Characterization of behavioral and emotional responses of male and female juvenile rats in the orofacial formalin test following acetaminophen treatment.

Children are frequently affected by acute pain conditions but are underrepresented in clinical trials. Likewise, data on preclinical models of orofacial pain in juvenile rats are scarce. The present study aimed to characterize sensory and emotional responses of male and female juvenile rats in the orofacial formalin test, as well as to investigate the effect of acetaminophen, due to its wide use in the pediatric population. Male and female Wistar rats (21-35 days) were treated with acetaminophen (100 mg/kg or 300 mg/kg), or vehicle systemically followed by injection of 2.5 % formalin or saline into the right upper lip. Behavior was recorded for 30 min, concomitantly with the caption of ultrasonic vocalization (USV) emission, and followed by testing in the open field. Formalin induced a biphasic nociceptive response in male and female rats, but acetaminophen did not change the grooming time in any of the phases. USV analysis did not reveal a significant influence of the pain condition nor the treatments in aversive or appetitive calls emission. Formalin caused a reduction in locomotion in male rats, as well as acetaminophen per se. In females, locomotion was impaired only in formalin-injected rats that received acetaminophen. Altogether, these results suggest that the formalin test may be used for the analysis of the nociceptive behavior in male and female juvenile rats, but USV analysis did not reflect the emotional component of pain in this context. Moreover, further studies that explore the efficacy and safety of acetaminophen in the pediatric population are clearly warranted.