The zebrafish: A model to study the endogenous mechanisms of pain

Abstract

The difficulty of designing new analgesic drugs is evident in the biochemical maze that results when an opioid agonist binds to opioid receptors, triggering a complex cascade of intracellular mechanisms. In an effort to enhance understanding of the biochemical and pharmacological mechanisms that are responsible for the action of opioid drugs, we describe the characterization of the zebrafish opioid system, a novel experimental approach to unravel the molecular mechanisms that underlie opioid activity. We have cloned the zebrafish opioid receptors and peptides, established their expression pattern during development and in the adult organism, and determined their pharmacological profiles and biochemical properties. Furthermore, developmental studies in the zebrafish yield valuable information about the developmental roles of the opioid receptors. Building on these findings, we show that the zebrafish opioid receptors and peptides present molecular, pharmacological, and biochemical profiles that are fundamentally similar to those of their mammalian counterparts and from which results can therefore be extrapolated to higher vertebrates. Thus the zebrafish represents a straightforward model to study opioid activity, and can be very useful not only for the analysis of the complex endogenous systems that regulate the action of opioid agents but also for in vivo tests of novel analgesic drugs.