An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences
An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences
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DOI：
10.1038/s41593-023-01519-w
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发表时间：
2024-01-03
影响因子：
25
通讯作者：
Wang，Changhe
中科院分区：
文献类型：
--
作者：
Song，Qian;Wei，Anqi;Wang，Changhe
慢性疼痛的中枢机制仍然难以捉摸。在这里，我们确定了一个互惠的神经元电路之间的小鼠前扣带皮层（ACC）和腹侧被盖区（VTA），介导痛觉过敏和异常性疼痛和他们的情绪后果之间的相互恶化，从而慢性神经性疼痛。投射到腹侧被盖区的ACC能神经元（ACCGlu）通过激活局部GABA能中间神经元（VTAGABA）间接抑制多巴胺能神经元（VTADA），并且这种作用在神经损伤后得到加强。VTADA神经元反过来投射到ACC，并与最初的ACCGluneurons形成突触，以传达情绪变化的反馈信息。因此，ACCGlu-VTAGABA-VTADA-ACCGlu正反馈环介导持续性疼痛和共病的焦虑抑郁样行为的进展和维持。在神经性疼痛的小鼠模型中，这种反馈回路的中断缓解了痛觉过敏和焦虑抑郁样行为，无论是急性的还是长期的。
The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADAneurons in turn project to the ACC and synapse to the initial ACCGluneurons to convey feedback information from emotional changes. Thus, an ACCGlu–VTAGABA–VTADA–ACCGlupositive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.