Contribution of amygdala CRF neurons to chronic pain.
Contribution of amygdala CRF neurons to chronic pain.
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DOI：
10.1016/j.expneurol.2017.08.010
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Dimitrov E
中科院分区：
文献类型：
--
作者：
Andreoli M;Marketkar T;Dimitrov E
我们研究了杏仁核促肾上腺皮质激素释放因子（CRF）神经元在神经病理性疼痛引起的下行疼痛抑制扰动中的作用。强迫游泳增加了未受伤小鼠的甩尾反应潜伏期，这种现象被称为应激诱导镇痛（SIA），但没有改变坐骨神经收缩引起的神经性疼痛小鼠的甩尾反应潜伏期。神经病理性疼痛还增加中央杏仁核（CeAmy）CRF和脊髓背角ΔFosB的表达。接下来，我们用cre激活的AAV-DREADD（Designer Receptors Exclusively Activated by Designer Drugs）载体注射CRF-cre小鼠的CeAmy。DREADD/Gq激活CRF神经元不影响受损的SIA，但DREADD/Gi抑制CRF神经元可恢复SIA并降低神经病理性疼痛小鼠的异常性疼痛。通过向蓝斑（LC）联合注射逆行cre病毒（CAV 2-cre）和cre激活的腺相关病毒白喉毒素（AAV-FLEX-DTX）病毒（AAV-FLEX-DTX），研究了SIA调控的可能下游通路。病毒注射后，在注射同侧或对侧进行坐骨神经收缩。在神经病理性疼痛小鼠中，切除杏仁核向损伤侧LC的投射而非对侧，可完全恢复SIA，降低异常性疼痛，并降低脊髓中ΔFosB的表达。SIA损伤可能偏向损伤侧，这一点在一项实验中得到了证实，在该实验中，即使在未受伤的小鼠中，单侧抑制LC也会降低SIA。目前疼痛研究领域的观点认为，疼痛的慢性化过程是由下行疼痛抑制功能异常引起的。我们的研究结果表明，持续性疼痛引起的CRF神经元的持续活动导致SIA受损，这是下行疼痛抑制失调的症状。因此，杏仁核CRF神经元的过度激活很可能是疼痛慢性化的一个重要因素。
We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over-activation of amygdala CRF neurons is very likely an important contributing factor for pain chronification.
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影响因子：
7.4
作者：
Hughes SW;Hickey L;Hulse RP;Lumb BM;Pickering AE
通讯作者：
Pickering AE
影响因子：
2.5
作者：
Howorth, Patrick W.;Teschemacher, Anja G.;Pickering, Anthony E.
通讯作者：
Pickering, Anthony E.
影响因子：
2.5
作者：
Marchant, Nathan J.;Densmore, Valerie S.;Osborne, Peregrine B.
通讯作者：
Osborne, Peregrine B.
DOI：
10.1002/cne.23024
发表时间：
2012-06-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Bruinstroop E;Cano G;Vanderhorst VG;Cavalcante JC;Wirth J;Sena-Esteves M;Saper CB
通讯作者：
Saper CB
影响因子：
5.3
作者：
Dimitrov, Eugene L.;Tsuda, Mumeko C.;Usdin, Ted B.
通讯作者：
Usdin, Ted B.