TY - JOUR
T1 - Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study
AU - Wodarski, Rachel
AU - Delaney, Ada
AU - Ultenius, Camilla
AU - Morland, Rosie
AU - Andrews, Nick
AU - Baastrup, Catherine
AU - Bryden, Luke
AU - Caspani, Ombretta
AU - Christoph, Thomas
AU - Gardiner, Natalie
AU - Huang, Wenlong
AU - Kennedy, Jeffrey D.
AU - Koyama, Suguru
AU - Li, Dominic
AU - Ligocki, Marcin
AU - Lindsten, Annika
AU - Machin, Ian
AU - Pekcec, Anton
AU - Robens, Angela
AU - Rotariu, Sanziana M.
AU - Voss, Sabrina
AU - Segerdahl, Marta
AU - Stenfors, Carina
AU - Svensson, Camilla I.
AU - Treede, Rolf-Detlef
AU - Uto, Katsuhiro
AU - Yamamoto, Kazumi
AU - Rutten, Kris
AU - Rice, Andrew S.C.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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
AB - 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
U2 - 10.1097/j.pain.0000000000000657
DO - 10.1097/j.pain.0000000000000657
M3 - Article
SN - 0304-3959
VL - 157
SP - 2350
EP - 2365
JO - Pain
JF - Pain
IS - 10
ER -