Spinal pain processing mechanisms undergo dramatic changes during postnatal development and mature earlier at rostral than caudal spinal levels. This raises the possibility that the pharmacology of pain control in the neonatal chord may differ from that of the adult. Yet basic research is scarce regarding the developmental pharmacology of the spinal chord. The dorsal horn is an important site for study as it represents the location where spinal pain-transmitting (afferent peptide) and pain- modulating (bulbospinal monoamine) systems first converge. Given the maturational changes proceed rostro-caudally, independent analyses of rostral and caudal spinal levels (versus whole spinal chord) are required to avoid erroneous interpretation of developmental events. Consequently, these studies examine the developmental pharmacology of pain processing mechanisms in the spinal chord dorsal horn at cervical and lumbar spinal levels and employ a number of techniques including spinal slice perfusion, RIA, and HPLC.
The specific aims target the cervical and lumbar enlargements and: 1) characterize maturational changes in dorsal horn transmitter levels of primary afferent substance P (SP) and calcitonin gene-related peptide (CGRP), and bulbospinal noradrenaline (NA) and serotonin (5-HT), 2) examine the evoked release of these neurotransmitters across age, 3) define the pharmacology of monoamine receptor systems that modulate the spinal release of SP and CGRP, and 4) study the development of the functional uptake and release of monamines by bulbospinal terminals. These studies will provide important new information about the developmental pharmacology of spinal pain processing and how they compare to those of the adult.
| Yaksh, T L; Dirig, D M; Conway, C M et al. (2001) The acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugs and release of spinal prostaglandin E2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1. J Neurosci 21:5847-53 |
