Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar–Kyoto rats

Abstract

IntroductionChronic pain is often associated with comorbid anxiety and cognitive dysfunction, negatively affecting therapeutic outcomes. The influence of genetic background on such interactions is poorly understood. The stress-hyperresponsive Wistar–Kyoto (WKY) rat strain, which models aspects of anxiety and depression, displays enhanced sensitivity to noxious stimuli and impaired cognitive function, compared with Sprague–Dawley (SD) counterparts. However, pain- and anxiety-related behaviors and cognitive impairment following induction of a persistent inflammatory state have not been investigated simultaneously in the WKY rats. Here we compared the effects of complete Freund's adjuvant (CFA)-induced persistent inflammation on pain-, negative affect- and cognition-related behaviors in WKY vs. SD rats.MethodsMale WKY and SD rats received intra-plantar injection of CFA or needle insertion (control) and, over the subsequent 4 weeks, underwent behavioral tests to assess mechanical and heat hypersensitivity, the aversive component of pain, and anxiety- and cognition-related behaviors.ResultsThe CFA-injected WKY rats exhibited greater mechanical but similar heat hypersensitivity compared to SD counterparts. Neither strain displayed CFA-induced pain avoidance or anxiety-related behavior. No CFA-induced impairment was observed in social interaction or spatial memory in WKY or SD rats in the three-chamber sociability and T-maze tests, respectively, although strain differences were apparent. Reduced novel object exploration time was observed in CFA-injected SD, but not WKY, rats. However, CFA injection did not affect object recognition memory in either strain.ConclusionsThese data indicate exacerbated baseline and CFA-induced mechanical hypersensitivity, and impairments in novel object exploration, and social and spatial memory in WKY vs. SD rats.

Examining Cognitive Performance in Mice using the Open-Source Operant Feeding Device FED3

“…Morris Water Maze 19,20 , Barnes Maze 16 ) and recognition tasks (e.g. novel object recognition [21][22][23] ) have been implemented to measure cognitive function in large cohorts of mice 12,[24][25][26][27][28] , including chemically-induced rodent pain models such as Chemotherapy Induced Peripheral Neuropathy [29][30][31] and Complete Freund's Adjuvant 32 which exhibit a limited period of pain sensitivity. However, these paradigms rely on hippocampalbased spatial memory and the HPA-driven stress-influenced motivated behavior that provide an experimental challenge for evaluating executive function and other subdomains of cognitive behavior.…”