Pediatric Pain Management with Opioids

Dear Colleagues,

Opioids^[1] are the oldest class of drugs known to medicine; after nearly six millennia, they are still frequently prescribed by clinicians. Known to the Sumerians, who cultivated the poppy plant in Mesopotamia as early as 3400 BCE, opioids were later prescribed by Hippocrates (460–357 BCE) for analgesic effects, and Greeks, and later Romans, as a sedative. In 330 BCE Alexander the Great introduced opium to India, and it was well known in ancient China thousands of years before that.

Over time, the opioid molecule has been chemically modified to increase its potency and to engineer its pharmacokinetics (PK) and pharmacodynamics (PD), yet its fundamental mechanism of action, biology, effects and side effects remain the same as in Mesopotamia at the dawn of history. Why then have opioids, in spite of their side effects, toxicity, and potential for addiction, persisted in medical therapeutics for six thousand years?  Simply because opioids remain the single most potent and effective analgesic for pain, and their persistence as therapeutic substances throughout human history is testament to their benefit.

In the last century, the non-therapeutic, recreational use of opioids was criminalized in the West, but recently the therapeutic use of opioids has come under fire by governments in response to the news that opioid deaths are becoming more common, or at least, more commonly recognized by the press and the political class. The U.S. Centers for Disease Control (CDC) has labelled this “the opioid epidemic,” using a powerful and fear-inspiring word (“epidemic: rampant, widespread, wide-ranging, extensive, pervasive). Yet in spite of this dire pronouncement, there is not convincing evidence that opioid use is epidemic, or that medical use of opioids has driven the increasing number of opioid related deaths.

The chemistry, pharmacology, and molecular biology of opioids, and their therapeutic and non-therapeutic effects have been exhaustively investigated in adult humans, but hardly so in newborns, infants, children or adolescents. Consequently, of the dozens of opioids and opioid formulations on the market today there is only one that has been approved and labelled for use in children of two years of age and older by the U.S. Food and Drug Administration (FDA), transdermal fentanyl.  This presents clinicians who treat children in pain with a quandary. Clinicians are ethically obligated to alleviate suffering and treat pain in their patients, and they know that the most effective method at their disposal is frequently the administration of opioids, yet these drugs are not “approved” by regulatory bodies to be used in their patients. Further, too little science exists to guide their therapeutic decisions, and the government is now subjecting clinicians to increased scrutiny and criticism of their opioid prescribing.

This journal edition is dedicated to opioid pharmacology and therapeutics in pediatrics. In the following pages you will read of the current state of pediatric pharmacological knowledge of opioids, their conventional, experimental, rational, and irrational use in pediatric pain conditions and syndromes, of their use in ages from the premature infant to the adolescent, and of the different routes of opioid administration, from oral to neuraxial. This Special Issue will describe opiooid toxicology and the management of adverse effects, and very importantly given the current dialog in the lay press, their potential for misuse and addiction in the pediatric population, including whether there is a relationship between opioid addiction in adults and prior opioid exposure in childhood. Finally we will shine a light on the future of opioid use in children, discussing the role that may be played by academia, the pharmaceutical industry, and its regulators in developing analgesics for children.

Dr. Elliot J. Krane
Guest Editor

^[1] Throughout this issue we will not use the word “narcotic,” which not only has pejorative and legal connotations, but is a misnomer (these drugs do much more than induce “narcosis,” “numbed state” in Greek). “Opiate” refers to substances chemically derived from opium. “Opioid” refers to molecules that are similar to the opium molecule in structure or mechanism of action. Morphine is both an opiate and an opioid, but fentanyl is only an opioid. We will use the term opioid to refer to the entire class of molecules, both natural and synthetic.

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• opioids
• pediatric pain
• pediatric pharmacology