Subdiaphragmatic vagotomy increases the sensitivity of lumbar Ad primary afferent neurons along with voltage-dependent potassium channels in rats

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Ad sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K+ (IA) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Ad afferent neurons, which may be induced along with suppressing IA currents via the decreased expression of Kv4.3. Thus, peripheral Ad neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Synapse, 2012. (C) 2011 Wiley Periodicals, Inc.