Glial cell line-derived neurotrophic factor modulates the excitability of nociceptive trigeminal ganglion neurons via a paracrine mechanism following inflammation
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- 作者：Mamoru Takeda ; m-takeda@tokyo.ndu.ac.jp ; Masayuki Takahashi ; Norifumi Hara ; Shigeji Matsumoto
- 关键词：Glial cell line-derived neurotrophic factor ; Paracrine ; Inflammation trigeminal ganglion neuron ; Single unit recording
- 刊名：Brain, Behavior, and Immunity
- 出版年：2013
- 出版时间：February, 2013
- 年：2013
- 卷：28
- 期：Complete
- 页码：100-107
- 全文大小：835 K
文摘
Previous our report indicated that acute application of glial cell line-derived neurotrophic factor (GDNF) enhances the neuronal excitability of adult rat small-diameter trigeminal ganglion (TRG) neurons, which innervate the facial skin in the absence of neuropathic and inflammatory conditions. This study investigated whether under in vivo conditions, GDNF modulates the excitability of nociceptive A¦Ä-TRG neurons innervating the facial skin via a paracrine mechanism following inflammation. We used extracellular electrophysiological recording with multibarrel-electrodes in this study. Spontaneous A¦Ä-TRG neuronal activity was induced in control rats after iontophoretic application of GDNF into the trigeminal ganglia (TRGs). Noxious and non-noxious mechanical stimuli evoked A¦Ä-TRG neuronal firing rate were significantly increased by iontophoretic application of GDNF. The mean mechanical threshold of nociceptive TRG neurons was significantly decreased by GDNF application. The increased discharge frequency and decreased mechanical threshold induced by GDNF were antagonized by application of the protein tyrosine kinase inhibitor, K252b. The number of A¦Ä-TRG neurons with spontaneous firings and their firing rates in rats with inflammation induced by Complete Freund¡¯s Adjuvant were significantly higher than control rats. The firing rates of A¦Ä-TRG spontaneous neuronal activity were significantly decreased by iontophoretic application of K252b in inflamed rats. K252b also inhibited A¦Ä-TRG neuron activity evoked by mechanical stimulation in inflamed rats. These results suggest that in vivo GDNF enhances the excitability of nociceptive A¦Ä-TRG neurons via a paracrine mechanism within TRGs following inflammation. GDNF paracrine mechanism could be important as a therapeutic target for trigeminal inflammatory hyperalgesia.