98 Pain threshold may be altered in children long after early surgery, especially in regions of prior tissue damage, which is important if another surgery is needed later. However, the direction and magnitude appear

to depend on many factors that are unclear at this point, perhaps at least in part due to inclusion of children born preterm and full-term. It is unknown whether physiological immaturity at the time of surgery may Inhibitors,research,lifescience,medical contribute to the long-term impact on later touch or pain threshold. Although repeated procedural pain early in life in infants born preterm is associated with altered sensory thresholds when tested in experimental conditions, studies of self-report, however, suggest no differences in “everyday” pain or pain syndromes compared to full-term controls in adolescents or young adults born preterm.63,92,94,95,99,100 Furthermore, in a prospective cohort study of self-completed questionnaires in 18,572 participants at age 45 years, there was no significant association between adults

born Inhibitors,research,lifescience,medical at low birth-weight or very low birth-weight and reports of chronic pain, with or without adjustment for medical and social confounders.101 Thus, although there is evidence that touch and pain thresholds differ, as well as altered brain activity in Epacadostat concentration response to pain in Inhibitors,research,lifescience,medical children born preterm, the literature is consistent that there is no evidence for increased prevalence of pain syndromes in adulthood. PARENTING AND PAIN IN PRETERM INFANTS In a longitudinal randomized trial where mothers were taught how to reduce stress in their low-birth-weight

infants, IQ scores at 9 years of age were >10 points higher in the Inhibitors,research,lifescience,medical intervention group.102,103 In another trial, preterm infants exposed to a parental intervention similar to that used in the randomized trials cited above102,103 demonstrated enhanced brain maturation and connectivity on MRI at term-equivalent age.48 In a cohort study, we found that greater positive maternal Inhibitors,research,lifescience,medical interaction buffered the relationship of neonatal procedural pain exposure with poorer focused attention in very preterm infants at 8 months’ CA and was protective against internalizing (anxiety/depressive) behaviors at 18 months’ CA. Yet, it remains unknown whether the relation between mafosfamide adverse brain development and impaired cognitive outcome is improved by supportive parent–child interactions. Potentially protective factors in the face of early biological adversity are recognized as a crucial focus to explain the wide variability of neurodevelopmental outcomes in very preterm infants.104 Importantly, there is converging evidence that preterm infants are more developmentally vulnerable to their parent interaction.82,83,104 These data indicate that parents’ behaviors play a key role in their child’s neurodevelopment and may compensate for adverse clinical exposure and compromised early brain development. Maternal care of rat pups positively affects adult sensitivity to pain following neonatal inflammation.