Substance P and NMDA receptor-mediated slow potentials in neonatal rat spinal cord: age-related changes.

ABSTRACT

Slow ventral root potentials (slow VRP's) recorded from 1- to 5-day-old rat spinal cords are implicated in nociception, but there is controversy over their origin and persistence in the adult. The present study investigated changes in the role of substance P and NMDA receptors in slow VRP generation during the postnatal period (1-21 days). Through 9 days, dorsal root stimulation elicits slow VRP's with typical peak amplitudes at 3-4 s, decay time constants of 18-20 s, and durations > 20 s. After 11 days, peak amplitude shortens to < 1 s, decay time constant 4-5 s, and duration < 10 s. At 1-6 days, slow VRP's are sensitive to the NMDA receptor antagonist APV and the substance P antagonists spantide and CP 96,345. After 11 days, APV sensitivity is retained, but spantide and ability of substance P to evoke a response are diminished. Abbreviated slow VRP's in post-11-day spinal cords appear to correspond to the early APV-sensitive component of long-duration slow VRP's in younger animals. Attempts to restore long-duration slow VRP's in 12- to 14-day-old rat cords by blocking various inhibitory mechanisms were not successful. The results suggest that a substance P response, some of which is mediated by NK1 receptors, is lost with maturation of the cord. Either a developmental role played by substance P changes with maturity, or the motor neurons of the isolated post-11-day cord lose the capacity to sustain large long-duration plateau potentials.