Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior.
Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior.
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作者：
Marino MJ;Terashima T;Steinauer JJ;Eddinger KA;Yaksh TL;Xu Q
我们提出的假说是，足底肉毒毒素B(Rimabotulinum oxin B：BONT-B)对外周传入终末释放功能有早期的局部影响，并随着时间的推移将被输送到初级传入的中央终末。一旦进入终末，它将裂解突触蛋白，阻止脊髓传入递质的释放，从而阻止脊髓伤害性兴奋和行为。在C57BL/6雄性小鼠中，单侧足底注射BoNT-B(1U)对小鼠的存活或运动功能没有影响，但同侧减少：i)足底福尔马林引起缩腿；ii)足底辣椒素引起后爪血浆外渗；iii)足底福尔马林引起背角SP释放(NK1受体内化)；iv)足底福尔马林引起背角神经元激活(CFO)；v)同侧背根神经节VAMP；这些结果表明，单侧足底注射后的BONT-B被外周终末摄取，局部活跃(阻止血浆外渗)，被运输到同侧背根节以裂解VAMP，并在突触前作用以阻断脊髓肽能终末的释放。鞘内SP后的观察结果为足底内BONT可能的跨突触效应提供了证据。这些结果提供了强有力的证据表明，外周BONT-B可以改变伤害性感受器的外周和中央终末释放，并通过突触前效应减弱下游的伤害性信息处理，进一步的证据表明可能存在突触后效应。
We addressed the hypothesis that intraplantar Botulinum toxin B (rimabotulinumtoxin B: BoNT-B) has an early local effect upon peripheral afferent terminal releasing function and over time will be transported to the central terminals of the primary afferent. Once in the terminals it will cleave synaptic protein, block spinal afferent transmitter release and thereby prevent spinal nociceptive excitation and behavior. In mice, C57Bl/6 males, intraplantar BoNT-B (1U), given unilaterally into the hind paw had no effect upon survival or motor function but ipsilaterally decreased: i) intraplantar formalin evoked flinching; ii) intraplantar capsaicin evoked plasma extravasation in the hindpaw measured by Evans blue in the paw; iii) intraplantar formalin evoked dorsal horn SP release (NK1 receptor internalization); iv) intraplantar formalin evoked dorsal horn neuronal activation (cFos); v) ipsilateral DRG VAMP; vi) ipsilateral SP release otherwise evoked bilaterally by intrathecal capsaicin; vii) ipsilateral activation of cFos otherwise evoked bilaterally by intrathecal substance P. These results indicate that BoNT-B after unilateral intraplantar delivery is taken up by the peripheral terminal, is locally active (blocking plasma extravasation), is transported to the ipsilateral DRG to cleave VAMP and is acting presynaptically to block release from the spinal peptidergic terminal. The observations following intrathecal SP offer evidence for a possible transsynaptic effect of intraplantar BoNT. These results provide robust evidence that peripheral BoNT-B can alter peripheral and central terminal release from a nociceptor and attenuate downstream nociceptive processing via a presynaptic effect, with further evidence suggesting a possible postsynaptic effect.
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