A spinoparabrachial circuit defined by Tacr1 expression drives pain.
A spinoparabrachial circuit defined by Tacr1 expression drives pain.
复制标题
由Tacr1表达定义的脊髓臂旁回路驱动疼痛。
DOI：
10.7554/elife.61135
复制
发表时间：
2021-02-16
期刊：
影响因子：
7.7
通讯作者：
Chesler A
中科院分区：
文献类型：
--
作者：
Barik A;Sathyamurthy A;Thompson J;Seltzer M;Levine A;Chesler A
疼痛刺激会引起各种感觉、负面情绪和行为的混合。这些无数的效应被认为是由平行的上升回路组合工作产生的。在这里，我们描述了一个从脊髓到大脑的持续疼痛的途径。在没有伤害性输入的情况下，表达Tacr 1的脊髓神经元的子集的激活唤起了躯体定向疼痛相关行为的完整剧目。Tacr 1投射神经元（表达NKR 1）靶向上级臂旁外侧核（PBN-SL）中的一小簇神经元。我们发现，这些神经元，也表达Tacr 1（PBN-SLTacr 1），是响应持续的，但不是急性伤害性刺激。单独激活PBN-SLTacr 1神经元不会引发疼痛反应，而是显著提高疼痛反应行为并抑制瘙痒。值得注意的是，PBN-SLTacr 1神经元沉默的小鼠忽略了长期的伤害性刺激。总之，这些数据揭示了关于这种脊髓臂旁通路及其在持续疼痛感觉中的关键作用的新细节。
Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here, we describe a pathway from spinal cord to brain for ongoing pain. Activation of a subset of spinal neurons expressing Tacr1 evokes a full repertoire of somatotopically directed pain-related behaviors in the absence of noxious input. Tacr1 projection neurons (expressing NKR1) target a tiny cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL). We show that these neurons, which also express Tacr1 (PBN-SLTacr1), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SLTacr1 neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 neurons ignored long-lasting noxious stimuli. Together, these data reveal new details about this spinoparabrachial pathway and its key role in the sensation of ongoing pain.