Developmental pharmacology of opioids

Recognition of the need for alternative analgesic regimens for managing neonatal and childhood pain has led to a rich literature concerning the ways in which early life pain differs from that at older ages. As in adults, opiates are often considered the gold-standard analgesic class of drugs, of which morphine is the prototypical agent. There is a wealth of data detailing clinical observations, measurements, and interventions with regard to the use of opioids in treating pain in children. Studies in the early part of this century have highlighted that, in humans, age is an important factor that influences the morphine requirement of neonates following surgery, and dose requirements are influenced by both pharmacokinetic and pharmacodynamic factors. Laboratory studies have extended our understanding of changes within the peripheral and central nervous systems that underlie alterations in nociception in early life. This chapter will review what is currently known about the actions of opioids upon nociceptive and nociresponsive elements of the nervous system in early life, how they differ from adult responses, and ask whether manipulating endogenous opioid systems in early life may have consequences on neurodevelopment.

The Role of Affectionate Caregiver Touch in Early Neurodevelopment and Parent–Infant Interactional Synchrony

Though rarely included in studies of parent–infant interactions, affectionate touch plays a unique and vital role in infant development. Previous studies in human and rodent models have established that early and consistent affectionate touch from a caregiver confers wide-ranging and holistic benefits for infant psychosocial and neurophysiological development. We begin with an introduction to the neurophysiological pathways for the positive effects of touch. Then, we provide a brief review of how affectionate touch tunes the development of infant somatosensory, autonomic (stress regulation), and immune systems. Affective touch also plays a foundational role in the establishment of social affiliative bonds and early psychosocial behavior. These touch-related bonding effects are known to be mediated primarily by the oxytocin system, but touch also activates mesocorticolimbic dopamine and endogenous opioid systems which aid the development of social cognitive processes such as social learning and reward processing. We conclude by proposing a unique role for affectionate touch as an essential pathway to establishing and maintaining parent-infant interactional synchrony at behavioral and neural levels. The limitations of the current understanding of affectionate touch in infant development point to fruitful avenues for future research.

Pain

This chapter is dedicated to pain and analgesia, the area where most of the knowledge about the mechanisms of the placebo effect comes from. Expectation of pain reduction plays a crucial role in placebo analgesia. The placebo analgesic effect is mediated by the endogenous opioid systems and antagonized by cholecystokinin (CCK) in some circumstances. In other conditions, the endocannabinoid system is involved. Many brain imaging studies indicate that several areas are involved in placebo analgesia, including the dorsolateral prefrontal cortex and those regions involved in dopaminergic reward mechanisms. The prefrontal lobes are fundamental for a placebo response to occur: if there is no prefrontal control, there is no placebo response. The nocebo hyperalgesic effect is mediated by anxiety, which activates a CCK system that, in turn, facilitates pain transmission. The endogenous pain modulatory descending circuits represent the biological substrate for the action of placebos on pain.

Genesis of the Heroin-Induced Addictive Process: Articulation Between Psychodynamic and Neurobiological Theories

Psychotherapeutic consultations of drug addict's patients in a Care, Support and Prevention Center in Addictology led us to propose several hypotheses on the genesis of addiction and its articulation with currently available neurobiological data. This care center dispenses both pharmacological maintenance medications for heroin dependence, such as methadone or buprenorphine, and psychological support. Our first hypothesis posits that the addictive process is driven by the narcissistic vulnerability of these patients, its neurobiological foundations being mainly mediated by the activation of endogenous opioid systems. Drug use/abuse could be a way to make arise the “True Self,” therefore overcoming the defensive system's set up to protect oneself from early traumas. The neurobiological impact of traumas is also developed and articulated with psychodynamic concepts, particularly those of Winnicott. Additionally, functions of addiction such as defensive, anti-depressant roles and emotional regulation are discussed in relationship with their currently known neuroscientific bases. Although the experience in the psychodynamic clinic is at a level of complexity much higher than what is currently accessible to the neurosciences, most of the research in this domain stays in line with our psychological understanding of the addictive process. Finally, we outline some critically sensitive points regarding the therapeutic support.

The role of caregiver touch in early neurodevelopment and parent-infant interactional synchrony

Though rarely included in studies of parent-infant interactions, affectionate touch plays a unique and vital role in infant development. Previous studies in human and rodent models have established that early and consistent affectionate touch from a caregiver confers wide-ranging and holistic benefits for infant psychosocial and neurophysiological development. We begin by providing a brief review of how affectionate touch tunes the development of infant somatosensory, autonomic (stress regulation) and immune systems. Affective touch also plays a foundational role in the establishment of social affiliative bonds and early psychosocial behavior. These touch-related bonding effects are known to be mediated primarily by the oxytocin system, but touch also activates mesocorticolimbic dopamine and endogenous opioid systems which aid the development of social cognitive processes such as social learning and reward processing. We conclude by proposing a unique role for affectionate touch as an essential pathway to establishing and maintaining parent-infant interactional synchrony at behavioural, physiological and neural levels. The limitations of the current understanding of affectionate touch in infant development point to fruitful avenues for future research.

Developmental pharmacology of opioids

Recognition of the need for alternative analgesic regimens for managing neonatal and childhood pain has led to a rich literature concerning the ways in which early life pain differs from that at older ages. As in adults, opiates are often considered the gold standard analgesic class of drugs, of which morphine is the prototypical agent. There is a wealth of data detailing clinical observations, measurements, and interventions with regard to the use of opioids in treating pain in children. Studies in the early part of this century have highlighted that, in humans, age is an important factor that influences the morphine requirement of neonates following surgery; and dose requirements are influenced by both pharmacokinetic and pharmacodynamic factors. Laboratory studies have extended our understanding of changes within the peripheral and central nervous systems that underlie alterations in nociception in early life. This chapter will review what is currently known about the actions of opioids upon nociceptive and nociresponsive elements of the nervous system in early life, how they differ from adult responses, and ask whether manipulating endogenous opioid systems in early life may have consequences on neurodevelopment.