Chapter 18

### INTRODUCTION

Pain is a component of virtually all clinical pathologies, and management of pain is a primary clinical imperative. Opioids are a mainstay of pain treatment, but rational therapy may involve, depending upon the pain state, one or more drug classes, such as NSAIDs, anticonvulsants, and antidepressants. The properties of these non-opioid agents are presented in Chapters 34, 21, 15. This chapter focuses first on the biochemical, pharmacological, and functional nature of the opioid system that defines the effects of opioids on pain processing, gastrointestinal-endocrine-autonomic functions, and reward-addiction circuits. Subsequently, the chapter presents principles that guide the use of opioid and non-opioid agents in the management of clinical pain states.

The term opiate refers to compounds structurally related to products found in opium, a word derived from opos, the Greek word for "juice," natural opiates being derived from the resin of the opium poppy, Papaver somniferum. Opiates include the natural plant alkaloids, such as morphine, codeine, thebaine, and many semisynthetic derivatives. An opioid is any agent, regardless of structure, that has the functional and pharmacological properties of an opiate. Endogenous opioids, many of which are peptides, are naturally occurring ligands for opioid receptors found in animals. The term endorphin is used synonymously with endogenous opioid peptides but also refers to a specific endogenous opioid, β-endorphin. The term narcotic was derived from the Greek word narkotikos, for "benumbing" or "stupor." Although narcotic originally referred to any drug that induced narcosis or sleep, the word has become associated with opioids and is often used in a legal context to refer to a variety of substances with abuse or addictive potential.

History. The first undisputed reference to opium is found in the writings of Theophrastus in the third century B.C. Arab physicians were well-versed in the uses of opium; Arab traders introduced the drug to the Orient, where it was employed mainly for the control of dysentery. By 1680, Sydenham was lauding opium: "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium."

Opium contains >20 distinct alkaloids. In 1806, Frederich Sertürner, a pharmacist's assistant, reported the isolation by crystallization of a pure substance in opium that he named morphine, after Morpheus, the Greek god of dreams. By the middle of the 19th century, the use of pure alkaloids in place of crude opium preparations began to spread throughout the medical world, an event that coincided with the development of the hypodermic syringe and hollow needle, permitting direct delivery of such water-soluble formulations "under the skin" into the body.

In addition to the remarkable beneficial effects of opioids, the side effects and addictive potential of these drugs also have been known for centuries. In the civil war in the U.S., the administration of "soldier's joy" often led to "soldier's disease," the opiate addiction brought about by medication of chronic ...

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