PROBING THE BRAIN AND SPINAL-CORD WITH NEUROPEPTIDES IN PATHWAYS RELATED TO PAIN AND OTHER FUNCTIONS

The principles involved in the fabrication and use in vivo of antibody microprobes are described. These devices have shown that immunoreacti ve (ir)-substance P and ir-neurokinin A are released in the region of the substantia gelatinosa of the spinal cord when impulses arrive in n ociceptors. Particularly with ir-neurokinin A, rapid inactivation does not appear to occur, resulting in the released neuropeptides accessin g sites relatively remote from sites of release. Microprobes have also provided evidence that the sites accessed by ir-substance P are contr olled by spinal cord peptidases and that peptidase inhibition by the e ndogenous neuropeptide calcitonin gene-related peptide expands the dis tribution of sites reached. Inflammatory joint disease results in a re latively massive central release of ir-substance P when the damaged jo ints are flexed or compressed. Antibody microprobe studies of the spin al release of ir-galanin have favored release from intrinsic spinal ne urons rather than from primary afferent terminals following peripheral noxious stimuli. Immunoreactive-somatostatin was found to be released following noxious thermal but not noxious mechanical peripheral stimu li but it is uncertain whether this results from release predominantly from primary afferents or intrinsic spinal neurons. Studies using ant ibody microprobes inserted into the brain have detected the release of ir-substance P in the ventral region of the striatum following admini stration of amphetamine. Microprobes have also followed peptide releas e from striatal terminals in substantia nigra and have provided eviden ce of a basal presence of ir-neurokinin A but not of substance P. Depl etion of the dopamine input to the striatum, or blockade of dopamine r eceptors, caused considerable reduction of ir-neurokinin A released wi thin the substantia nigra.