Temporal and Spatial Profiles of Pontine-Evoked Monoamine Release in the Rat's Spinal Cord

Abstract

In the spinal cord, the monoamine neurotransmitter norepinephrine, which is released mainly from fibers descending from the dorsal pons, has major modulatory effects on nociception and locomotor rhythms. To map the spatial and temporal patterns of this release, changes in monoamine level were examined in laminae I–VIII of lumbar segments L3–L6 of halothane-anesthetized rats during pontine stimulation. The changes were measured through a carbon fiber microelectrode at 0.5-s intervals by fast cyclic voltammetry, which presently is the method of best spatiotemporal resolution. When different pontine sites were tested with 20-s pulse trains (50-to 200-μA amplitude, 0.5-ms pulse width, and 50-Hz frequency) during measurement in the dorsal horn (lamina IV), the largest consistent increases were produced by the locus ceruleus, although effective pontine sites extended 1.5 mm dorsally and ventral from the locus ceruleus. When the locus ceruleus stimulus was used to map the spinal cord, increased levels were always seen in lamina I and laminae IV–VIII, whereas 50% of sites in laminae II and III showed substantial decreases and the rest showed increases. These increases typically had short latencies [4.5 ± 0.4 (SE) s] and variable decay times (5–200 s), with peaks occurring during the stimulus train (mean rise-time: 12.0 ± 0.6 s). The mean peak level was 544 ± 82 nM as estimated from postexperimental calibration with norepinephrine. Other significant laminar differences included higher mean peak concentrations (805 nM) and rise times (14.9 s) in lamina I and shorter latencies in lamina VI (3.2 s). Peak concentrations were inversely correlated with latency. When stimulation frequency was varied, increases were disproportionately larger with faster frequencies (≥50 Hz), hence extrajunctional overflow probably contributed most of the signal. We conclude, generally, that pontine noradrenergic control is exerted on widespread spinal laminae with a significant component of paracrine transmission after several seconds of sustained activity. Relatively stronger effects prevail where nociceptive transmission (lamina I) and locomotor rhythm generation (lamina VI) occur.