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Pain processing and management in neonates, especially preterm neonates, differs from older populations. In this review, a brief background on pain processing in neonatal life, pain exposure in Neonatal Intensive Care Units (NICU), the consequences of untreated pain, and the difficulties in treating procedural pain pharmacologically will be presented. A more detailed review of non-pharmacological interventions for procedural pain in neonates will include sensory stimulation approaches, oral sweet solutions, and maternal interventions. Some possible mechanisms for the effectiveness of non-pharmacological interventions are offered. Finally, avenues of research into similar interventions as adjuvant therapies or drug-sparing effects in older populations are suggested. [ABSTRACT FROM AUTHOR]