Inflammation and nerve injury minimally affect mouse voluntary behaviors proposed as indicators of pain

Abstract

It has been suggested that the lack of rodent behavioral assays that represent the complexities of human pain contributes to the poor translational record of basic pain research findings. Clinically, chronic pain interferes with patient mobility and physical/social activities, and increases anxiety symptoms, in turn negatively impacting quality of life. To determine whether these behaviors are similarly influenced by putative pain manipulations in rodents, we systematically evaluated wheel running, locomotion, gait, social interaction, and anxiety-like behavior in models of inflammation and nerve injury in adult C57BL6/J male mice. We demonstrate that inflammation and nerve injury differentially affect voluntary behaviors while mice are hypersensitive to mechanical stimuli. Bilateral Complete Freund’s Adjuvant (CFA)-induced inflammation transiently suppressed wheel running and locomotion and also induced gait deficits. In contrast, spared nerve injury (SNI) altered gait and impaired gross motor coordination. SNI-induced gait changes were not reversed by the analgesic PD123319, an angiotensin II type 2 receptor antagonist, and are therefore likely to be motor-related rather than pain-related. Neither CFA nor SNI significantly altered social interaction or elicited general anxiety-like behavior. Our findings suggest that in contrast to humans, mobility and physical/social activities are minimally altered, if at all, in mice following inflammation or nerve injury. Keywords: Non-reflexive, Stimulus-independent, Wheel running, Gait, Social interaction, Anxiety