Biology subjects

Pogatzki-Zahn, E. M.

Publications and source records attributed to Pogatzki-Zahn, E. M..

4 recordsLinked to original sources

bioRxiv2023

Distinct Functional cerebral Hypersensitivity networks during incisional and inflammatory pain in rats

Although the pathophysiology of pain has been investigated tremendously, there are still many open questions, especially with regard to specific pain entities and their pain-related symptoms. To increase the translational impact of (preclinical) animal pain neuroimaging studies, the use of disease-specific pain models, as well as relevant stimulus modalities, are critical. Yet, the challenges of identifying neuroimaging signatures at a pain entity- and modality-specific level are manifold. Therefore, we developed a comprehensive framework for brain network analysis in disease-specific pain models combining functional MRI with graph-theory and data classification by linear discriminant analysis. This enabled us to expand our knowledge of stimulus (mechanical vs. electrical) modality processing under incisional (INC) and pathogen-induced inflammatory (CFA) pain entities compared to acute pain conditions. In short, graph-theoretical analyses revealed distinct Network Signatures of Pain Hypersensitivity (NSPH) for INC and CFA, resulting in impaired discrimination of stimulus modalities in both pain models compared to control conditions (CTR). Such specific neuroimaging signatures are an important step toward identifying novel pain biomarkers for certain diseases and relevant outcomes to evaluate target engagement of novel therapeutic options, which ultimately can be translated to the clinic.

neuroscience↗

bioRxiv2022

BEHAVIOURAL VOLUNTARY AND SOCIAL BIOASSAYS ENABLING IDENTIFICATION OF COMPLEX AND SEX DEPENDENT PAIN- (-RELATED) PHENOTYPES IN RATS WITH BONE CANCER

Cancer-induced bone pain (CIBP) is a common and devastating symptom with limited treatment options in patients, significantly affecting their quality of life. To uncover the mechanisms underlying CIBP, using rodent models is the most common approach; however, the translation of results to the clinic may be hindered because the assessment of pain-related behavior is often based exclusively on reflexive-based methods, which are only partially indicative relevant pain in patients. In order to improve the accuracy and strength of the preclinical experimental model of CIBP in rodents, we used a battery of multimodal behavioral tests that were also aimed at identifying rodent-specific behavioral components by using a homecage monitoring assay (HCM). Rats of all sexes received an injection with either heat-deactivated (sham-group) or potent mammary gland carcinoma Walker 256 cells into the tibia. By integrating multimodal datasets, we assessed pain-related behavioral trajectories of CIBP-phenotype, including evoked and non-evoked based assays and HCM. Using principal component analysis (PCA), we discovered sex-specific differences in establishing the CIBP-phenotype, which occurred earlier (and different) in males. In addition, HCM phenotyping revealed the occurrence of sensory-affective states manifested by mechanical hypersensitivity in sham when housed with a tumor-bearing cagemate (CIBP) of the same sex. This multimodal battery allows an in-depth characterization of the CIBP-phenotype under social aspects in rats. The detailed, sex-specific, and rat-specific social phenotyping of CIBP enabled by PCA provides the basis for mechanism-driven studies to ensure robustness and generalisability of results and provide information for targeted drug development in the future.

cancer biology↗

bioRxiv2022

Experimenter familiarization is a crucial prerequisite for assessing behavioral outcomes and reduces stress in mice not only under chronic pain conditions

ABSTARCTRodent behavior is affected by different environmental conditions. These do not only comprise experimental and housing conditions but also familiarization with the experimenter. However, specific effects on pain-related behavior and chronic pain conditions have not been examined. Therefore, we aimed to investigate the impact of different housing conditions, inverted day-night cycles, and experimenter familiarization on male mice following peripheral neuropathy using the spared nerve injury (SNI) model. Using a multimodal approach, we evaluated evoked pain-related-, anxiety- and depression-like behavior, corticosterone metabolite levels and utilized an integrative approach for relative-severity-assessment. Different environmental conditions are represented by individually ventilated cages and standard open cages combined with a reversed day-night-light cycle and experimenter habituation, inducing differentially modulated multidimensional pain- and emotion-like phenotypes in SNI mice. In addition, familiarization reduced the stress level caused by behavioral tests. Although no environmental condition significantly modulated the severity in SNI mice, it influenced pain-affected phenotypes and is, therefore, crucial for designing and interpreting preclinical pain studies. Moreover, environmental conditions should be considered more in the reporting guidelines, described in more detail, and discussed as a potential influence on pain phenotypes.

animal behavior and cognition↗

bioRxiv2022

Species-specific cutaneous protein signatures upon incision injury and correlation with distinct pain-related phenotypes in humans

Pain after surgery is common, and its management remains a clinical challenge. Severe acute and prolonged post-surgical pain impairs immediate recovery and leads to long-term consequences like chronic pain, opioid dependency, and reduced quality of life. Althought rodent pain incision models exist, translation to patients is still hampered. To bridge this gap, we combined sensory phenotyping with quantitative proteomics and protein networks in humans and mice after skin incision representing an established model for surgical pain. Initially, we revealed, for the first time, similarities and differences of protein-protein interaction (PPI) networks across both species. Next, we comprehensively phenotyped humans for pain-related symptoms and observed phenotypes with incision-induced proteome changes. Remarkably, post-incision PPI-networks differed between volunteers with small incision-related hyperalgesic areas ("Low responder") versus those with large areas ("High responder"). The latter exhibited a pronounced proteolytic environment associated with persistent inflammation, while an anti-inflammatory protein signature was observed in Low responders. Taken together, we provide unprecedented insights into peripheral processes relevant for developing hyperalgesia and pain after incision. This knowledge will immensely facilitate bidirectional translational pain studies and guide future research on the pathophysiology of pain after surgery and the discovery of novel targets for its treatment and prevention.

neuroscience↗