87: Vertical Climbing in Mice: A Novel Approach for Assessing Pain-Related Impact on Natural Behaviour

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Assessment and Measurement of Pain/Nociception

Background and Aims: For decades, translational failures from preclinical models to patients have stalled analgesic drug discovery. Reasons for the poor translation are multitude, but one reason may be the disconnect between the clinical symptoms that are most bothersome to the patients, and commonly used pain-related outcome measures used in laboratory rodents, like experimenter-evoked responses. Previous studies have explored cage-lid hanging (Zhang 2021) and vertical climbing (Santos 2023) as novel, ethologically valid, and translationally relevant measures to assess the impact of pain on natural behavior in mice. In this project, we sought to investigate vertical climbing as a pain-related measure in various pain-models.

Methods: Vertical climbing setups were build in-house, consisting of a cylindrical metal wire mesh (D: 15cm, H: 25cm) fitted onto a 3D-printed plastic stand/floor. Mice were placed in the cylinder, with the option of resting on the plastic floor, and the amount of voluntary vertical climbing was quantified for 10min using video-recording and EthoVision software. Experiments were conducted across four research groups, using different mouse strains, and focusing on selected pain-types (models): postoperative (plantar incision), inflammatory (intraplantar-CFA), neuropathic (SNI), cancer-induced bone pain (breast cancer, multiple myeloma), arthritis (MIA, CAIA) and migraine (Levcromakalim). Pharmacological validation and reference behaviors were assessed for selected models.

Results: The temporal dynamics and degree of climbing impairment after model-induction generally reflected the expectations from known model-characteristics: mild models, like plantar incision, producing only mild and transient decrease, as opposed to prominent and long-lasting changes in chronic models, like SNI. Across models, sensitive outcome-parameters were: total climbing duration, frequency/duration in the top of the device and distance moved. Each lab successfully implemented the setup and obtained consistent baseline behavior between facilities, although with noticeable differences between strains. Most strains were characterized by consistent high climbing activity-levels, while for others some subjects were excluded at baseline due to poor compliance.

Conclusions: Vertical climbing appears to be an ethologically valid and translationally relevant marker of pain-related impairment of normal activity across models of different types of pain, reflecting the temporal dynamics standardly expected from those models. The setup is easily made using material available in standard hardware stores, further optimized by the addition of a 3D-printed stand and automated tracking software for increased objectivity.

References: Santos, E. J. et al. (2023) Climbing behavior by mice as an endpoint for preclinical assessment of drug effects in the absence and presence of pain. Front. Pain Res. 4 - 2023.

Zhang, H. et al. (2021). Cage-lid hanging behavior as a translationally relevant measure of pain in mice. Pain 162, 1416-1425.

Presenting Author: Sara Hestehave
Submitting Author: Sara Hestehave

Senior Author: Sara Hestehave

IASP 2026 Global Year theme of Neuropathic Pain: No

• Morten Malmberg: DVM - Department of Veterinary and Animal Sciences, University of Copenhagen
• Tobias Bro Bertelsen: DVM - Department of Veterinary and Animal Sciences, University of Copenhagen
• Edward Ciputra: MSc - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
• Pernille Colding-Jørgensen: DVM - Department of Veterinary and Animal Sciences, University of Copenhagen
• Jannie Jutta Jeppesen: BSc - Department of Veterinary and Animal Sciences, University of Copenhagen
• Carolyn Marie Goddard: MSc - Department of Neuroscience, University of Copenhagen
• Kathrine Louise Jensen: PhD - Department of Neuroscience, University of Copenhagen
• Yingyu Tang: MSc - Department of Drug Design and Pharmacology, University of Copenhagen
• Kholud El Masri: BSc - Department of Veterinary and Animal Sciences, University of Copenhagen
• Helene Dragelund Garcia: DVM - Department of Veterinary and Animal Sciences, University of Copenhagen
• Astrid Thostrup Davidsen: BSc - Department of Drug Design and Pharmacology, University of Copenhagen
• Sarah Louise Tangsgaard Christensen: DVM & PhD - Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark
• Karina Obelitz-Ryom: DVM & PhD - Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark
• Chelsea Hopkins: PhD - Department of Drug Design and Pharmacology, University of Copenhagen
• Anne-Marie Heegaard: MD & PhD - Department of Drug Design and Pharmacology, University of Copenhagen
• Kenneth Lindegaard Madsen: PhD - Department of Neuroscience, University of Copenhagen
• Andreas Toft Sørensen: PhD - Department of Neuroscience, University of Copenhagen
• Klas Abelson: PhD - Department of Veterinary and Animal Sciences, University of Copenhagen
• Otto Kalliokoski: PhD - Department of Veterinary and Animal Sciences, University of Copenhagen
• Sara Hestehave: PhD & DVM - Department of Veterinary and Animal Sciences, University of Copenhagen