Abstract：
Chronic pain is associated with alterations in fundamental cellular processes. Here, we investigate whether Beclin 1, a protein essential for initiating the cellular process of autophagy, is involved in pain processing and is targetable for pain relief. We find that monoallelic deletion of Becn1 increases inflammation-induced mechanical hypersensitivity in male mice. However, in females, loss of Becn1 does not affect inflammation-induced mechanical hypersensitivity. In males, intrathecal delivery of a Beclin 1 activator, tat-beclin 1, reverses inflammation- and nerve injury-induced mechanical hypersensitivity and prevents mechanical hypersensitivity induced by brain-derived neurotrophic factor (BDNF), a mediator of inflammatory and neuropathic pain. Pain signaling pathways converge on the enhancement of N-methyl-D-aspartate receptors (NMDARs) in spinal dorsal horn neurons. The loss of Becn1 upregulates synaptic NMDAR-mediated currents in dorsal horn neurons from males but not females. We conclude that inhibition of Beclin 1 in the dorsal horn is critical in mediating inflammatory and neuropathic pain signaling pathways in males.
摘要：
慢性疼痛与基本细胞过程的改变有关。这里,我们研究了Beclin1，一种启动细胞自噬过程所必需的蛋白质，参与疼痛处理，可缓解疼痛。我们发现Becn1的单等位基因缺失增加了雄性小鼠的炎症诱导的机械超敏反应。然而,在女性中，Becn1的缺失不影响炎症诱导的机械性超敏反应。在男性中，鞘内递送Beclin1激活剂，tat-beclin1，逆转炎症和神经损伤引起的机械性超敏反应，并防止脑源性神经营养因子（BDNF）引起的机械性超敏反应，炎症和神经性疼痛的介质。疼痛信号通路集中于脊髓背角神经元中N-甲基-D-天冬氨酸受体（NMDARs）的增强。Becn1的丢失上调了雄性而非雌性背角神经元中突触NMDAR介导的电流。我们得出的结论是，背角中Beclin1的抑制对于介导男性炎症和神经性疼痛信号通路至关重要。
