Romero-Grimaldi Carmen, Berrocoso Esther, Alba-Delgado Cristina, Madrigal Jose Luis M, Perez-Nievas Beatriz G, Leza Juan Carlos, Mico Juan Antonio
From the Department of Neuroscience, University of Cádiz, Cádiz, Spain; CIBER of Mental Health (CIBERSAM), ISCIII, Madrid, Spain; Nursing Faculty "Salus Infirmorum," University of Cádiz, Cádiz, Spain; Department of Psychology, University of Cádiz, Cádiz, Spain; Faculty Medicine, Department of Neuroscience (Pharmacology and Psychiatry), University of Cádiz, Cádiz, Spain; Faculty Medicine, Department of Pharmacology, University Complutense; and IIS Hospital 12 de Octubre, Madrid, Spain.
Anesth Analg. 2015 Oct;121(4):1078-1088. doi: 10.1213/ANE.0000000000000838.
Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many of these patients also experience stress unrelated to their illness, which can aggravate their symptoms. These nociceptive inputs are received by the hippocampus, in which maladaptive neuroplastic changes may occur in the conditions of chronic pain. The hippocampus is a structure involved in emotionality, learning, and memory, and the proliferating cells in the granular layer of the hippocampal dentate gyrus respond to chronic pain by slowing their turnover. However, whether the maturation, survival, and integration of newborn cells in the hippocampus are affected by chronic pain remains unclear. In addition, it is unknown whether an added stress may increase this effect.
We have evaluated the proliferation, differentiation, and survival of newborn hippocampal cells in a rat model of neuropathic pain (chronic constriction injury), with or without stress (chronic immobilization), by assessing the incorporation of bromodeoxyuridine into proliferating cells and immunostaining.
The data obtained indicated that there was a decrease in the number of proliferating cells 8 days after nerve injury in animals subjected to neuropathic pain, an effect that was exacerbated by stress. Moreover, 4 weeks after nerve injury, neuropathic pain was associated with a loss of neuroblasts and the reduced survival of new mature neurons in the hippocampal granular layer, phenomena that also were increased by stress. By contrast, the rate of differentiation was not affected in this paradigm.
Neuropathic pain negatively influences hippocampal neurogenesis (proliferation and survival), and this effect is exacerbated by stress. These neuroplastic changes may account for the affective and cognitive impairment seen in patients with chronic pain.
慢性疼痛患者常伴有情感障碍和认知衰退，这严重损害了他们的生活质量。此外，这些患者中的许多人还经历与疾病无关的压力，这会加重他们的症状。这些伤害性传入信号由海马体接收，在慢性疼痛状态下，海马体可能会发生适应性不良的神经可塑性变化。海马体是一个与情绪、学习和记忆有关的结构，海马齿状回颗粒层中的增殖细胞通过减缓其更新来应对慢性疼痛。然而，慢性疼痛是否会影响海马体中新生细胞的成熟、存活和整合仍不清楚。此外，额外的压力是否会增强这种影响也尚不清楚。
我们通过评估溴脱氧尿苷掺入增殖细胞的情况和免疫染色，在神经性疼痛（慢性压迫性损伤）大鼠模型中，评估有无压力（慢性束缚）时新生海马细胞的增殖、分化和存活情况。
获得的数据表明，遭受神经性疼痛的动物在神经损伤8天后增殖细胞数量减少，压力会加剧这种影响。此外，在神经损伤4周后，神经性疼痛与海马颗粒层中神经母细胞的丢失和新成熟神经元存活率降低有关，压力也会加剧这些现象。相比之下，在这个模型中分化率不受影响。
神经性疼痛对海马神经发生（增殖和存活）有负面影响，压力会加剧这种影响。这些神经可塑性变化可能解释了慢性疼痛患者出现的情感和认知障碍。
