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

Segelcke, D.; Linnemann, J.; Pradier, B.; Kronenberg, D.; Stange, R.; Richter, H.; Goerlich, D.; Baldini, N.; Di Pompo, G.; Verri, W. A.; Avent, S.; Pogatzki-Zahn, E. M.

doi:10.1101/2022.11.19.517016

bioRxiv · 10.1101/2022.11.19.517016

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

Segelcke, D.·Linnemann, J.·Pradier, B.·Kronenberg, D.·Stange, R.·Richter, H.·Goerlich, D.·Baldini, N.·Di Pompo, G.·Verri, W. A.·Avent, S.·Pogatzki-Zahn, E. M.

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Abstract

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.

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Segelcke, D., Linnemann, J., Pradier, B., Kronenberg, D., Stange, R., Richter, H., Goerlich, D., Baldini, N., Di Pompo, G., Verri, W. A., Avent, S., Pogatzki-Zahn, E. M.. 2022-11-22. BEHAVIOURAL VOLUNTARY AND SOCIAL BIOASSAYS ENABLING IDENTIFICATION OF COMPLEX AND SEX DEPENDENT PAIN- (-RELATED) PHENOTYPES IN RATS WITH BONE CANCER. https://doi.org/10.1101/2022.11.19.517016

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