A cardinal, intractable symptom of neuropathic pain is mechanical allodynia, pain caused by innocuous stimuli via low-threshold mechanoreceptors such as Aβ fibers. However, the mechanism by which Aβ fiber-derived signals are converted to pain remains incompletely understood. Here we identify a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP⁺) and show that specific ablation or silencing of AAV-NpyP⁺ SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses. AAV-NpyP⁺ neurons received excitatory inputs from Aβ fibers and transmitted inhibitory GABA signals to lamina I neurons projecting to the brain. In a model of neuropathic pain developed by peripheral nerve injury, AAV-NpyP⁺ neurons exhibited deeper resting membrane potentials, and their excitation by Aβ fibers was impaired. Conversely, chemogenetic activation of AAV-NpyP⁺ neurons in nerve-injured rats reversed Aβ fiber-derived neuropathic pain-like behavior that was shown to be morphine-resistant and reduced pathological neuronal activation of superficial SDH including lamina I. These findings suggest that identified inhibitory SDH interneurons that act as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavioral responses. Thus, enhancing activity of these neurons may offer a novel strategy for treating neuropathic allodynia.

神经性疼痛的主要，难治性症状是机械性异常性疼痛，是由低阈值机械感受器（例如Aβ纤维）无害刺激引起的疼痛。然而，将Aβ纤维来源的信号转化为疼痛的机制仍未完全了解。在这里，我们确定了结合神经肽Y启动子（AAV-NpyP ⁺）的腺相关病毒载体在脊髓背角（SDH）中抑制性中间神经元的子集，并显示了AAV-NpyP ⁺ SDH中神经元的特定消融或沉默转换后的触摸感应Aβ纤维衍生的信号以抵抗吗啡的疼痛样行为反应。AAV-NpyP ⁺神经元从Aβ纤维接收兴奋性输入，并将抑制性GABA信号传递至伸向大脑的层状I神经元。在由周围神经损伤引起的神经性疼痛模型中，AAV-NpyP ⁺神经元表现出更深的静息膜电位，并且它们的Aβ纤维兴奋性受到损害。相反，AAV-NpyP ^+的化学生成激活神经损伤大鼠的神经元逆转了Aβ纤维衍生的神经性疼痛样行为，该行为被证明具有吗啡抗性，并减少了包括层板I在内的浅层SDH的病理神经元活化。将触摸感应Aβ纤维信号转换为类似疼痛的行为反应。因此，增强这些神经元的活性可以提供治疗神经性异常性疼痛的新策略。