administration of naloxone, a specific opioid antagonist, can block the effects of both electric stimulation and opioid administration. In humans, electric stimulation in periaqueductal and periventricular structures produces an analgesia that can be attenuated by the administration of naloxone (e.g., Hosobuchi et al., 1977).

On the basis of such findings, it was proposed and later established that the CNS has its own naturally occurring opioids. It is now known that there are three major families of endogenous opioid peptides, each the product of a different gene: the enkephalins, the dynorphins, and the endorphins. In addition to the opioid peptides, which probably contribute to analgesic processes in the CNS in a more localized fashion via relatively short neural circuits, longer, chemically specific descending neural systems containing norepinephrine or serotonin play major roles in the modulation of pain (Figure 2-2). Descending norepinophrine- or serotonin-containing pathways, originating in the medulla and pons, affect the output of wide-dynamic-range and nociceptive-specific neurons and alter responsiveness to noxious inputs.

The multiple descending circuits, probably interacting with opioid peptide-containing neurons in the spinal cord or brainstem, underlie the behavioral modulation of pain. In a more general sense, the descending and local circuits are mechanisms by which an organism extracts useful information from its environment. The identification of the multiple pain-suppressing pathways has led to a search for their physiologic role under natural conditions. Some forms of stress, fear, exercise, and disease states (e.g., hypertension), including pain itself, appear to activate the pathways. However, we still have only a few clues as to the role of the descending control systems in the processing of sensory information under ordinary behavioral conditions.

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