Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.
Acoustic Medical Systems, Savoy, IL, USA.
Neuromodulation. 2022 Jun;25(4):504-510. doi: 10.1111/ner.13531. Epub 2021 Sep 2.
Chronic pain affects 7%-10% of Americans, occurs more frequently and severely in females, and available treatments have been shown to have less efficacy in female patients. Preclinical models addressing sex-specific treatment differences in the treatment of chronic pain have been limited. Here we examine the sex-specific effects of low intensity focused ultrasound (liFUS) in a modified sciatic nerve injury (SNI) model.
A modified SNI performed by ligating the common peroneal nerve (CPN) was used to measure sensory, behavioral pain responses, and nerve conduction studies in female and male rats, following liFUS of the L5 dorsal root ganglion.
Using the same dose of liFUS in females and males of the same weight, CPN latency immediately after treatment was increased for 50 min in females compared to 25 min in males (p < 0.001). Improvements in mechanical pain thresholds after liFUS lasted significantly longer in females (seven days; p < 0.05) compared to males (three days; p < 0.05). In females, there was a significant improvement in depression-like behavior as a result of liFUS (N = 5; p < 0.01); however, because males never developed depression-like behavior there was no change after liFUS treatment.
Neuromodulation with liFUS has a greater effect in female rats on CPN latency, mechanical allodynia duration, and depression-like behavior. In order to customize neuromodulatory techniques for different patient phenotypes, it is essential to understand how they may alter sex-specific pathophysiologies.
慢性疼痛影响了 7%-10%的美国人,女性中更为常见且更为严重,且已证实现有的治疗方法对女性患者的疗效较低。针对慢性疼痛治疗中性别特异性治疗差异的临床前模型一直有限。在此,我们研究了低强度聚焦超声(liFUS)在改良坐骨神经损伤(SNI)模型中的性别特异性作用。
通过结扎腓总神经(CPN)进行改良 SNI,以测量雌性和雄性大鼠的感觉、行为疼痛反应和神经传导研究,之后对 L5 背根神经节进行 liFUS。
在体重相同的雌性和雄性中使用相同剂量的 liFUS,CPN 潜伏期在治疗后立即增加 50 分钟,而雄性则增加 25 分钟(p<0.001)。liFUS 后机械痛阈的改善在雌性中持续时间明显更长(七天;p<0.05),而在雄性中持续时间更短(三天;p<0.05)。liFUS 导致雌性的抑郁样行为有明显改善(N=5;p<0.01);然而,由于雄性从未出现抑郁样行为,因此 liFUS 治疗后没有变化。
liFUS 神经调节对 CPN 潜伏期、机械性痛觉过敏持续时间和抑郁样行为在雌性大鼠中有更大的影响。为了根据不同患者表型定制神经调节技术,了解它们如何改变性别特异性病理生理学至关重要。