Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain.
Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain.
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DOI：
10.1097/j.pain.0000000000002224
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发表时间：
2021-08-01
期刊：
影响因子：
7.4
通讯作者：
Kato F
中科院分区：
文献类型：
--
作者：
Sugimoto M;Takahashi Y;Sugimura YK;Tokunaga R;Yajima M;Kato F
补充数字内容在文本中可用。右侧中央杏仁核中γ-氨基丁酸能神经元的活性决定口面炎症大鼠双侧后肢异位机械性异常性疼痛。广泛或异位致敏是慢性疼痛的标志性症状，其特征在于远离原始损伤或炎症部位的多个身体区域的疼痛敏感性异常增强。引起广泛敏感化的核心机制仍然不明。杏仁核的中央核（也称为中央杏仁核，CeA）非常适合发挥这一作用，因为它接收来自不同身体部位的伤害性信息，并调节身体各区域的疼痛敏感性。在这项研究中，我们研究了CeA在大鼠异位致敏的新模型中的作用。将福尔马林注射到雄性Wistar大鼠的左上唇中导致后爪的潜伏性双侧致敏作用持续>13天。γ-氨基丁酸能神经元的化学发生抑制或降钙素基因相关肽受体的阻断在右侧CeA，但不是在左侧，显着减弱这种敏化。此外，化学发生性兴奋的γ-氨基丁酸能神经元在右侧CeA诱导从头双侧后爪致敏大鼠无炎症。这些结果表明，CeA神经元的活动决定后爪触觉敏感性在大鼠与远程炎性疼痛。他们还表明，在大量临床前研究中使用的后爪致敏可能不仅仅是损伤部位疼痛的标志，而是身体任何部位的炎症/疼痛或其他脑区活动导致的CeA活性增强的表现，其具有促进防御/保护行为以避免进一步身体损伤的积极作用。
Supplemental Digital Content is Available in the Text. Activity of gamma-aminobutyric acid-ergic neurons in the right-side central amygdala determines ectopic mechanical allodynia in the bilateral hind limbs in rats with orofacial inflammation. Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma–aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.
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影响因子：
3.3
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通讯作者：
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