Pain and placebo in pediatrics: A comprehensive review of laboratory and clinical findings

Abstract

Pain modulation by placebo mechanisms is one of the most robust and best-studied phenomena, yet almost all research investigating the mechanisms and implications of the placebo analgesia are based on adult research. After highlighting crucial aspects that need to be considered in studying pain modulation in children, this comprehensive review examines studies related to pain modulation with an emphasis on factors such as age, neural development and pain measures. Psychological mechanisms underlying placebo effects including: 1) verbally-induced expectations; 2) conditioning and learning mechanisms; 3) child-parent-physician interactions are critically discussed. Taken together, research suggests that placebo mechanisms can impact therapeutic outcomes and potentially be exploited clinically to improve clinical outcomes in pediatric population. Recommendations for further investigating the mechanistic bases and harnessing placebo effects for supportive therapeutic applications are given.

Are Children the Better Placebo Analgesia Responders? An Experimental Approach

“…Evidence from clinical studies suggests that placebo response rates are higher in children compared to adults, supporting anecdotal reports and the common view of higher placebo responses in children 27 . However, placebo response rates in RCTs are also influenced by the natural course of the disease which might be age-dependent.…”

“…A meta-analysis of placebo-controlled trials for the acute or preventive treatment of migraine revealed stronger placebo analgesic effects in children compared to adults 19 . Similar effects have been reported in epilepsy 23 , attention-deficit disorder 34 and major depression 8 (for recent reviews regarding placebo effects in children see 16,27 ). Clinical improvements observed in the placebo groups of clinical trials, also referred to as placebo effects, can be the result of spontaneous remission, regression to the mean, natural course of a disease, biases and true placebo responses.…”

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…Drug actions and placebo effects may interact additively or synergistically in some conditions, such that a treatment is less effective if the placebo component is absent. Therefore, patients’ beliefs and expectancies should be exploited to optimize treatment outcomes (Bingel et al, 2011) in adult as well as pediatric populations (Simmons et al, 2014). …”

A Review of Intravenous Lidocaine Infusion Therapy for Paediatric Acute and Chronic Pain Management

“…Placebo treatments have known effects on endogenous pharmacology, as well as the cognitive and conditioning systems in humans [312][313][314][315][316][317][318][319]. The placebo response rate is higher in children compared with adults [320,321]. Patient expectations and the doctor-patient relationship contribute to placebo analgesia responses and are unique to the individual [322].…”