کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6275515 | 1614856 | 2012 | 11 صفحه PDF | دانلود رایگان |

Persistent inflammation is associated with a shift in spinal GABAA signaling from inhibition to excitation such that GABAA-receptor activation contributes to inflammatory hyperalgesia. We tested the hypothesis that the primary afferent is the site of the persistent inflammation-induced shift in GABAA signaling which is due to a Na+-K+-Clâ-co-transporter (NKCC1)-dependent depolarization of the GABAA current equilibrium potential (EGABA). Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion (DRG) neurons from naïve and inflamed (3Â days after a subcutaneous injection of complete Freund's adjuvant) adult male rats were studied with Ca2+ imaging, western blot and gramicidin-perforated patch recording. GABA evoked a Ca2+ transient in a subpopulation of small- to medium-diameter capsaicin-sensitive cutaneous neurons. Inflammation was associated with a significant increase in the magnitude of GABA-induced depolarization as well as the percentage of neurons in which GABA evoked a Ca2+ transient. There was no detectable change in NKCC1 protein or phosphoprotein at the whole ganglia level. Furthermore, the increase in excitatory response was comparable in both HEPES- and HCO3--buffered solutions, but was only associated with a depolarization of EGABA in HCO3--based solution. In contrast, under both recording conditions, the excitatory response was associated with an increase in GABAA current density, a decrease in low threshold K+ current density, and resting membrane potential depolarization. Our results suggest that increasing K+ conductance in afferents innervating a site of persistent inflammation may have greater efficacy in the inhibition of inflammatory hyperalgesia than attempting to drive a hyperpolarizing shift in EGABA.
⺠There is a persistent inflammation-induced shift in spinal GABAA signaling. ⺠This is thought to be due to an NKCC1-dependent depolarization of EGABA in nociceptive afferents. ⺠Our results suggest other mechanisms contribute to the shift. ⺠These include a depolarization of Vrest, an increase in IGABA and a decrease in low threshold IK. ⺠A HCO3--dependent exchanger also plays an important role in the determination of EGABA.
Journal: Neuroscience - Volume 220, 18 September 2012, Pages 330-340