Anatomy of the Opioid-Systems of the Brain

Extract

In 1969, Roger Guillemin and Andrew Schally independently reported the isolation and identification of the first hypothalamic neuropeptide, thyrotropin releasing factor (TRF). Following this landmark event in neuroendocrinology the ensuing years have witnessed a cascade of isolations of new neuropeptides and a virtual revolution in neurobiology. The discipline of neuroendocrinology has been remarkably impacted by the evidence that all of the “hypophysiotrophic” releasing factors presently identified are distributed widely throughout the brain with neurotransmitter or neuromodulator roles quite different from their actions of regulating the secretion of pituitary hormones. The study of these neuropeptide systems in activity of the central nervous system looms as one of the most exciting and significant eras in brain research. Although it is premature to assign specific roles for the presently known neuropeptides in pathogenesis of neurological diseases, our limited current knowledge already points to a numberof syndromes and clinical disorders which may be related to neuropeptide imbalance. Congential insensitivity to pain undoubtedly involves several peptide systems including Substance P, enkephalin, somatostatin and the endorphins. The opiocortins (β-endorphin, ACTH) of the brain as well as those of the pituitary gland are directly involved in the homeostatic mechanisms brought into action by such trauma as brain and spinal cord injury, septic shock and hemorrhage. The role of peptides in regulation of cerebral circulation will likely be identified with the etiology of stroke and the production of painful hemicranial syndromes. Among the most prevelant disorders of the human nervous system are the dementias and psychoses (Alzheimer’s disease, schizophrenia); subtle changes in brain peptide and receptor activity are being considered as responsible contributors to these diseases.