L A Bryden1, J R Nicholson2, H Doods3, A Pekcec4. 1. Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: luke.bryden@student.manchester.ac.uk. 2. Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: janet.nicholson@boehringer-ingelheim.com. 3. Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: henri.doods@boehringer-ingelheim.com. 4. Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: anton.pekcec@boehringer-ingelheim.com.
Abstract
OBJECTIVE: To characterize deficits in burrowing behavior - an ethologically-relevant rodent behavior - in the monosodium iodoacetate (MIA) rat model of osteoarthritis (OA), and the sensitivity of these deficits to reversal by analgesic drugs of both prototypical and novel mechanisms of action. A second objective was to compare the burrowing assay to a spontaneous locomotor activity (sLA) assay. METHOD: Male Wistar Han rats (200-220 g) received intrarticular (i.a.) injections of MIA or saline for sham animals. A deficit in the amount of sand burrowed from steel tubes filled with 2.5 kg of sand was used as a measure of pain-related behavior, and sensitivity to reversal of these deficits by analgesic drugs was assessed in bilaterally MIA-injected rats. RESULTS: Bilateral MIA injections induced a significant impairment of burrowing behavior, which was concentration-dependent. The temporal pattern of the deficits was biphasic: a large deficit at 3 days post-injection, resolving by day 14 and returning at the 21 and 28 day time points. At the 3 day time point ibuprofen, celecoxib and an anti-nerve growth factor (NGF) monoclonal antibody (mAb) were able to significantly reinstate burrowing behavior, whereas the fatty acid amide hydrolase (FAAH) inhibitor PF-04457845 and morphine displayed no reversal effect. Morphine impaired burrowing behavior at 3 mg/kg in sham animals. Deficits in rearing frequency in the locomotor activity assay proved irreversible by analgesics. CONCLUSION: Burrowing behavior provides an objective, non-reflexive read-out for pain-related behavior in the MIA model that has predictive validity in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and an anti-NGF mAb.
OBJECTIVE: To characterize deficits in burrowing behavior - an ethologically-relevant rodent behavior - in the monosodium iodoacetate (MIA) rat model of osteoarthritis (OA), and the sensitivity of these deficits to reversal by analgesic drugs of both prototypical and novel mechanisms of action. A second objective was to compare the burrowing assay to a spontaneous locomotor activity (sLA) assay. METHOD: Male Wistar Han rats (200-220 g) received intrarticular (i.a.) injections of MIA or saline for sham animals. A deficit in the amount of sand burrowed from steel tubes filled with 2.5 kg of sand was used as a measure of pain-related behavior, and sensitivity to reversal of these deficits by analgesic drugs was assessed in bilaterally MIA-injected rats. RESULTS: Bilateral MIA injections induced a significant impairment of burrowing behavior, which was concentration-dependent. The temporal pattern of the deficits was biphasic: a large deficit at 3 days post-injection, resolving by day 14 and returning at the 21 and 28 day time points. At the 3 day time point ibuprofen, celecoxib and an anti-nerve growth factor (NGF) monoclonal antibody (mAb) were able to significantly reinstate burrowing behavior, whereas the fatty acid amide hydrolase (FAAH) inhibitor PF-04457845 and morphine displayed no reversal effect. Morphine impaired burrowing behavior at 3 mg/kg in sham animals. Deficits in rearing frequency in the locomotor activity assay proved irreversible by analgesics. CONCLUSION: Burrowing behavior provides an objective, non-reflexive read-out for pain-related behavior in the MIA model that has predictive validity in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and an anti-NGF mAb.
Authors: Sonny Hermanus Johannes Sliepen; Marta Diaz-Delcastillo; Johanna Korioth; Rikke Brix Olsen; Camilla Kristine Appel; Thomas Christoph; Anne-Marie Heegaard; Kris Rutten Journal: In Vivo Date: 2019 Jul-Aug Impact factor: 2.155
Authors: Grazielle C Aguiar; Celso M Queiroz-Junior; Giovana L Sitta; Flávio A Amaral; Mauro M Teixeira; Marcelo V Caliari; Anderson J Ferreira Journal: Int J Exp Pathol Date: 2016-12 Impact factor: 1.925