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Arthritis Res Ther. 2016 Jun 23;18:150. doi: 10.1186/s13075-016-1047-5.

Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model.

Author information

1
Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.
2
Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada.
3
Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
4
CiToxLAB North America Inc., Laval, Quebec, Canada.
5
Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada. eric.troncy@umontreal.ca.
6
Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada. eric.troncy@umontreal.ca.

Abstract

BACKGROUND:

Lack of validity in osteoarthritis pain models and assessment methods is suspected. Our goal was to 1) assess the repeatability and reproducibility of measurement and the influence of environment, and acclimatization, to different pain assessment outcomes in normal rats, and 2) test the concurrent validity of the most reliable methods in relation to the expression of different spinal neuropeptides in a chemical model of osteoarthritic pain.

METHODS:

Repeatability and inter-rater reliability of reflexive nociceptive mechanical thresholds, spontaneous static weight-bearing, treadmill, rotarod, and operant place escape/avoidance paradigm (PEAP) were assessed by the intraclass correlation coefficient (ICC). The most reliable acclimatization protocol was determined by comparing coefficients of variation. In a pilot comparative study, the sensitivity and responsiveness to treatment of the most reliable methods were tested in the monosodium iodoacetate (MIA) model over 21 days. Two MIA (2 mg) groups (including one lidocaine treatment group) and one sham group (0.9 % saline) received an intra-articular (50 μL) injection.

RESULTS:

No effect of environment (observer, inverted circadian cycle, or exercise) was observed; all tested methods except mechanical sensitivity (ICC <0.3), offered good repeatability (ICC ≥0.7). The most reliable acclimatization protocol included five assessments over two weeks. MIA-related osteoarthritic change in pain was demonstrated with static weight-bearing, punctate tactile allodynia evaluation, treadmill exercise and operant PEAP, the latter being the most responsive to analgesic intra-articular lidocaine. Substance P and calcitonin gene-related peptide were higher in MIA groups compared to naive (adjusted P (adj-P) = 0.016) or sham-treated (adj-P = 0.029) rats. Repeated post-MIA lidocaine injection resulted in 34 times lower downregulation for spinal substance P compared to MIA alone (adj-P = 0.029), with a concomitant increase of 17 % in time spent on the PEAP dark side (indicative of increased comfort).

CONCLUSION:

This study of normal rats and rats with pain established the most reliable and sensitive pain assessment methods and an optimized acclimatization protocol. Operant PEAP testing was more responsive to lidocaine analgesia than other tests used, while neuropeptide spinal concentration is an objective quantification method attractive to support and validate different centralized pain functional assessment methods.

KEYWORDS:

Acclimatization; Animal preclinical model; Methods; Monosodium iodoacetate; Neuropeptide; Osteoarthritis; Pain metrology; Validation

PMID:
27338815
PMCID:
PMC4918125
DOI:
10.1186/s13075-016-1047-5
[Indexed for MEDLINE]
Free PMC Article

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