Research has shown that non-pharmacological options, including physical and psychological strategies, may be helpful in treating pain. Children may benefit from cognitive behavioral strategies, such as the use of imagery or relaxation. The application of non-pharmacological techniques has been employed to control pain, stress, and anxiety in children and their parents (9). The present review provides a summary of some of the suggested non-pharmacological strategies aimed at the attenuation or cessation of acute pain in children. In their review of 39 trials with 3,394 participants, Uman et al (15) examined the effects of psychological interventions on needle-related procedural pain and distress in children and adolescents aged 2-19 years. They found strong evidence in support of distraction and hypnosis for needle-related pain and distress in this population (15). Similarly, Accardi and Milling (16) reported the effectiveness of hypnosis in reducing procedure-related pain in children. A systematic literature search on non-pharmacological interventions used for pain management in children in emergency departments was conducted by Wente (9). Among the 14 articles examined, distraction was used in 10 studies, sucrose in two studies, cold application in one study, and parental holding and positioning in one study. Furthermore, decreased pain, distress and anxiety in the parent, child, and/or observer were noted when these procedures were used (9). Cognitive-behavioral strategies should be related to the age and degree of cognitive development of the patient: The oral administration of sucrose and glucose, kangaroo care, tactile stimulation, rocking, singing and soft music, and an environment with soft, fused lights can be effective for infants. For children of school age, the application of cold spray, ice, hot moist packs, massaging and pressure can be useful and satisfying. Furthermore, the use of bandages, dressings and splints are other simple systems that can be used to reduce pain symptoms and anxiety, as these cover the view of the ‘wound’ that is causing psychophysical distress in the child (2). A study involving 98 children and 97 control children/parents examined the beliefs of parents about pain and the efficacy of a parental educational intervention on pain intensity in children and the experience of pain-related unpleasantness at 24 h post-discharge from the emergency department (17). According to the researchers, the active participation of parents in their child's pain management may be more effective than a passive educational intervention (17). Music therapy has also been shown to be a form of distraction that alleviates some types of pain and distress experienced by children undergoing medical procedures in a pediatric emergency department (18). In a previous comprehensive review that included 13 studies and involved 778 patients, the effects of music therapy and opioid treatment on pain anxiety among patients who underwent orthopedic surgery were evaluated. Significant differences were found between the two groups regarding the use of music therapy to reduce pain; however, no statistically significant differences were found in the use of opioids and physiological variables between the two groups. The authors maintained that the timing, duration, and type of music intervention can be modified in relation to specific clinical settings and medical teams (19). A summary of the non-pharmacological techniques used for pain management in children is presented in Table II.

Criticism has been expressed as regards the use of non-pharmacological treatments in the context of acute pediatric pain where pharmacological, physical (splint, ice) and psychological (distraction, breathing) treatments may be more effective. In addition, the literature provides evidence of the difficulties faced by nurses in applying non-pharmacological treatments due to inadequate cooperation from physicians, the heavy workloads of nurses and multiple responsibilities, the low ratio of nurses per patient, and the unfavorable attitudes of nurses to non-pharmacological pain management (20).

Pharmacological therapies are the most commonly used types of treatments for any type of pain. The drugs commonly utilized, as well as the routes of administration, doses and indications on their use are summarized in Table III.

