Fig. 8
Neonatal inflammatory pain-induced delayed impairments in social activities and the blocking effects of the anti-inflammatory treatment. Social behavioral tests were carried out to evaluate long-term adverse impacts of the early inflammatory pain on social interactions in juvenile rats. The indomethacin (Indo) treatment was applied to delineate whether inflammation was a crucial mediator in the social behavior changes. a In the three chamber test, male rats, not female rats, in the formalin group, spent less time with the novel stranger and preferred to hide in an empty chamber compared to the control rats. Indomethacin (Indo) co-applied with formalin completely blocked the development of this abnormal behavior. *P < 0.05 vs. control; n = 16 in control and formalin group. n = 5 in indomethacin group. b In the social novelty test, since male rats in the formalin group preferred to stay with a familiar rat, their time with a novel stranger was significantly less than the time spent by controls. The indomethacin (Indo) treatment blocked the social abnormality. *P < 0.05 vs. control; n = 16 in control and formalin group. n = 5 in indomethacin group. c–e In the social interaction test, male rats in the formalin group showed reduced time in social sniffing and social following, although no change was seen with social grooming. Indomethacin (Indo) reversed the behavioral changes. Female rats which received formalin did not show significant deficits in these tests. *P < 0.05 vs. control, # P < 0.05 vs. formalin; n = 16 in control and formalin group. n = 5 in indomethacin group. f A summarized data analysis of all social behavioral tests for male and female rats. The total social time was significantly less with male rats in the formalin group, and the phenotype was prevented by the anti-inflammation treatment. Again, female rats were much more resistant to the formalin insult, showing no social behavior deficits at the juvenile age. *P < 0.05 vs. control, # P < 0.05 vs. formalin; n = 16 in control and formalin group. n = 5 in indomethacin group. ANOVA plus Bonferroni’s analysis was applied to all comparisons in this experiment