Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern, Switzerland.
Department of Ophthalmology, Canton Hospital of Lucerne, Switzerland.
Brain. 2018 Jan 1;141(1):63-71. doi: 10.1093/brain/awx289.
See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory interneurons in the spinal cord use glycine and GABA for fast inhibitory neurotransmission. While there is abundant research on these inhibitory pain pathways in animal models, their relevance in humans remains unclear, largely due to the limited possibility to manipulate selectively these pathways in humans. Hyperekplexia is a rare human disease that is caused by loss-of-function mutations in genes encoding for glycine receptors and glycine transporters. In the present study, we tested whether hyperekplexia patients display altered pain perception or central pain modulation compared with healthy subjects. Seven patients with genetically and clinically confirmed hyperekplexia were compared to 14 healthy age- and sex-matched controls. The following quantitative sensory tests were performed: pressure pain detection threshold (primary outcome), ice water tolerance, single and repeated electrical pain detection thresholds, nociceptive withdrawal reflex threshold, and conditioned pain modulation. Statistical analysis was performed using linear mixed models. Hyperekplexia patients displayed lower pain thresholds than healthy controls for all of the quantitative sensory tests [mean (standard deviation)]: pressure pain detection threshold [273 (170) versus 475 (115) kPa, P = 0.003], ice water tolerance [49.2 (36.5) versus 85.7 (35.0) s, P = 0.015], electrical single pain detection threshold [5.42 (2.64) versus 7.47 (2.62) mA, P = 0.012], electrical repeated pain detection threshold [3.76 (1.41) versus 5.8 (1.73) mA, P = 0.003], and nociceptive withdrawal reflex [7.42 (3.63) versus 14.1 (6.9) mA, P = 0.015]. Conditioned pain modulation was significantly reduced in hyperekplexia [increase to baseline: 53.2 (63.7) versus 105 (57) kPa, P = 0.030]. Our data demonstrate increased pain sensitivity and impaired central pain modulation in hyperekplexia patients, supporting the importance of glycinergic neurotransmission for central pain modulation in humans.
请参阅 Dickenson 的文章（doi:10.1093/brain/awx334）以获取对此文章的科学评论。脊髓中的抑制性中间神经元使用甘氨酸和 GABA 进行快速抑制性神经传递。虽然在动物模型中对这些抑制性疼痛途径进行了大量研究，但它们在人类中的相关性仍不清楚，主要是因为在人类中选择性地操纵这些途径的可能性有限。发作性肌张力障碍是一种罕见的人类疾病，由编码甘氨酸受体和甘氨酸转运体的基因突变引起。在本研究中，我们测试了发作性肌张力障碍患者与健康受试者相比是否表现出改变的疼痛感知或中枢疼痛调节。将 7 名经基因和临床证实的发作性肌张力障碍患者与 14 名年龄和性别匹配的健康对照组进行比较。进行了以下定量感觉测试：压痛觉检测阈值（主要结局）、冰水耐受力、单次和重复电痛觉检测阈值、伤害性撤回反射阈值和条件性疼痛调制。使用线性混合模型进行统计分析。发作性肌张力障碍患者在所有定量感觉测试中的疼痛阈值均低于健康对照组[平均值（标准差）]：压痛觉检测阈值[273（170）与 475（115）kPa，P=0.003]、冰水耐受力[49.2（36.5）与 85.7（35.0）s，P=0.015]、单次电痛觉检测阈值[5.42（2.64）与 7.47（2.62）mA，P=0.012]、重复电痛觉检测阈值[3.76（1.41）与 5.8（1.73）mA，P=0.003]和伤害性撤回反射阈值[7.42（3.63）与 14.1（6.9）mA，P=0.015]。发作性肌张力障碍患者的条件性疼痛调制明显降低[增加至基线：53.2（63.7）与 105（57）kPa，P=0.030]。我们的数据表明发作性肌张力障碍患者的疼痛敏感性增加和中枢疼痛调节受损，支持甘氨酸能神经传递对人类中枢疼痛调节的重要性。
