbruch S, Enck P (2015). Placebo effects and their determinants in gastrointestinal disorders. Nat Rev Gastroenterol Hepatol; 12:472-485.

Social bonding and loneliness

Why do some people thrive in a social environment and benefit from social interactions, while others become socially isolated and lonely? How does social contact, or the lack thereof, affect our brains and shape our social perception and memory? It is well established that social isolation and loneliness have devastating consequences for physical and mental well-being, but the specific neural and hormonal mechanisms underlying these deleterious effects are still unclear. We therefore investigate the determinants and consequences of social attachment in healthy adults and patients with mental disorders. In parallel, we aim to better understand how interpersonal touch as a powerful means of communicating feelings is also crucial for maintaining social bonds. We are particularly interested in how interindividual differences such as gender and early life experiences modulate the processing of social touch and the neurobiological substrates of social bonding. This research is funded by a DFG grant (Head: D. Scheele).

Selected publications:

Berger R, Hurlemann R, Shamay-Tsoory S, Kanterman A, Brauser M, Gorni J, Luhmann M, Schramm E, Schultz J, Philipsen A, Lieberz J, Scheele D (2024). Oxytocin-augmented modular-based group intervention for loneliness: A proof-of-concept randomized-controlled trial. Psychotherapy & Psychosomatics (in press).

Lieberz J, Shamay-Tsoory SG, Saporta N, Kanterman A, Gorni J, Esser T, Kuskova E, Schultz J, Hurlemann R, Scheele D (2022) Behavioral and neural dissociation of social anxiety and loneliness. Journal of Neuroscience 42: 2570-2583.

Morr M, Liu X, Hurlemann R, Becker B, Scheele D (2022) Chronic loneliness: Neurocognitive mechanisms and interventions. Psychotherapy & Psychosomatics 91: 227-237.

Lieberz J, Shamay-Tsoory SG, Saporta N, Esser T, Kuskova E, Stoffel-Wagner B, Hurlemann R, Scheele D (2021) Loneliness and the social brain: how perceived social isolation impairs human interactions. Advanced Science 8: e2102076.

Stress and trauma

Stress and traumatic life events are risk factors for the occurrence and persistence of physical and psychological symptoms. Acute and chronic stress as well as negative emotions and maladaptive coping influence the perception and evaluation of symptoms. The recall and recounting of past pain episodes and the resulting distress are also modulated by stress. Furthermore, traumatic experiences can profoundly alter social bonds and affect not only interaction preferences but also the perception of social touch. We use a biopsychosocial stress model and combine pharmacological, psychological and questionnaire-based research approaches from biopsychology, psychoneuroendocrinology and -immunology as well as neuroscience to shed light on the significance of stress and trauma in all its facets for various basic and clinical research questions. Based on these findings, neurobiologically informed interventions will be developed to reduce the negative consequences of stress and trauma.

Selected publications:

Stevens L, Bregulla M, Scheele D (2024) Out of touch? How trauma shapes the experience of social touch – neural and endocrine pathways. Neurosci Biobehav Rev; Apr:159:105595. doi: 10.1016/j.neubiorev.2024.105595. Epub 2024 Feb 17.

Borawski J, Papadatou-Pastou M, Packheiser J, Ocklenburg S (2023). Handedness in post-traumatic stress disorder: A meta-analysis. Neurosci Biobehav Rev; 145:105009.

Labrenz F, Merz CJ, Icenhour A (2023). Connecting dots in disorders of gut-brain interaction: the interplay of stress and sex hormones in shaping visceral pain. Front Psychiatry; 14:1204136.

Icenhour A, Labrenz F, Roderigo T, Benson S, Elsenbruch S (2020) The Role of Chronic Stress in Normal Visceroception: Insights From an Experimental Visceral Pain Study in Healthy Volunteers. Front Psychiatry; 11:107.

Labanski A, Langhorst J, Engler H, Elsenbruch S (2020) Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology; 111:104501.

Maier A, Gieling C, Heinen-Ludwig C, Stefan V, Schultz J, Güntürkün O, Becker B, Hurlemann R, Scheele D (2020) Association of Childhood Maltreatment With Interpersonal Distance and Social Touch Preferences in Adulthood. Am J Psychiatry; 177: 37-46.

Benson S, Siebert C, Koenen LR, Engler H, Kleine-Borgmann J, Bingel U, Icenhour A, Elsenbruch S (2019) Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: A randomized-controlled study in healthy men and women. Pain; 160(8):1719-1728.