Neonatal and infant pain assessment

Pain assessment is an essential foundation to mitigate pain and its consequences in the developing child. However, pain assessment in neonates and infants is challenging and, to date, there is no “gold standard” infant pain indicator, measure, or approach. This chapter encompasses (1) a comprehensive evaluation of the most current and well validated neonatal/infant pain assessment measures; (2) an overview on biomarkers and cortical indicators on neonatal/infant pain; (3) the integration of recommendations on pain-assessment measures and practices within clinical practice guidelines, policies, and procedures; and (4) challenges associated with neonatal and infant pain assessment in terms of research, clinical, and knowledge translation issues.

History of pain in children

The problem of pain has always concerned humankind, as pain is a compelling call for attention and a signal to escape. Early efforts to understand pain, and its origins, features, and treatment reflected the duality between spiritual conceptualizations of pain and physiological explanations depending on the predominance of such views in a given culture. When spiritual perspectives dominated, prayer, amulets, supplication, and religious rites controlled approaches to pain treatment. Herbal remedies were often part of such strategies and might themselves been physiologically effective. In ancient writings about pain and disease, treatments for children were often given alongside discussions about the health of women. In this chapter, we trace early approaches to pain in children to the modern era, highlighting points of transition and improvements in pediatric pain management.

Persisting pain in childhood medical illness

Persistent pain in childhood and medical illness can be challenging to manage. The chapter has been revised to give a brief overview of the approach to pain management in some childhood diseases. Better understanding of the etiology of pain mechanisms guide the management of pain. In addition, an understanding of the pathophysiology of the underlying processes and utilizing a stepwise assessment and treatment approach is important. Discussion around the multifaceted approach to childhood pain management incorporating the understanding of the role and place of analgesics in managing these medical illnesses is outline. In addition, appropriate medication or analgesia prescription and the role of nonpharmacological approaches has been considered in this revision.

Pain treatment and prevention in pediatric palliative care

Annually, at least 21 million children could benefit from pediatric palliative care (PPC) and 8 million would need specialized PPC services. In the USA alone, more than 40,000 children aged 0–19 years die annually; 55% of them are infants younger than 1 year of age. Pain is common, under-recognized, and under-treated, especially in children with progressive neurodegenerative and chromosomal conditions with central nervous system impairment. Unrelieved pain is also common in children with advanced serious illness during the end-of-life period, and, when treated, the therapy is commonly ineffective. Treating pain in children with serious illness is not profoundly different than advanced pain management for children with complex acute conditions or diseases such as major trauma, burns, cancer, or those with sickle cell disease in vaso-occlusive crisis. It is important to appreciate that children with serious illness are more likely to simultaneously suffer from acute pain, neuropathic pain, visceral pain, total pain, and chronic pain. As such, multimodal analgesic (i.e., multiple agents, interventions, rehabilitation, psychological modalities, and integrative (“nonpharmacologic,” e.g., behavioral, physiological, and psychological) therapies that act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality must be employed. Opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone, remain the mainstay medications to effectively treat pain in children with serious illness. However, medications alone are often insufficient for optimal pain control. In fact, the paradigm shift away from “medications only” toward offering “multimodal analgesia” to children with serious illness experiencing pain, including addressing chronic pain/primary pain disorders and total pain has become a “game changer” in advancing PPC to ensure that patients can live as long as possible, as well as possible.

Biomarkers of pain in infants and children

Biomarkers are commonly used in clinical care and research as indicators of diseases and physiological states. Preferably, a biomarker should be readily accessible, low in cost, easy to interpret, highly specific, and sensitive to health and disease. Owing to the complexity of the pain system, no unidimensional reliable biomarker for pain has been identified that meets all of these criteria to date. In children, neurologically dependent developmental changes, maturation of physiological stress reactivity systems, and life experience add additional layers of complexity to the use of biomarkers of pain. Nevertheless, readily available and reliable biomarkers reflecting function of the pain system would greatly enhance timely and appropriate understanding and treatment of pain, especially in infants and children with communication, cognitive, and motor disabilities. This chapter examines currently available pain-related biomarkers, their use, and limitations.

