Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
CogNAC Research Group, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
Eur J Pain. 2022 Apr;26(4):911-928. doi: 10.1002/ejp.1921. Epub 2022 Feb 16.
Chronic primary low back pain may be associated with hyperalgesia in uninjured tissues and with decreased pain inhibition. Previous studies have shown that the amygdala is involved in pain regulation and chronic pain, that neuronal activity in the amygdala is altered in models of persistent pain, and that the central nucleus of the right amygdala plays an active role in widespread hypersensitivity to noxious stimuli.
Behavioral, electrophysiological, biochemical, and chemogenetic methods were used to examine the role of the central nucleus of the right amygdala in hypersensitivity to noxious stimuli in a rat model of chronic back pain induced by a local injection of Complete Freund Adjuvant (CFA) in paraspinal muscles.
CFA produced chronic inflammation limited to the injected area. CFA-treated rats showed increased pain-like (liking) behaviors during the formalin test compared with controls. They also showed widespread mechanical hypersensitivity compared with controls, which persisted for 2 months. This widespread hypersensitivity was accompanied by altered activity of different types of right amygdala neurons, as shown by extracellular recordings. Plasmatic levels of IL-1β, IL-6, and TNF-α were not elevated after 1 or 2 months, indicating that persistent widespread hypersensitivity is not caused by persistent systemic inflammation. However, chemogenetic inhibition of GABAergic neurons in the right amygdala attenuated widespread mechanical hypersensitivity.
These findings indicate that chronic widespread mechanical hypersensitivity in a model of chronic back pain can be attenuated by inhibiting GABAergic neurons of the right amygdala, and that widespread hypersensitivity is not maintained by chronic systemic inflammation.
The amygdala is a key structure involved in pain perception and modulation. The present results indicate that the GABAergic neurons of its central nucleus are involved in widespread hypersensitivity to noxious stimuli in a rat model of chronic back pain. The inhibition of amygdala GABAergic neurons may be a potential target for future interventions in patients with chronic back pain.
慢性原发性腰痛可能与未受伤组织的痛觉过敏和疼痛抑制减弱有关。先前的研究表明，杏仁核参与疼痛调节和慢性疼痛，持续性疼痛模型中杏仁核神经元活动发生改变，右杏仁核中央核在广泛的伤害性刺激过敏中发挥积极作用。
使用行为学、电生理学、生物化学和化学遗传方法，研究右侧杏仁核中央核在完全弗氏佐剂（CFA）局部注射于脊柱旁肌肉引起的慢性腰痛大鼠模型中对伤害性刺激过敏中的作用。
CFA 导致局限于注射部位的慢性炎症。与对照组相比，CFA 处理的大鼠在福尔马林测试中表现出更多的疼痛样（喜好）行为。与对照组相比，它们还表现出广泛的机械性超敏反应，这种超敏反应持续了 2 个月。这种广泛的超敏反应伴随着不同类型的右杏仁核神经元活动的改变，这通过细胞外记录显示出来。1 或 2 个月后，IL-1β、IL-6 和 TNF-α 的血浆水平没有升高，表明持续的广泛超敏反应不是由持续的全身炎症引起的。然而，右杏仁核 GABA 能神经元的化学遗传抑制减轻了广泛的机械性超敏反应。
这些发现表明，慢性腰痛模型中广泛的机械性超敏反应可通过抑制右侧杏仁核的 GABA 能神经元来减轻，而广泛的超敏反应不受慢性全身性炎症的维持。
杏仁核是参与疼痛感知和调节的关键结构。本研究结果表明，其中央核的 GABA 能神经元参与了慢性腰痛大鼠模型中广泛的伤害性刺激过敏。抑制杏仁核 GABA 能神经元可能是慢性腰痛患者未来干预的一个潜在靶点。
