Activation of interleukin-1beta receptor suppresses the voltage-gated potassium currents in the small-diameter trigeminal ganglion neurons following peripheral inflammation

Mamoru Takeda, Junichi Kitagawa, Masayuki Takahashi, Shigeji Matsumoto
Pain 2008 October 31, 139 (3): 594-602
The glial cytokine, interleukin-1beta (IL-1beta), potentiates the excitability of nociceptive trigeminal ganglion (TRG) neurons via membrane depolarization following peripheral inflammation. Perforated patch-clamp technique was used this study to show that the mechanism underlying the excitability of small-diameter TRG neurons following inflammation is due to IL-1beta. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad. The TRG neurons innervating the site of inflammation were identified by fluorogold (FG) labeling. The threshold for escape from mechanical stimulation applied to the orofacial area in inflamed rats was significantly lower than observed for control rats. IL-1beta at 1nM suppressed total voltage-gated K(+) currents in most TRG neurons (70%) under voltage-clamp conditions in control and inflamed rats. IL-1beta significantly decreased the total, transient (I(A)) and sustained (I(K)) currents in FG-labeled small-diameter TRG neurons in both groups. The IL-1beta-induced suppression of TRG neuron excitability was abolished by co-administration of ILra, an IL-1beta receptor blocker. The magnitude of inhibition of I(A) and I(K) currents by IL-1beta was significantly greater in inflamed rats than in controls. IL-1beta inhibited I(A) to a significantly greater extent than I(K). These results suggest that the inhibitory effect of I(A) and I(K) currents by IL-1beta in small-diameter TRG neurons potentiates neuronal excitability thereby contributing to trigeminal inflammatory hyperalgesia. These findings provide evidence for the development of voltage-gated K(+) channel openers and IL-1beta antagonists as therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.

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