Effects of corticotropin-releasing factor on plasticity of optically recorded neuronal activity in the substantia gelatinosa of rat spinal cord slices.

We examined the effects of corticotropin-releasing factor (CRF) on plasticity of optically recorded neuronal activity in the substantia gelatinosa (lamina II) of 12-18-day-old rat spinal cord slices stained with a voltage-sensitive dye. Single-pulse test stimulation to the dorsal root that activated A and C fibres evoked prolonged (>100 ms) light-absorption change in the lamina II. This response represents the gross membrane potential change of all elements along the slice depth. After conditioning high-frequency stimulation of A-fibre-activating strength, test stimulus elicited less neuronal activity [-27+/-1% (7), (average+/-SE (n)), P<0.01 (*) at 45-60 min after conditioning]. When CRF (1 microM, 10 min) was applied during conditioning, the neuronal activity was facilitated rather than suppressed [+20+/-3% (5), P<0.05]. CRF alone exhibited insignificant effect [-5+/-1% (4), P=0.2]. In the presence of the inhibitory amino acid antagonists bicuculline (1 microM) and strychnine (0.3 microM) in the perfusate, in contrast, the conditioning facilitated it [+27+/-1% (12)*], and CRF treatment during conditioning inhibited the facilitation dose-dependently [0.1 microM: +18+/-2% (5)*, 1 microM: +13+/-1% (7)*]. Although interneuronal actions might contribute, these results suggest that CRF may have dual effects on excitatory synaptic transmission within the lamina II depending upon cellular conditions: a conversion from the induction of long-term depression to long-term potentiation (LTP), and inhibition of LTP induction. Since the LTP is thought to be responsible at least in part for the persistent pain, CRF could regulate the induction.