The neural circuitry that mediates analgesia produced by opiates and other drugs in the adult has been intensively studied and as a result there is a clearer understanding of brain mechanisms that function to process or temper noxious information. Yet virtually nothing is known of these systems in the immature organism. The experiments proposed in this project examine the maturation of a particular endogenous neural system that modulates painful somatosensory information processing. That system is the periaqueductal grey of the midbrain (PAG) and its connections to more caudal brain structures (likely medullary) that project to the dorsal horn of the spinal cord to inhibit the response to painful stimulation. On the basis of substantial preliminary data it is clear that this system is not mature in the preweanling rat. There are two major goals of the proposed experiments. The first is to define in detail the changes in the anatomical organization of PAG receptors that develop in parallel with analgesia. Using well defined paradigms to stimulate the PAG with opiate (mu, delta, kappa) and glutamate (kainic acid, NMDA, quisqualate) agonists, the maturation of analgesia will be tested with thermal and mechanical stimuli over a range of intensities. The second goal is to define anatomically changes in the indirect projections through the medulla of the PAG to the spinal cord that correspond to the behavioral analgesia. This will be accomplished by labeling the tracts from the PAG and the dorsal horn of the spinal cord to the medulla at different ages, by determining the neurotransmitter content of the cells impinged on by the PAG that also project to the spinal cord and by studying the developmental appearance of each receptor type as defined autoradiographically. The studies therefore should provide new and important information about the development of the analgesia induced by stimulation of the PAG in the developing animal. An understanding of those developmental processes will also provide insight on the organization and function of similar neural processes in the adult.
