Acknowledgements This Europain project has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking (under grant agreement number 115007), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in-kind contribution (see http://www.imieuropain.org/ for details). Eli Lilly and Company United Kingdom: We would like to thank Dr Gary Gilmour for his assistance in bringing forward this publication. Karolinska Institute: A. Delaney also received funding from Ulla & Gustaf af Ugglas Foundation; EU Project FP7-Health-2013-Innovation-1602919-2. Boehringer Ingelheim: We would like to thank Stacey Gould for technical assistance.Peer reviewedPublisher PD

Abdel-Sattar

Andrews

Baker

Bath

Beery

Benoliel

Bryden

Caspani

Ciaramitaro

Crossley

Currie

Deacon

DeLeo

Dermanovic Dobrota

Finnerup

Freitas

Gould

Grace

Gupta

Hasnie

Holman

Huang

Jirkof

Kandasamy

Kerins

Kilkenny

Kramer

Landis

Lemons

Lewejohann

Macleod

Maier

Mandillo

Miletic

Naji-Esfahani

Negus

Okun

Parent

Percie du Sert

Pereira

Peters

Pfau

Phillips

Prinz

Rakel

Rice

Richter

Roeska

Rutten

Schaap

Seretny

Sindrup

Sorge

Spruijt

Thut

Turner

Wallace

Whittaker

Woolf

Zimmermann

Pain

PubMed

Rachel Wodarski

Ada Delaney

Camilla Ultenius

Rosie Morland

Nick Andrews

Catherine Baastrup

Luke A. Bryden

Ombretta Caspani

Thomas Christoph

Natalie J. Gardiner

Wenlong Huang

Jeffrey D. Kennedy

Suguru Koyama

Dominic Li

Marcin Ligocki

Annika Lindsten

Ian Machin

Anton Pekcec

Angela Robens

Sanziana M. Rotariu

Sabrina Voß

Marta Segerdahl

Carina Stenfors

Camilla I. Svensson

Rolf-Detlef Treede

Katsuhiro Uto

Kazumi Yamamoto

Kris Rutten

Andrew S.C. Rice

Crossref

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the futur

Wodarski, Rachel

Delaney, Ada

Ultenius, Camilla

Morland, Rosie

Andrews, Nick

Baastrup, Catherine

Bryden, Luke

Caspani, Ombretta

Christoph, Thomas

Gardiner, Natalie

Huang, Wenlong

Kennedy, Jeffrey D.

Koyama, Suguru

Li, Dominic

Ligocki, Marcin

Lindsten, Annika

Machin, Ian

Pekcec, Anton

Robens, Angela

Rotariu, Sanziana M.

Voss, Sabrina

Segerdahl, Marta

Stenfors, Carina

Svensson, Camilla I.

Treede, Rolf-Detlef

Uto, Katsuhiro

Yamamoto, Kazumi

Rutten, Kris

Rice, Andrew S.C.

The University of Manchester - Institutional Repository

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future

Wodarski, R

Delaney, A

Ultenius, C

Morland, R

Andrews, N

Baastrup, C

Bryden, LA

Caspani, O

Christoph, T

Gardiner, NJ

Huang, W

Kennedy, JD

Koyama, S

Li, D

Ligocki, M

Lindsten, A

Machin, I

Pekcec, A

Robens, A

Rotariu, SM

Vo, S

Segerdahl, M

Stenfors, C

Svensson, CI

Treede, RD

Uto, K

Yamamoto, K

Rutten, K

Rice, AS

Spiral - Imperial College Digital Repository

English

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

Acknowledgements This Europain project has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking (under grant agreement number 115007), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in-kind contribution (see http://www.imieuropain.org/ for details). Eli Lilly and Company United Kingdom: We would like to thank Dr Gary Gilmour for his assistance in bringing forward this publication. Karolinska Institute: A. Delaney also received funding from Ulla & Gustaf af Ugglas Foundation; EU Project FP7-Health-2013-Innovation-1602919-2. Boehringer Ingelheim: We would like to thank Stacey Gould for technical assistance.Peer reviewe

Bryden, Luke A.

Gardiner, Natalie J.

Voß, Sabrina

Rice, Andrew S. C.

Aberdeen University Research

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat : a prospective multicentre study

http://dx.doi.org/10.1097/j.pain.0000000000000657

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat : a prospective multicentre study

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Crossref

The University of Manchester - Institutional Repository

Spiral - Imperial College Digital Repository

Aberdeen University Research