Brain stem neuronal circuitry underlying the antinociceptive action of opiates

This chapter discusses the brain stem neuronal circuitry underlying the antinociceptive action of opiates. Opiates are the most potent and reliable analgesic agents. They are of great clinical value because their action on pain is selective: consciousness, motor function, and sensory function other than pain are spared at the usual analgesic doses. Opiates produce analgesia by an action at highly selective receptors located at specific anatomical sites within the central nervous system. The midbrain periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) are brain stem components of a network that controls nociceptive transmission at the level of the spinal cord. Opiates injected at the brain stem elicit analgesia at doses that are orders of magnitude lower than those required to elicit an equianalgesic effect by systemic administration. Cutting the spinal dorsolateral funiculus, which contains descending projections from the RVM, reduces the effectiveness of a given dose of systemically administered morphine. Injection of the opiate antagonist naloxone into the RVM reverses the analgesic effect of systemically administered opiates. Thus, the RVM and PAG contribute to the analgesic effect of systemically administered opiates.