Farrokhfar Samaneh, Tiraihi Taki, Movahedin Mansoureh, Azizi Hossein
Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Anatomical Sciences, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.
Mol Neurobiol. 2025 Feb;62(2):1620-1630. doi: 10.1007/s12035-024-04350-x. Epub 2024 Jul 16.
Spinal cord injury (SCI) is a sensory-motor injury. Today, combined treatments such as cell therapy along with drug therapy and their interactions are of interest. Morphine is an opioid drug used to relieve intolerable pain. This study aims to evaluate the impact of an antinociceptive dose of morphine (with minimal tolerance/dependence but effective pain relief) on cell therapy in SCI. The antinociceptive dose of morphine was determined in rats with SCI through the Hargreaves and naloxone-induced morphine withdrawal tests. The rats were then allocated to 5 groups: laminectomy, SCI, SCI + Morphine, SCI + cell therapy, SCI + Morphine + cell therapy. The antinociceptive dose (5 mg/kg) was administered on days 1, 4, 10, and 13 (i.p.) post-SCI. On day 7, Neural-like stem cells derived from adipose tissue were transplanted intraspinally into the injured animals, and they were monitored for 12 weeks. The outcomes were assessed using the BBB test, somatosensory evoked potential (SSEP), and histology. The BBB test indicated that morphine significantly hindered functional recovery post-cell transplantation compared to animals receiving only cell therapy (p < 0.05). In the SSEP test, the analysis of amplitude and latency of waves did not reveal a significant difference (p > 0.05). The histological results showed that cell therapy reduced the cavity size post-SCI, while morphine had no significant impact on it. Morphine at the antinociceptive dose significantly impairs motor recovery despite cell therapy. Nonetheless, there was no significant difference between groups in terms of sensory pathway outcomes.
脊髓损伤（SCI）是一种感觉运动损伤。如今，细胞疗法与药物疗法相结合的联合治疗及其相互作用备受关注。吗啡是一种用于缓解难以忍受的疼痛的阿片类药物。本研究旨在评估抗伤害感受剂量的吗啡（耐受性/依赖性最小但能有效缓解疼痛）对脊髓损伤细胞治疗的影响。通过哈格里夫斯试验和纳洛酮诱导的吗啡戒断试验在脊髓损伤大鼠中确定吗啡的抗伤害感受剂量。然后将大鼠分为5组：椎板切除术组、脊髓损伤组、脊髓损伤+吗啡组、脊髓损伤+细胞治疗组、脊髓损伤+吗啡+细胞治疗组。在脊髓损伤后的第1、4、10和13天腹腔注射抗伤害感受剂量（5mg/kg）的吗啡。在第7天，将源自脂肪组织的神经样干细胞经椎管内移植到受伤动物体内，并对它们进行12周的监测。使用BBB测试、体感诱发电位（SSEP）和组织学评估结果。BBB测试表明，与仅接受细胞治疗的动物相比，吗啡显著阻碍了细胞移植后的功能恢复（p<0.05）。在SSEP测试中，波幅和潜伏期的分析未显示出显著差异（p>0.05）。组织学结果表明，细胞治疗减小了脊髓损伤后的空洞大小，而吗啡对此没有显著影响。尽管进行了细胞治疗，但抗伤害感受剂量的吗啡显著损害了运动恢复。尽管如此，各组在感觉通路结果方面没有显著差异。
