Microglia can modulate spinal nociceptive transmission. Yet, their role in spinal cord stimulation (SCS)-induced pain inhibition is unclear. Here, we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury (CCI) of the sciatic nerve. Male rats received conventional SCS (50 Hz, 80% motor threshold, 180 min, 2 sessions/day) or sham stimulation on days 18–20 post-CCI. SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns. SCS also upregulated the mRNAs of M1-like markers, but not M2-like markers. Inducible NOS protein expression was increased, but brain-derived neurotrophic factor was decreased after SCS. Intrathecal minocycline (1 μg–100 μg), which inhibits microglial activation, dose-dependently attenuated the mechanical hypersensitivity. Pretreatment with low-dose minocycline (1 μg, 30 min) prolonged the SCS-induced pain inhibition. These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.

小胶质细胞可以调节脊髓伤害性传递。然而，它们在脊髓刺激 (SCS) 诱导的疼痛抑制中的作用尚不清楚。在这里，我们研究了 SCS 如何影响坐骨神经慢性收缩性损伤 (CCI) 大鼠腰脊髓中的小胶质细胞活化。雄性大鼠在 CCI 后第 18-20 天接受常规 SCS（50 Hz，80% 运动阈值，180 分钟，2 次/天）或假刺激。SCS 暂时减弱了同侧后爪的机械超敏反应，并增加了双侧背角的 OX-42 免疫反应性。SCS 还上调 M1 样标记物的 mRNA，但不上调 M2 样标记物的 mRNA。SCS 后诱导型 NOS 蛋白表达增加，但脑源性神经营养因子减少。鞘内注射米诺环素 (1 μg–100 μg)，可抑制小胶质细胞活化，剂量依赖性地减弱机械超敏反应。用低剂量米诺环素（1 μg，30 分钟）预处理可延长 SCS 诱导的疼痛抑制。这些发现表明，传统的 SCS 可能会自相矛盾地增加脊髓 M1 样小胶质细胞的活动，从而损害其自身抑制疼痛的能力。