Pain and immunity

The central nervous system (CNS) and immune system are inextricably linked. The complexity of their interactions is still being unraveled, but the list of processes mediated wholly or in part by neuroimmune interactions continues to grow. The influence of the immune system is crucial for normal nervous system development both pre- and postnatally, for maintaining neuronal homeostasis in the mature CNS and modulating synaptic plasticity. Aberrations in this crosstalk have been implicated in many neurodevelopmental and psychiatric disorders. It is not feasible to explore neuronal function at any point in the lifespan, in health or disease, without considering the influence of the immune system. In the adult animal it is now well established that pain chronicity is maintained by immune influence upon the neuronal nociceptive system, although, fascinatingly, there is now evidence for a marked sexual dimorphism in how the immune and nervous systems interact. This holds true for pain in early life, where the two still-developing systems provide a very different environment to mediate nociception and pain. Of particular interest is how the immune system and sex interact to early life painful events to prime pain responses in later life.

Pain in the cultural context

Pain and culture are complex and multifactorial phenomena. The concepts are difficult to define and measure since they intersect with the biological, psychological, and social realms. Considering the intrinsic multidimensionality of each phenomenon, we are only beginning to understand the myriad ways in which culture may influence pain. Consequently, (1) the study of the relationship between culture and pain has been fraught with methodological and theoretical challenges; and (2) there is little evidence to support specific guidelines on how to assess and treat pain of specific cultural groups. Therefore, researchers face challenges in conducting research on pain with indigenous populations.

Long-term effects of early pain and injury

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.

Long-term effects of pain in infants

The long-term effects of infant pain are complex, and vary depending on how early in life the exposure occurs, due to differences in developmental maturity of specific systems underway. Changes to later pain sensitivity reflect multiple factors such as age at pain stimulation, extent of tissue damage, type of noxious insult, intensity, and duration. In both full-term and preterm infants exposed to hospitalization, sequelae of early pain are confounded by parental separation and quality of pain treatment. Neonates born very preterm are outside the protective uterine environment, with repeated exposure to pain occurring during fetal life. Especially for infants born in the late second trimester, the cascade of autonomic, hormonal, and inflammatory responses to procedures may induce excitotoxicity with widespread effects on the brain. Quantitative advanced imaging techniques have revealed that neonatal pain in very preterm infants is associated with altered brain development during the neonatal period and beyond. Recent studies now provide evidence of pathways reflecting mechanisms that may underlie the emerging association between cumulative procedural pain exposure and neurodevelopment and behavior in children born very preterm. Owing to immaturity of the central nervous system, repetitive pain in very preterm neonates contributes to alterations in multiple aspects of development. Importantly, there is strong evidence that parental caregiving to reduce pain and stress in preterm infants in the Neonatal Intensive Care Unit (NICU) may prevent adverse effects, and sensitive parenting after NICU discharge may help ameliorate potential long-term effects.

Drugs for neuropathic pain

Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” It is often contrasted with nociceptive pain, which is associated with tissue injury or inflammation. Neuropathic pain conditions in children are qualitatively different from those common in adults and include complex regional pain syndrome, postoperative neuropathic pain, and autoimmune and degenerative neuropathies. Few randomized controlled trials in pediatrics means that evidence from adult studies is extrapolated to guide pharmacological management in children, which is problematic as the etiologies and mechanisms are different. An algorithm for drug therapy is proposed based on the best-available evidence, clinical experience, and the safety of these drugs in pediatric practice. A step-wise approach should be tried methodically according to effectiveness and side effects. Neuropathic pain in children, if identified and treated in a timely manner as part of an interprofessional framework, can be managed effectively.