TY - JOUR

T1 - Effects of Multimodal Therapy, Blinding, and Multi-laboratory Protocol Conduct on the Robustness of the Rat Model of Adjuvant Induced Arthritis

AU - Seveljevic-Jaran, Dasa

AU - Antolic, Maja

AU - Ognjenovic, Anja

AU - Kalliokoski, Otto

AU - Abelson, Klas S.P.

AU - Hau, Jann

N1 - Publisher Copyright: © 2023 International Institute of Anticancer Research. All rights reserved.

PY - 2023

Y1 - 2023

N2 - Background/Aim: The aim of this study was to investigate the effects of multimodal therapy comprising buprenorphine (BUP) and indomethacin (IND) on key translational parameters in the rat adjuvant induced arthritis (AIA) model. Furthermore, we investigated the difference between visual assessment scores and histology scores generated by blinded and non-blinded assessors and the robustness and generalizability of results by conducting a multi-laboratory study. Materials and Methods: The experiment was terminated on day 26 after 11 days (days 15-25) of voluntarily ingested buprenorphine and 7 days of gavage delivered indomethacin treatment (days 19-25). The treatment effects were assessed on the last day of the study, relying on body weight assessment, serum concentrations of α1- acid glycoprotein, and assessment of affected hind paws swelling, in-life and post mortem. Results: Across two laboratories, the combined analgesic treatments had minimal effects on the measured model parameters indicating that multimodal treatment did not affect the translatability of the model. We found an improvement in clinical scores (a negative change in scores) in nearly all medicated animals when scored informed, whereas it was essentially 50:50 for the blinded scorings and no difference between the blinded and informed histological scoring. Conclusion: The present results support the use of more effective analgesic treatment regimens and the good practice recommendations advocating blinding as a mandatory practice in conduct of preclinical in vivo efficacy studies. In spite of minor differences between results obtained at the two sites, there was good agreement between them indicating robustness of the AIA model.

AB - Background/Aim: The aim of this study was to investigate the effects of multimodal therapy comprising buprenorphine (BUP) and indomethacin (IND) on key translational parameters in the rat adjuvant induced arthritis (AIA) model. Furthermore, we investigated the difference between visual assessment scores and histology scores generated by blinded and non-blinded assessors and the robustness and generalizability of results by conducting a multi-laboratory study. Materials and Methods: The experiment was terminated on day 26 after 11 days (days 15-25) of voluntarily ingested buprenorphine and 7 days of gavage delivered indomethacin treatment (days 19-25). The treatment effects were assessed on the last day of the study, relying on body weight assessment, serum concentrations of α1- acid glycoprotein, and assessment of affected hind paws swelling, in-life and post mortem. Results: Across two laboratories, the combined analgesic treatments had minimal effects on the measured model parameters indicating that multimodal treatment did not affect the translatability of the model. We found an improvement in clinical scores (a negative change in scores) in nearly all medicated animals when scored informed, whereas it was essentially 50:50 for the blinded scorings and no difference between the blinded and informed histological scoring. Conclusion: The present results support the use of more effective analgesic treatment regimens and the good practice recommendations advocating blinding as a mandatory practice in conduct of preclinical in vivo efficacy studies. In spite of minor differences between results obtained at the two sites, there was good agreement between them indicating robustness of the AIA model.

KW - adjuvant induced arthritis

KW - blinding

KW - buprenorphine

KW - multi-laboratory study

KW - multimodal therapy

KW - Rat

U2 - 10.21873/invivo.13060

DO - 10.21873/invivo.13060

M3 - Journal article

C2 - 36593032

AN - SCOPUS:85145491912

VL - 37

SP - 115

EP - 123

JO - In Vivo

JF - In Vivo

SN - 0258-851X

IS - 1

ER -