title: Pharmacological characterization of intraplantar Complete Freund's Adjuvant-induced burrowing deficits.
abstract: BACKGROUND
  It has recently been suggested that non-reflex behavioral readouts, such as burrowing, may be used to evaluate the efficacy of analgesics in rodent models of pain.
  
  
  OBJECTIVE
  To confirm whether intraplantar Complete Freund's Adjuvant (CFA)-induced pain reliably results in burrowing deficits which can be ameliorated by clinically efficacious analgesics as previously suggested.
  
  
  METHODS
  Uni- or bilateral intraplantar CFA injections were performed in male Wistar Han rats. The time- and concentration-response of burrowing deficits and the ability of various analgesics to reinstate burrowing performance were studied. An anxiolytic was also tested to evaluate the motivational cue that drives this behavior.
  
  
  RESULTS
  Burrowing deficits were dependent on the concentration of CFA injected, most pronounced 24h after CFA injections and even more pronounced after bilateral compared with unilateral injections. Celecoxib and ibuprofen reversed CFA-induced burrowing deficits whereas indomethacin failed to significantly reinstate burrowing performance. Morphine and tramadol failed to reinstate burrowing performance, but sedation was observed in control rats at doses thought to be efficacious. An antibody directed against the nerve growth factor significantly improved CFA-induced burrowing deficits. Neither gabapentin nor the anxiolytic diazepam reinstated burrowing performance and the opportunity to find shelter did not modify burrowing performance.
  
  
  CONCLUSIONS
  Burrowing is an innate behavior reliably exhibited by rats. It is suppressed in a model of inflammatory pain and differently reinstated by clinically efficacious analgesics that lack motor impairing side effects, but not an anxiolytic, suggesting that this assay is suitable for the assessment of analgesic efficacy of novel drugs.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Stacey Anne
authors.initials: SA
authors.lastname: Gould
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Germany, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Henri
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.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lamla
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: Anton
authors.initials: A
authors.lastname: Pekcec
mesh_terms: D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D000068579:Celecoxib / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant; D000077206:Gabapentin; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000276:immunology; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D017208:Rats, Wistar; D014147:Tramadol / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000700:Analgesics; D000906:Antibodies; D003509:Cyclohexanecarboxylic Acids; D014147:Tramadol; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor; D000068579:Celecoxib; D003975:Diazepam; D007052:Ibuprofen; D007213:Indomethacin
keywords: Analgesic; Anti-NGF; Burrowing; CFA; Inflammation; Spontaneous pain