Cellular mechanism for spinal cord electrical stimulation-induced analgesia

Spinal cord electrical stimulation (SCS) is the most commonly used implantable neuro stimulation modality for the management of pain syndromes. However, cellular mechanisms of SCS-evoked analgesia have been poorly understood at this time. In the present study, whole-cell patch-clamp recordings were performed from substantia gelatinosa (SG) neurons in adult rat spinal cord slices to determine which neurotransmitters are influenced by SCS. Although repetitive stimuli applied to the dorsal root did not induce any slow responses, ones focally applied to the spinal dorsal horn produced slow inhibitory postsynaptic currents (IPSCs) at a holding potential of -50 mV in about 30% of the SG neurons recorded. The amplitude and duration of slow IPSCs increased with the number of stimuli and decreased with removal of Ca2+ from the external Krebs solution. Slow IPSCs were associated with an increase in membrane conductance; their polarity was reversed at a potential close to the equilibrium potential for K+, calculated from the Nernst equation. Slow IPSCs were blocked by addition of GDP-beta-S into the patch-pipette solution, reduced in amplitude in the presence of Ba2+, and significantly suppressed in the presence of an antagonist of GIRK channels, tertiapin-Q. Somatostatin produced an outward current in a subpopulation of SG neurons and the slow IPSC was occluded during the somatostatin-induced outward current. Moreover, slow IPSCs were significantly inhibited by a somatostatin receptor antagonist, cyclo-somatostatin. These results indicate that endogenous somatostatin released from interneurons or descending fibers by SCS may induce slow IPSCs by activating GIRK channels in SG neurons. It is suggested that this slow synaptic transmission may play an important role in SCS-evoked analgesia.