Contribution of activated interleukin receptors in trigeminal ganglion neurons to hyperalgesia via satellite glial interleukin-1β paracrine mechanism

The present study investigated whether under in vivo conditions, inflammation alters the excitability of nociceptive A delta-trigeminal ganglion (TRG) neurons innervating the facial skin via a cytokine paracrine mechanism. We used extracellular electrophysiological recording with multibarrel-electrodes in this study, and complete Freund's adjuvant (CFA) was injected into the rat facial skin. The threshold for escape from mechanical stimulation applied to the whisker pad area in inflamed rats (2 days after CFA injection) was significantly lower than that in control rats. A total of 45 A delta-nociceptive-TRG neurons responding to electrical stimulation of the whisker pad were recorded in pentobarbital-anesthetized rats. The number of A delta-TRG neurons with spontaneous firings and their firing rate in inflamed rats were significantly larger than those in control rats. The firing Fates of the A delta-TRG neuronal spontaneous activity were current-dependently decreased by local iontophoretic application of an interleukin I receptor type I antagonist (IL-1ra) in inflamed rats, but not in controls, and current-dependently increased by iontophoretic application of interleukin 1 (IL-1 beta) in both control and inflamed rats. IL-1ra also inhibited A delta-TRG neuron activity evoked by mechanical stimulation in the inflamed rats. The mechanical threshold of nociceptive-TRG neurons in inflamed rats was significantly lower than that in control rats, but was not significantly different between control and inflamed rats after application of an IL-1ra. These results suggested that inflammation modulates the excitability of nociceptive A delta-TRG neurons innervating the facial skin via IL-1 beta paracrine action within trigeminal ganglia. Such an IL-1 beta release could be important in determining trigeminal inflammatory hyperalgesia. (C) 2008 Elsevier Inc. All rights reserved.