Complete Freund's adjuvant-induced reduction of exploratory activity in a novel environment as an objective nociceptive endpoint for sub-acute inflammatory pain model in rats.
BACKGROUND
Hind paw injection of complete Freund's adjuvant (CFA) is a commonly used sub-acute inflammatory pain model in rodents with typical subjective endpoint measurements of paw withdrawal to thermal or mechanical stimuli.


METHODS
Here, we assessed CFA-induced reduction of exploratory activity in a novel environment (CRANE) as an objective nociceptive endpoint in rats. CFA (50%) was subcutaneously injected into the plantar aspect of the hind paw either unilaterally or bilaterally (150 μL/paw). Exploratory activity was recorded using an automated locomotor activity system.


RESULTS
Bilateral CFA injection reduced exploratory activity 4-48 h following injection, compared to sham controls. Unilateral CFA injection produced less reduction of exploratory activity, compared to bilateral injection. Effects of orally dosed standard analgesics on CRANE were examined 48 h following bilateral CFA injection. Diclofenac treatment produced dose-related reversal of CRANE at 0.03-1.0 mg/kg with a plateau effect observed at higher doses (up to 30 mg/kg). Ibuprofen also produced dose-related reversal CRANE at 0.3-3.0 mg/kg with a plateau effect at higher doses (up to 60 mg/kg). Similarly, celecoxib produced dose-related reversal CRANE at 3-10 mg/kg, but not 30 mg/kg. Gabapentin (up to 100 mg/kg) and duloxetine (up to 30 mg/kg) produced no reversal of CRANE.


CONCLUSIONS
The results presented here demonstrate that CRANE provides an objective assessment of pain behaviours for sub-acute inflammatory pain in rats. The pharmacological profile of standard analgesics supports that CRANE model may potentially be used to identify novel analgesic agents for the treatment of sub-acute inflammatory pain.
Neuroscience Research, Research and Development, AbbVie, North Chicago.
C Z
CZ
Zhu
Neuroscience Research, Research and Development, AbbVie, North Chicago.
A W
AW
Bannon
Neuroscience Research, Research and Development, AbbVie, North Chicago.
S K
SK
Joshi
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D000068579:Celecoxib / Q000008:administration & dosage / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D004008:Diclofenac; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005620:Freund's Adjuvant; D000068736:Duloxetine Hydrochloride; D000068579:Celecoxib; D007052:Ibuprofen