Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, Frankfurter Strasse 100, 35392 Giessen, Germany.
Center for Mind, Brain and Behavior (CMBB), Philipps University Marburg & Justus Liebig University Giessen, 35032 Marburg, Germany.
Int J Mol Sci. 2022 Oct 28;23(21):13124. doi: 10.3390/ijms232113124.
Inflammatory processes within the peripheral nervous system (PNS) are associated with symptoms of hyperalgesia and allodynia. Pro-inflammatory mediators, such as cytokines or prostaglandins, modulate the excitability of nociceptive neurons, called peripheral sensitization. Here, we aimed to examine if previously reported effects of in vitro stimulation with lipopolysaccharide (LPS) on primary cell cultures of dorsal root ganglia (DRG) reflect changes in a model of LPS-induced systemic inflammation in vivo. Male rats were intraperitoneally injected with LPS (100 µg/kg) or saline. Effects of systemic inflammation on expression of inflammatory mediators, neuronal Ca responses, and activation of inflammatory transcription factors in DRG were assessed. Systemic inflammation was accompanied by an enhanced expression of pro-inflammatory cytokines and cyclooxygenase-2 in lumbar DRG. In DRG primary cultures obtained from LPS-treated rats enhanced neuronal capsaicin-responses were detectable. Moreover, we found an increased activation of inflammatory transcription factors in cultured macrophages and neurons after an in vivo LPS challenge compared to saline controls. Overall, our study emphasizes the role of inflammatory processes in the PNS that may be involved in sickness-behavior-associated hyperalgesia induced by systemic LPS treatment. Moreover, we present DRG primary cultures as tools to study inflammatory processes on a cellular level, not only in vitro but also ex vivo.
外周神经系统（PNS）中的炎症过程与痛觉过敏和感觉异常的症状有关。促炎介质，如细胞因子或前列腺素，调节伤害感受神经元的兴奋性，称为外周致敏。在这里，我们旨在研究体外用脂多糖（LPS）刺激对背根神经节（DRG）原代细胞培养物的先前报道的影响是否反映了体内 LPS 诱导的全身炎症模型中的变化。雄性大鼠经腹腔注射 LPS（100µg/kg）或盐水。评估全身炎症对 DRG 中炎症介质表达、神经元钙反应和炎症转录因子激活的影响。全身炎症伴随着腰 DRG 中促炎细胞因子和环氧化酶-2 的表达增强。在来自 LPS 处理大鼠的 DRG 原代培养物中，可检测到辣椒素反应增强的神经元。此外，与盐水对照相比，我们发现体内 LPS 挑战后培养的巨噬细胞和神经元中炎症转录因子的激活增加。总体而言，我们的研究强调了 PNS 中炎症过程的作用，这些过程可能与全身 LPS 治疗引起的疾病相关的痛觉过敏有关。此外，我们提出 DRG 原代培养物作为研究细胞水平炎症过程的工具，不仅在体外，而且在离体。
