The biologic actions of opioids are exerted via interactions with the three major opioid receptor types, μ, δ, and κ, and opioid binding is distributed throughout the central nervous system (Mansour et al., 1988). It is thus not surprising that morphine and other narcotic analgesics produce not only analgesia but changes in respiratory, cardiovascular, gastrointestinal, and neuroendocrine functions when given systemically. For this reason, microinjection mapping studies, in which opioid agonists are applied directly within discrete brain regions, have been used to identify those central nervous system sites at which opioid agonist binding gives rise to analgesia. These studies point to a limited number of brain sites supporting opioid analgesia, the most important and best studied being the midbrain periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) (Mayer and Price, 1976; Yaksh et al., 1988). The PAG and RVM are links in an opioid-sensitive nociceptive modulating network that spans the neuraxis, yet each has within it all of the neuronal machinery necessary to induce analgesia. Understanding that machinery, as well as how the relationships between opioid-sensitive brain regions give rise to the properties of the network as a whole, continues to be a central goal for researchers concerned with nociceptive modulation.

The anatomic organization of this nociceptive modulating network is shown schematically in Figure 3.1. The RVM sends a substantial descending projection through the dorsolateral funiculus to the dorsal horn, with terminations in those layers implicated in nociceptive processing.