title: Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: L A
authors.initials: LA
authors.lastname: Bryden
authors.affiliation: 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.
authors.forename: J R
authors.initials: JR
authors.lastname: Nicholson
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Doods
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Pekcec
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity; D010003:Osteoarthritis; D010146:Pain; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D009020:Morphine
keywords: Burrowing; Monosodium iodoacetate; Pain; Rat; Spontaneous behavior