Clark Anna K, Gentry Clive, Bradbury Elizabeth J, McMahon Stephen B, Malcangio Marzia
Neurorestoration, Wolfson Centre for Age Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guys Campus, London SE1 1UL, UK.
Eur J Pain. 2007 Feb;11(2):223-30. doi: 10.1016/j.ejpain.2006.02.003. Epub 2006 Mar 20.
Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 h following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA-induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered.
越来越多的证据支持这样一种假说，即脊髓小胶质细胞调节某些慢性疼痛状态的发生和维持。在此，我们研究了外周炎性损伤和外周神经损伤后脊髓小胶质细胞的作用。我们观察到，损伤后2周同侧背角小胶质细胞显著激活，神经损伤后50天以及足底注射酵母聚糖后24小时出现双侧激活，但足底注射完全弗氏佐剂（CFA）后未出现双侧激活。同侧而非对侧小胶质细胞激活与后爪机械性痛觉过敏相关。脊髓注射胶质代谢灭活剂氟代柠檬酸可减轻外周神经损伤后同侧痛觉过敏和双侧脊髓小胶质细胞激活。鞘内注射氟代柠檬酸可逆转足底注射酵母聚糖后的痛觉过敏，但对CFA诱导的痛觉过敏无逆转作用。这些数据表明脊髓胶质细胞在外周神经损伤后机械性痛觉过敏的持续存在中发挥作用。然而，对侧脊髓小胶质细胞的激活与伤害感受无关。此外，小胶质细胞激活的时间进程及其对炎性疼痛的作用似乎取决于所施加的炎性刺激。
