Effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of dorsal root ganglion neurons in a neuropathic pain model

We hypothesized that abnormal activity and adrenergic sensitivity in injure d dorsal root ganglion (DRG) neurons are due to an intrinsic alteration of the cell body membrane. We investigated the effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of DRG neurons in a rat chronic c onstriction injury (CCI) model. At first, we demonstrated thermal hyperalge sia and sprouting sympathetic nerve fibers in the ipsilateral L4-L5 DRGs. U sing whole-cell patch clamp techniques, we found that alpha(2)-adrenergic s timulus by 10 mu M norepinephrine (NE) inhibited inward currents (I-Ba, Ba2 + as a charge carrier) through voltage-dependent Ca2+ channels (VDCCs) of D RGs in the CCI model by 42%, whereas it enhanced the I-Ba by 18% in control animals. The inhibitory effect of NE disappeared by pretreatment with the N-type VDCC antagonist omega-conotoxin GVIA (1 mu M). NE shifted the inacti vation curve to a more negative potential, showing that it has inhibitory e ffects on I-Ba both in activated and in inactivated states. alpha(2)-Adrene rgic stimulus also inhibited outward K+ currents by 24% in the CCI model, w hile it had no effect on the currents in control animals. The inhibitory ef fect of NE was blocked by pretreatment with the Ca2+-activated K+ (K-Ca) ch annel antagonist charybdotoxin (40 nM). The NE-induced inhibitory effects b oth on N-type VDCC and on K-Ca channels in injured DRG neurons of the CCI m odel could lead to cell membrane depolarization, resulting in a spontaneous discharge of action potential and an increase in sensitivity to adrenergic stimulus. (C) 1999 Elsevier Science B.V. All rights reserved.