Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system

Abstract

To use an animal model to test whether migraine pain arises peripherally or centrally. We monitored the spontaneous and evoked activity of second-order trigeminovascular neurons in rats to test whether traffic increased following a potential migraine trigger (cortical spreading depression, CSD) and by what mechanism any such change was mediated. Neurons (n = 33) responded to stimulation of the dura mater and facial skin with A-δ latencies. They were spontaneously active with a discharge rate of 6.1 ± 6.4 discharges s(-1). Injection of 10 µg lignocaine into the trigeminal ganglion produced a fully reversible reduction of the spontaneous discharge rate of neurons. Neuronal discharge rate returned to normal by 90 min. Lignocaine reduced the evoked responses of neurons to dural stimulation to 37% and to facial skin stimulation to 53% of control. Induction of CSD by cortical injection of KCl increased the spontaneous discharge rate of neurons from 2.9 to 16.3 discharges s(-1) at 20 min post CSD. Injection of 10 µg lignocaine into the trigeminal ganglion at this time failed to arrest or reverse this increase. Injection of lignocaine prior to the initiation of CSD failed to prevent the subsequent development of CSD-induced increases in discharge rates. These results suggest that there is a continuous baseline traffic in primary trigeminovascular fibres and that CSD does not act to increase this traffic by a peripheral action alone - rather, it must produce some of its effect by a mechanism intrinsic to the central nervous system. Thus the pain of migraine may not always be the result of peripheral sensory stimulation, but may also arise by a central mechanism.