Long-Term Effects of Stressors during the Neonatal Period of Development on the Nociceptive System and Psychoemotional Behavior
The long-term effects of peripheral inflammatory pain, transient maternal separation stress, and the combination of these factors on days 1 and 2 of life or on days 7 and 8 of life were studied in relation to measures of baseline pain (in the absence of an inflammatory process), prolonged responses to reinitiation of inflammation in the formalin test, levels of anxiety, extents of depressive behavior, and spatial learning ability when the animals reached adult age (90 days). In adult rats, study parameters showed changes depending on the type of early treatment and the age at which it was applied: inflammatory pain induced hypoalgesia in the hotplate test and degraded spatial learning ability in the Morris maze; maternal separation stress on days 1–2 but not days 7–8 increased pain responses in the formalin test. Regardless of the age at which the rat pups were subjected to treatments, repeated induction of inflammatory foci induced increased pain responses when animals reached adulthood. In the forced swimming test, immobility was increased in rats subjected to any of the treatments. The effects of combined pain and stress did not increase the influences of each applied alone. These new data contribute to the further development of our understanding of the longterm influences of harmful pain and stressors and their interactions in the neonatal period of development on the functional activity of the tonic nociception system and psychoemotional behavior.
Keywordsrepeated pain stress neonatal period adaptive behavior adult rats
Unable to display preview. Download preview PDF.
- 1.I. P. Butkevich, V. A. Mikhailenko, Yu. A. Lavrova, and N. A. Ulanova, “Repeated pain syndrome in inflammation in neonatal males alters adaptive behavior in the adolescent period of development,” Ros. Fiziol. Zh., 100, No. 11, 1241–1251 (2014).Google Scholar
- 2.V. A. Mikhailenko, I. P. Butkevich, E. A. Vershinina, and N. A. Ulanova, “Duration of changes in adaptive behavior after pain in inflammation during the neonatal period,” Zh. Evolyuts. Biokhim. Fiziol., 51, No. 2, 108–114 (2015).Google Scholar
- 8.R. E. Grunau, “Neonatal pain in very preterm infants: long-term effects on brain, neurodevelopment and pain reactivity,” Rambam Maimonides Med. J., 4, No. 4, e0025, doi: 10.5041/RMMJ.10132.2013.Google Scholar
- 15.M. Rincén-Cortés and R. M. Sullivan, “Early life trauma and attachment: immediate and enduring effects on neurobehavioral and stress axis development,” Front. Endocrinol., 5, 33 (2014).Google Scholar
- 19.N. C. Victoria, and A. Z. Murphy, “The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence,” Dev. Neurobiol., 37, 1–13 (2016).Google Scholar
- 21.S. M. Walker, S. Beggs, and M. L. Baccei, “Persistent changes in peripheral and spinal nociceptive processing after early tissue injury,” Exp. Neurology, pii: S0014-4886 (15)30030-3 (2015), doi: 10.1016/j.expneurol.Google Scholar