Experiencing early life maternal separation increases pain sensitivity in adult offspring

Maternal separation is a widely accepted model for studying long-term behavioral changes produced by events during early life and its association with changes in pain sensitivity. Thus, our objective was to evaluate sensitivity to pain, under different stimuli in adult male and female rats that had undergone early life maternal separation. Animals were subjected to maternal separation from postnatal day (PND) 2-15. Maternal behavior and litter weight were evaluated during this period. Sensitivity to pain was assessed in offsprings during adulthood by exposing them to stimuli, including formalin (5%; 20 μl), a hot plate, and the electronic von Frey test, 4, 7, 10, and 24 h after the administration of saline or Freund's complete adjuvant (CFA) injection. Maternal separation did not affect maternal behavior or litter weight during PND 2-15. However, experiencing maternal separation increased pain sensitivity in the rats subjected to formalin by increasing number of flinches and licking time Further, females appeared more sensitive than males to thermal stimuli, as they showed a decrease in latency in the hot plate test. In this test, male and female offsprings that were exposed to early life maternal separation and received the CFA injection also showed a reduction in latency to react to the painful stimuli. In the von Frey test, there was a reduction in withdrawal threshold in maternal separation animals injected with CFA, thus demonstrating a greater sensitivity to the mechanical stimuli. In conclusion, experiencing early life maternal separation increased pain sensitivity in adult offsprings. Thus, our data are important to understand the impact of environmental influences, such as stressful life events during critical developmental periods, on pain vulnerability.