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 immunoreactive (ir)-substance P and ir-neurokinin A are released in the region of the substantia gelatinosa of the spinal cord when impulses arrive in nociceptors. Particularly with ir-neurokinin A, rapid inactivation does not appear to occur, resulting in the released neuropeptides accessing sites relatively remote from sites of release. Microprobes have also provided evidence that the sites accessed by ir-substance P are controlled by spinal cord peptidases and that peptidase inhibition by the endogenous neuropeptide calcitonin gene-related peptide expands the distribution of sites reached. Inflammatory joint disease results in a relatively massive central release of ir-substance P when the damaged joints are flexed or compressed. Antibody microprobe studies of the spinal release of ir-galanin have favored release from intrinsic spinal neurons 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 stimuli but it is uncertain whether this results from release predominantly from primary afferents or intrinsic spinal neurons. Studies using antibody microprobes inserted into the brain have detected the release of ir-substance P in the ventral region of the striatum following administration of amphetamine. Microprobes have also followed peptide release from striatal terminals in substantia nigra and have provided evidence of a basal presence of ir-neurokinin A but not of substance P. Depletion of the dopamine input to the striatum, or blockade of dopamine receptors, caused considerable reduction of ir-neurokinin A released within the substantia nigra.
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, United Kingdom.
A W
AW
Duggan
L J
LJ
Furmidge
D000818:Animals; D001921:Brain / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D009619:Nociceptors / Q000502:physiology; D010146:Pain; D013116:Spinal Cord / Q000502:physiology*; D015320:Tachykinins / Q000378:metabolism
D009479:Neuropeptides; D015320:Tachykinins