Pharmacologic Management of Pain in Children: Balancing Evidence, Safety, and Clinical Challenges

Abstract

Highlights What are the main findings? Pediatric pain pharmacotherapy requires a mechanism-based and developmentally informed approach. Evidence is strongest for acute nociceptive pain, whereas treatment of neuropathic and particularly nociplastic pain remains limited by scarce pediatric-specific trials and frequent off-label use. What are the implications of the main findings? Treatment selection should integrate pain mechanisms, acute versus chronic presentation, age, developmental pharmacology, indication, and drug-specific safety. In chronic pediatric pain, functional recovery rather than complete pain elimination should represent the primary therapeutic goal, with pharmacotherapy integrated into multidisciplinary management. Abstract Pain in children remains frequently underrecognized and undertreated despite significant advances in pediatric analgesia. The pharmacologic management of pediatric pain is challenging due to developmental differences in pharmacokinetics and pharmacodynamics, variability in drug metabolism, age-dependent responses, and the limited availability of high-quality pediatric clinical trials. This narrative review summarizes current evidence regarding the pharmacologic management of nociceptive, neuropathic, and nociplastic pain in children, integrating developmental pharmacology, efficacy data, safety considerations, and limitations of available evidence. A mechanism-based classification of pain provides a useful framework for therapeutic decision-making; however, clinical conditions often involve overlapping mechanisms requiring individualized and multidisciplinary approaches. Evidence supporting pharmacological interventions varies considerably according to pain type. Acetaminophen and NSAIDs remain the most used agents for nociceptive pain, while opioids retain a role in selected cases of moderate-to-severe pain under careful monitoring. Management of neuropathic and nociplastic pain remains particularly challenging due to limited pediatric trials, frequent off-label prescribing, and reliance on extrapolation from adult populations. Future research should focus on age-specific randomized controlled trials, pharmacokinetic and pharmacogenomic variability, long-term safety outcomes, and integration of pharmacologic treatments within multimodal pain management strategies.