Knight Yolande E, Bartsch Thorsten, Goadsby Peter J
Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Neurosci Lett. 2003 Jan 16;336(2):113-6. doi: 10.1016/s0304-3940(02)01250-8.
We have recently shown that injection of the P/Q-type (Ca(v)2.1/alpha(1A)) calcium channel blocker, omega-agatoxin IVA, into the periaqueductal gray (PAG) facilitates meningeal dural stimulation-evoked trigeminal nociceptive processing. We injected the GABA(A) antagonist bicuculline into the PAG in addition to the agatoxin and observed bicuculline's effect on neurons responding to dural stimulation recorded in the trigeminal nucleus caudalis of rats in order to determine if P/Q channel-mediated changes acted through GABAergic mechanisms. The inhibition of trigeminal nociceptive neurons characteristic of bicuculline administered into the PAG was maintained in the presence of blocked PAG P/Q-type calcium channels. This suggests the PAG descending pain modulatory pathway is not affected by P/Q-type calcium channel blockade at the postsynaptic GABAergic inhibitory interneuron and the facilitation produced by agatoxin is mediated by another mechanism. These findings have implications for disorders involving the PAG or P/Q-type channels, such as migraine, in particular for the development of preventative treatments, suggesting GABAergic and voltage-gated calcium channels could be separately modulated.
我们最近发现，向中脑导水管周围灰质（PAG）注射P/Q型（Ca(v)2.1/α(1A)）钙通道阻滞剂ω-芋螺毒素IVA，可促进硬脑膜刺激诱发的三叉神经伤害性处理。我们除了向PAG注射芋螺毒素外，还注射了GABA(A)拮抗剂荷包牡丹碱，并观察了荷包牡丹碱对大鼠三叉神经尾核中对硬脑膜刺激有反应的神经元的影响，以确定P/Q通道介导的变化是否通过GABA能机制起作用。在PAG的P/Q型钙通道被阻断的情况下，向PAG注射荷包牡丹碱所特有的对三叉神经伤害性神经元的抑制作用得以维持。这表明PAG下行性疼痛调制通路在突触后GABA能抑制性中间神经元处不受P/Q型钙通道阻断的影响，且芋螺毒素产生的促进作用是由另一种机制介导的。这些发现对涉及PAG或P/Q型通道的疾病（如偏头痛）具有启示意义，特别是对预防性治疗的开发，提示GABA能通道和电压门控钙通道可分别进行调节。
