Kim Min Ji, Park Young Hong, Yang Kui Ye, Ju Jin Sook, Bae Yong Chul, Han Seong Kyu, Ahn Dong Kuk
Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
Korean J Physiol Pharmacol. 2017 Jan;21(1):65-74. doi: 10.4196/kjpp.2017.21.1.65. Epub 2016 Dec 21.
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABA receptors under inflammatory pain conditions.
在此，我们研究了机械性异常性疼痛的中枢处理机制，发现其与伤害性神经元的低阈值输入存在直接兴奋性联系。实验选用体重230 - 280 g的雄性Sprague-Dawley大鼠。皮下注射白细胞介素1β（IL-1β）（1 ng/10 µL）用于产生机械性异常性疼痛和热痛觉过敏。脑池内注射γ-氨基丁酸A（GABA）受体拮抗剂荷包牡丹碱，在正常条件下可在口面部区域产生机械性异常性疼痛。然而，在炎性疼痛条件下，脑池内注射荷包牡丹碱（50 ng）产生了矛盾的抗异常性疼痛效应。用树脂毒素（RTX）预处理，其可耗尽初级传入纤维中的辣椒素受体蛋白，并未改变脑池内注射荷包牡丹碱所产生的矛盾抗异常性疼痛效应。脑池内注射布美他尼，一种钠-钾-氯共转运体（NKCC 1）抑制剂，可逆转IL-1β诱导的机械性异常性疼痛。在对照组中，应用GABA（100 µM）或蝇蕈醇（3 µM）在短杆菌肽穿孔电流钳模式下导致膜超极化。然而，在一些神经元中，应用GABA或蝇蕈醇在IL-1β处理的大鼠中导致膜去极化。这些结果表明，在炎性疼痛条件下，一些有髓大Aβ纤维可进入伤害性系统并通过GABA受体引发疼痛感觉。
