School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Mol Pain. 2020 Jan-Dec;16:1744806920971914. doi: 10.1177/1744806920971914.
Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24-32 months) versus young mice (2-4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.
临床上，疼痛在整个生命周期中的发生率不均匀，对老年人的影响更大。相比之下，病理性疼痛的临床前模型通常使用幼鼠或年轻成年动物来突出神经胶质细胞、促炎细胞因子和趋化因子在脊髓背角病理性信号发生和维持中的作用。这种不匹配的潜在影响也因日益认识到，由于促炎细胞因子/趋化因子信号和神经胶质细胞激活增强，衰老的中枢神经系统处于慢性炎症状态而变得复杂。为了解决这个问题，我们研究了衰老对与神经性疼痛、神经胶质信号、神经传递和神经炎症相关的基因表达的影响。我们使用 qRT-PCR 来定量基因表达，并集中研究脊髓背角，因为这是神经性疼痛的一个重要扰动部位。为了控制基因表达的全局与区域特异性与年龄相关的变化，我们检查了脊髓的腹侧半部分。我们的结果表明，与年轻小鼠（2-4 个月）相比，老年（24-32 个月）小鼠的促炎趋化因子、模式识别受体和神经递质系统成分的表达显著改变。值得注意的是，这些变化的幅度和方向取决于脊髓区域。例如，趋化因子 Cxcl13 在背侧脊髓中的表达增加了 119 倍，但在老年和年轻小鼠的腹侧脊髓中仅增加了 2 倍。因此，我们提出，老年动物的背侧脊髓存在区域特异性改变，为病理性疼痛的发展提供了条件，而这些变化可能在没有通常与这些疾病相关的外周触发因素的情况下发生。
