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Gulf War agents pyridostigmine bromide and permethrin cause hypersensitive nociception that is restored after vagus nerve stimulation
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-09-29 , DOI: 10.1016/j.neuro.2018.09.007
Damir Nizamutdinov , Sanjib Mukherjee , Chenghao Deng , Harald M. Stauss , Lee A. Shapiro

Gulf war illness (GWI) is a chronic multi-symptom disease that afflicts 25–33% of troops that were deployed in the 1990–1991 Gulf War. GWI symptoms include cognitive, behavioral and emotional deficits, as well as migraines and pain. It is possible that exposure to Gulf War agents and prophylactics contributed to the reported symptomology. Pyridostigmine bromide (PB) and permethrin (PER) were given to protect from nerve gas attacks and insect vector born disease, respectively. Previous studies have demonstrated that 10 days of exposure to these chemicals can cause symptoms analogous to those observed in GWI, including impairment of long-term memory in mice. Other studies using this model have shown chronic neuroinflammation, and chronic neuroinflammation can lead to altered nociceptive sensitivity. At 10-weeks after the 10-day PB and PER exposure paradigm, we observed lowered nociceptive threshold on the Von Frey test that was no longer evident at 28 weeks and 38 weeks post-exposure. We further determined that vagus nerve stimulation, initiated at 38 weeks after exposure, restores the lowered nociceptive sensitivity. Therefore, stimulating the vagus nerve appears to influence nociception. Future studies are need to elucidate possible mechanisms of this effect.



中文翻译:

海湾战争药剂溴化吡啶斯的明和苄氯菊酯引起过敏性痛觉,迷走神经刺激后可恢复

海湾战争疾病(GWI)是一种慢性多症状疾病,困扰了1990-1991年海湾战争中部署的部队的25-33%。GWI症状包括认知,行为和情感缺陷,以及偏头痛和疼痛。暴露于海湾战争病原体和预防措施可能导致了所报道的症状。分别使用溴吡啶斯的明(PB)和苄氯菊酯(PER)来预防神经毒气和昆虫媒染所致疾病。先前的研究表明,接触这些化学物质10天会引起类似于GWI中观察到的症状,包括损害小鼠的长期记忆。使用此模型的其他研究表明,慢性神经发炎,并且慢性神经发炎会导致伤害感受敏感性的改变。在10天的PB和PER暴露范式之后的10周,我们观察到Von Frey测试降低了伤害感受性阈值,该阈值在暴露后28周和38周时不再明显。我们进一步确定,在暴露后38周开始迷走神经刺激,可以恢复降低的伤害感受敏感性。因此,刺激迷走神经似乎会影响伤害感受。需要进一步研究阐明这种作用的可能机制。

更新日期:2018-09-29
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