Among the intrinsic bioelectrical properties of deep dorsal horn neurons (DHNs), Ca²⁺-dependent plateau potentials play a major role in processing of nociceptive information. In the first part of the talk, I will present the inhibitory GABA_B modulation of plateau-generating DHNs and the ionic basis of this control.

Application of the GABA_B agonist baclofen on rat spinal cord slices induced a hyperpolarization of the DHNs, associated with a decrease in input resistance. V-I relationships indicated the activation of potassium conductances. Baclofen also reduced the amplitude and duration of plateau potentials. Using whole cell voltage-clamp recordings, we further examined potassium currents activated by baclofen. Bath-application of the agonist induced outward current at resting potential that reversed near the K⁺ equilibrium potential. The cord conductance increased for more negative potentials. The current was sensitive to the inward rectifier channels (KIR₃) blockers Cs⁺ and Ba²⁺ at low concentrations. Baclofen-induced current was blocked by the GABA_B antagonist CGP55845. Baclofen also reduced a dihydropyridine-sensitive Ca²⁺ current. Inhibition of DHN plateau properties via induction of a KIR current and inhibition of a Ca²⁺ current could underlie the antinociceptive effect of GABA_B agonists.

In the second part of this abstract, I will show that the GABA_B-receptor-mediated inhibitory modulation of deep DHNs is dynamically balanced by an excitatory modulation via mGlu receptors. This dual modulation has a profound impact on processing of sensory information in the dorsal horn. Deep DHNs present three possible types of firing: (i) tonic discharge, (ii) plateau potentials, and (iii) oscillations and rhythmic bursts. The proportion of each type of firing depends on sustained modulatory inputs. In basal condition, the tonic state is predominant (90.2 % of cells), and oscillations almost inexistent. When GABA_B receptors are blocked (CGP55845) or group I mGluRs activated (ACPD/DHPG) a much larger proportion of neurons expressed plateau potentials (respectively 46.15 % and 45.9 %). Rhythmic bursts are elicited in 8 % of the cells only when mGluRs are activated. Finally, when ACPD and CGP55845 are applied together, the majority of the neurons (90 %) display regenerative properties, i.e. 60 % rhythmic bursts and 30 % plateau potentials. These effects partly relied on the modulation of an inwardly rectifying K⁺ current (Kir3), activated by the GABA_B agonist baclofen and depressed by DHPG. Immunohistochemical analysis showed that DHNs with plateau properties are contacted by both GABAergic and glutamatergic input.

Using the hybrid network technique, connecting a model of a nociceptive afferent fibre to a biological DHN, we investigated the incidence of the firing type on input-output transfer. The significant differences in the cross-correlation and contribution indexes between afferent and DHN spikes indicate that the three modes of firing impose three different functional states to nociceptive signal transmission. Each state could preferentially participate to different pathophysiological conditions: acute nociceptive transmission, pain sensitisation, and loss of coding related to chronic pain.

This work was supported by the Conseil Régional d’Aquitaine (20010301213), the DGA (01.34.012.00470.75.01), the Institut UPSA de la douleur, the FRM (ARI20010406005/1), and the Singer-Polignac fundation.