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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.

Research paper by C Z CZ Zhu, A W AW Bannon, S K SK Joshi

Indexed on: 04 Mar '15Published on: 04 Mar '15Published in: European Journal of Pain



Abstract

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.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.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.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.