Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body

초록

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1a and cytokines levels including interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1a expression and IL-1b, IL-6, and TNF-a concentrations in the TG. Intraganglionic injection of PX-12, a HIF1a inhibitor, led to significant anti-allodynic effects and lowered the IL-1b, IL-6, and TNF-a levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1a associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. Perspective: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1a associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia. (c) 2022 by United States Association for the Study of Pain, Inc.

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