The novel compound AS1 abolishes second phase formalin nocifensive behavior

Abstract

In larval zebrafish Analgesic Screen One (AS1), is a small molecule analgesic that reverses the valence of noxious stimuli rendering these aversive stimuli attractive. In this study, we evaluated the analgesic potential of AS1 in mice by measuring the effects of this compound on behavioral models of pain, locomotion and valence. We found that AS1 selectively abolished second phase nocifensive behavior elicited by the chemical irritant formalin, while having no effect on acute or inflammatory withdrawal thresholds evoked by thermal or mechanical stimuli. Unlike in larval zebrafish, AS1 did not induce attraction to aversive thermal stimuli. Neuronal activity profiling with the immediate-early gene c-Fos revealed that AS1 did not alter formalin evoked activity in the dorsal horn of spinal cord, but instead elevated activity in numerous brain regions associated with pain processing, analogous to findings in zebrafish. Further behavioral testing suggested that AS1 is not intrinsically aversive or appetitive but does promote reduced spontaneous locomotion and anxiogenic behavior. Collectively, these data suggest that AS1 may have select analgesic properties in mice.