Hawkins Jordan L, Cornelison Lauren E, Blankenship Brian A, Durham Paul L
Missouri State University, Springfield, MO, USA.
Pain Rep. 2017 Oct 17;2(6):e628. doi: 10.1097/PR9.0000000000000628. eCollection 2017 Nov.
Although neck muscle tension is considered a risk factor for migraine, pungent odors can act as a trigger to initiate an attack in sensitized individuals. Although noninvasive vagus nerve stimulation (nVNS) is now an approved treatment for chronic migraine, how it functions to inhibit trigeminal nociception in an episodic migraine model is not known.
The objectives of this study were to determine if nVNS could inhibit trigeminal nociception in a novel model of episodic migraine and investigate changes in the expression of proteins implicated in peripheral and central sensitization.
Sprague-Dawley male rats were injected with an inflammatory agent in the trapezius muscle before exposure to pungent volatile compounds, which was used to initiate trigeminal nociceptor activation. The vagus nerve was stimulated transdermally by a 1-ms pulse of 5 kHz sine waves, repeated at 25 Hz for 2 minutes. Nocifensive head withdrawal response to von Frey filaments was determined and immunoreactive protein levels in the spinal cord and trigeminal ganglion (TG) were investigated.
Exposure to the pungent odor significantly increased the number of nocifensive withdrawals in response to mechanical stimulation of sensitized TG neurons mediated by neck muscle inflammation. Noninvasive vagus nerve stimulation inhibited nociception and repressed elevated levels of P-ERK in TG, Iba1 in microglia, and GFAP in astrocytes from sensitized animals exposed to the pungent odor.
Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine.
尽管颈部肌肉紧张被认为是偏头痛的一个风险因素，但刺鼻气味可作为触发因素，引发敏感个体的偏头痛发作。虽然非侵入性迷走神经刺激（nVNS）现已被批准用于治疗慢性偏头痛，但其在发作性偏头痛模型中抑制三叉神经伤害感受的作用机制尚不清楚。
本研究的目的是确定nVNS是否能在一种新的发作性偏头痛模型中抑制三叉神经伤害感受，并研究与外周和中枢敏化相关的蛋白质表达变化。
在将Sprague-Dawley雄性大鼠暴露于刺鼻挥发性化合物之前，先在其斜方肌中注射一种炎症介质，以启动三叉神经伤害感受器的激活。通过5kHz正弦波的1ms脉冲经皮刺激迷走神经，以25Hz重复刺激2分钟。测定对von Frey细丝的伤害性头部退缩反应，并研究脊髓和三叉神经节（TG）中的免疫反应性蛋白水平。
暴露于刺鼻气味显著增加了由颈部肌肉炎症介导的对致敏TG神经元机械刺激的伤害性退缩次数。非侵入性迷走神经刺激抑制了伤害感受，并抑制了暴露于刺鼻气味的致敏动物TG中P-ERK、小胶质细胞中Iba1和星形胶质细胞中GFAP的升高水平。
我们的研究结果表明，在一种新的发作性偏头痛啮齿动物模型中，nVNS抑制了机械性伤害感受，并抑制了与三叉神经元外周和中枢敏化相关的蛋白质表达。
