Vertical climbing in mice: a translationally relevant measure of pain-related impact on natural behaviour
- 1University of Copenhagen
Abstract
Despite urgent need for better analgesics, drug development has been complicated by incomplete bench-to-bedside translation. A likely contributing factor is the poor connection between the experimenter-evoked pain-related measures often used in preclinical models, and the clinical symptoms, like broader functional impairment, reported by patients. Here, we asked whether vertical climbing, a species-specific elective behaviour in mice, could serve as a measure of pain-related impairment. We tested male and female mice in a wide range of pain-related models including models of post-operative pain, inflammatory injury, osteoarthritis, rheumatoid arthritis, cancer-induced bone pain, fibrous dysplasia, neuropathic pain, migraine-related pain and facial neuropathy. Vertical climbing was reduced in all models, across five different laboratories, demonstrating the robustness and consistency of this type of behaviour as a novel pain-related outcome measure. Reduced climbing correlated significantly with established pain-related measures, but its time course diverged from that of evoked mechanical allodynia, while aligned more closely with other non-evoked behaviours, like burrowing, home cage activity, wheel running or weight bearing. Pharmacological validation was bidirectional: gabapentin restored climbing in mice with neuropathic injury, and naltrexone reinstated the climbing deficit in mice that had recovered from intraplantar CFA, consistent with persistent pain held in remission by endogenous opioid signalling. Overall, our results indicate that voluntary vertical climbing is a stable, elective behaviour that provides a robust and translationally relevant measure of pain-related functional impairment in mice.
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BibTeX
@misc{malmberg2026vertical,
title = {{Vertical climbing in mice: a translationally relevant measure of pain-related impact on natural behaviour}},
author = {M. E. Malmberg and T. Bro and E. Ciputra and J. J. Jeppesen and C. M. Goddard and I. B. Kanneworff and H. N. Allen and H. D. Garcia and K. L. Jensen and Y. Tang and P. C. Joergensen and K. Walid El Masri and A. Soeberg and A. T. Davidsen and N. K. Grabus and K. Obelitz-Ryom and A. Holm and S. L. T. Christensen and C. Hopkins and A.-M. Heegaard and K. L. Madsen and A. T. Sorensen and R. Khanna and K. S. Abelson and O. Kalliokoski and S. Hestehave},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755655},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755655v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Vertical climbing in mice: a translationally relevant measure of pain-related impact on natural behaviour
AU - M. E. Malmberg
AU - T. Bro
AU - E. Ciputra
AU - J. J. Jeppesen
AU - C. M. Goddard
AU - I. B. Kanneworff
AU - H. N. Allen
AU - H. D. Garcia
AU - K. L. Jensen
AU - Y. Tang
AU - P. C. Joergensen
AU - K. Walid El Masri
AU - A. Soeberg
AU - A. T. Davidsen
AU - N. K. Grabus
AU - K. Obelitz-Ryom
AU - A. Holm
AU - S. L. T. Christensen
AU - C. Hopkins
AU - A.-M. Heegaard
AU - K. L. Madsen
AU - A. T. Sorensen
AU - R. Khanna
AU - K. S. Abelson
AU - O. Kalliokoski
AU - S. Hestehave
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755655
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755655v1
AB - Despite urgent need for better analgesics, drug development has been complicated by incomplete bench-to-bedside translation. A likely contributing factor is the poor connection between the experimenter-evoked pain-related measures often used in preclinical models, and the clinical symptoms, like broader functional impairment, reported by patients. Here, we asked whether vertical climbing, a species-specific elective behaviour in mice, could serve as a measure of pain-related impairment. We tested male and female mice in a wide range of pain-related models including models of post-operative pain, inflammatory injury, osteoarthritis, rheumatoid arthritis, cancer-induced bone pain, fibrous dysplasia, neuropathic pain, migraine-related pain and facial neuropathy. Vertical climbing was reduced in all models, across five different laboratories, demonstrating the robustness and consistency of this type of behaviour as a novel pain-related outcome measure. Reduced climbing correlated significantly with established pain-related measures, but its time course diverged from that of evoked mechanical allodynia, while aligned more closely with other non-evoked behaviours, like burrowing, home cage activity, wheel running or weight bearing. Pharmacological validation was bidirectional: gabapentin restored climbing in mice with neuropathic injury, and naltrexone reinstated the climbing deficit in mice that had recovered from intraplantar CFA, consistent with persistent pain held in remission by endogenous opioid signalling. Overall, our results indicate that voluntary vertical climbing is a stable, elective behaviour that provides a robust and translationally relevant measure of pain-related functional impairment in mice.
ER -