Knerlich-Lukoschus Friederike, Juraschek Mathias, Blömer Ulrike, Lucius Ralph, Mehdorn Hubertus M, Held-Feindt Janka
Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany.
J Neurotrauma. 2008 May;25(5):427-48. doi: 10.1089/neu.2007.0431.
Spinal cord injury (SCI) often results in intractable chronic central pain syndromes. Recently chemokines such as CCL2 were identified as possible key integrators of neuropathic pain and inflammation after peripheral nerve lesion. The focus of the current study was the investigation of time-dependent CCL2 and CCR2 expression in relation to central neuropathic pain development after spinal cord impact lesions of 100, 150, or 200 kdyn force on spinal cord level T9 in adult rats. Below-level pain was monitored with weekly sensory testing for 42 days after SCI. In parallel expression of CCL2/CCR2 on cervical, thoracic, and lumbar levels was investigated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry early (7 days [7d]), intermediate (15d), and late (42d) after lesion. Cellular source and anatomical pain related expression was determined by double-immunohistochemistry. Force-defined SCI led to acute mechanical hypersensitivity in all lesion groups, and to persistent below-level pain in severely injured animals. While in the early post-operative time course, CCL2 and CCR2 were expressed in astroglia and granulocytes only on level T9; there was additional astroglial CCL2 expression in dorsal columns and dorsal horns above and below T9 of severely injured animals 42d after lesion. In dorsal horns (level L3-L5) of animals exhibiting chronic below-level pain CCL2 was co-expressed with transmitters and receptors that are involved in nociceptive processing like calcitonin gene-related peptide (CGRP), Substance-P, vanilloid-receptor-1, and its activated phosphorylated form. These data demonstrate lesion grade dependence of below-level pain development and suggest chemokines as potential candidates for integrating inflammation and central neuropathic pain after SCI.
脊髓损伤（SCI）常导致难以治疗的慢性中枢性疼痛综合征。最近，诸如CCL2等趋化因子被确定为周围神经损伤后神经性疼痛和炎症的可能关键整合因子。本研究的重点是调查成年大鼠T9脊髓水平受到100、150或200千达因力的脊髓撞击损伤后，CCL2和CCR2表达随时间的变化与中枢神经性疼痛发展的关系。脊髓损伤后42天，每周进行一次感觉测试以监测损伤平面以下的疼痛情况。同时，通过实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，在损伤后早期（7天[7d]）、中期（15d）和晚期（42d），研究CCL2/CCR2在颈、胸和腰段水平上的表达情况。通过双重免疫组织化学确定细胞来源和与解剖学疼痛相关的表达。不同力度的脊髓损伤导致所有损伤组均出现急性机械性超敏反应，在严重受伤的动物中出现持续的损伤平面以下疼痛。在术后早期，CCL2和CCR2仅在T9水平的星形胶质细胞和粒细胞中表达；损伤后42天，在严重受伤动物的T9上方和下方的背柱和背角中，星形胶质细胞额外表达CCL2。在表现出慢性损伤平面以下疼痛的动物的背角（L3-L5水平），CCL2与参与伤害性处理的递质和受体如降钙素基因相关肽（CGRP）、P物质、香草酸受体-1及其活化的磷酸化形式共同表达。这些数据表明损伤平面以下疼痛发展与损伤程度相关，并提示趋化因子可能是脊髓损伤后整合炎症和中枢神经性疼痛的潜在候选因素。