Non-opioid medications. The non-opioid pain medications most commonly used are NSAIDs, which act via their inhibitory actions on cyclooxygenase (COX)-2 enzymes. COX-2 enzymes facilitate the production of pro-inflammatory prostaglandins; thus, prostaglandin production is inhibited to obtain an analgesic effect. Among the most commonly used NSAIDs is ibuprofen. Other COX-2 inhibitors, such as indomethacin, meloxicam and Celebrex, are more frequently used to treat inflammatory and rheumatological disorders than acute pain (20,21A previous randomized controlled trial of acetaminophen, ibuprofen and codeine treatment for acute pain in children with musculoskeletal trauma conducted by Clark et al (21) involved 336 pediatric patients with 100 children in each treatment group. According to the authors of that study, ibuprofen provided the optimal analgesic effect of the three medications studied. In another study, a group of children presenting with uncomplicated extremity fractures was treated in a randomized trial with the oral administration of either morphine or ibuprofen (22). In that trial, 66 children were in the morphine group and 68 in the ibuprofen group. No significant differences in analgesic efficacy were reported between the groups, although morphine was associated with a significantly greater number of adverse effects. The authors of that study maintained that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures (22). In another randomized clinical trial performed by Chang et al (23), of 411 patients with acute extremity pain (mean score, 8.7 on an 11-point numerical rating scale) in an emergency department, no significant differences in pain reduction at 2 h were found. The main pain scores decreased by 4.3 with ibuprofen and acetaminophen, 4.4 with oxycodone and acetaminophen, 3.5 with hydrocodone and acetaminophen, and 3.9 with codeine and acetaminophen. According to the authors of that study, the analgesic effects of NSAIDs were equally efficacious as opioids when treating musculoskeletal pain in adult patients (23).

As is well known, the use of ibuprofen is not recommended for patients with hemorrhagic pathologies, significant dehydration, gastrointestinal disorders and impaired renal function. Jelinek (24) demonstrated that the intravenous administration of ketorolac exhibited an equivalent efficacy in reducing moderate to severe pain as intravenous morphine, although with fewer side-effects. Marzuillo et al (25) reviewed the pharmacokinetics of ketorolac and confirmed its efficacy without severe side-effects, if used for a short period of time. Recently, a pilot single central randomized controlled trial demonstrated that ketorolac had comparable results to morphine when used in children aged 6-17 years with suspected appendicitis (26). The use of ketorolac sublingually as a valid alternative in the absence of intravenous access was also suggested (26). Neri et al (27) demonstrated that sublingual ketorolac and tramadol were equally effective. In cases of suspected bone fractures, studies have shown that sublingual ketorolac and tramadol are effective analgesics for pain management in children aged 4-17 years (25,26).

Paracetamol has been cited in numerous studies as the first-line analgesic agent in emergency departments. Its efficacy is valuable at the correct dose (15 mg/kg) in the treatment of mild to moderate pain. It is characterized by its rapid action and the possibility of different routes of administration (28). A previous meta-analysis revealed that the safety and tolerability profiles of paracetamol and ibuprofen were similar in terms of their efficacy for both pain and fever, and they were rarely associated with severe side-effects (28). In instances of mild or moderate pain, it is preferable to administer paracetamol per os to achieve fairly rapid action and excellent tolerance in the majority of children. By contrast, the rectal route is burdened by slow absorption and unpredictable efficacy both with respect to action time and analgesic capacity (29). In a multicenter emergency department study in 2018, Benini et al (7) found that both paracetamol and ibuprofen were inappropriately used in 83 and 63% of pediatric cases, respectively.

Ketamine, a drug that blocks the effects of glutamate, has been shown to be an effective analgesic in children when administered at sub-dissociative doses (30). Back pain, headache, extremity or musculoskeletal pain, acute abdominal pain and renal colic are controlled by the intravenous administration of ketamine when used appropriately (31,32). In recent years, two systematic reviews and meta-analyses demonstrated that ketamine was non-inferior to opioid medications for acute pain management, as it had a similar analgesic effect and safety profile (33,34).

Opioid medications. Opioid infusion is usually indicated for patients with chronic pain. OF note, a bolus of an intravenous opioid is advised for patients with sudden-onset severe pain or reserved for breakthrough pain for patients who are already receiving opioid infusions. Researchers have recommended that the starting opioid in opioid-naïve patients should be morphine or hydromorphone (30). Typically, immediate-release oral opioids are ordered for pain at intervals of 3-4 h to minimize breakthrough pain and opioid side-effects (30). Additional smaller doses can be administered every 2 h for breakthrough doses. In general, oral use is preferred over intravenous administration, except in cases of poor absorption or an inability to administer drugs enterally (i.e., colitis, mucositis, vomiting). The sublingual route of administration is safe and efficacious both for ketorolac and opioids (34,35). In the trauma setting, intranasal sufentanil or diamorphine administration have both been reported as highly efficacious in the treatment of severe pain (36,37).