Dauvergne C, Molet J, Reaux-Le Goazigo A, Mauborgne A, Mélik-Parsadaniantz S, Boucher Y, Pohl M
INSERM UMRS 975, Faculté de Médecine Pitié-Salpêtrière, Paris, France; UFR Odontologie, Université Denis Diderot, Paris, France.
Eur J Pain. 2014 Mar;18(3):360-75. doi: 10.1002/j.1532-2149.2013.00377.x. Epub 2013 Aug 5.
Chemokine (C-C motif) ligand 2 (CCL2) participates in different mechanisms contributing to the spinal cord inflammation and pain development after sciatic nerve injury. Recent data also support its role in orofacial thermal hypersensitivity, although its implication in different phases of trigeminal pain emergence is unclear. We assessed the importance of CCL2 signalling in biochemical and behavioural alterations during the early and late stages following chronic constriction injury of infraorbital nerve (ION-CCI), a model of peripheral traumatic trigeminal pain.
After evaluating the consequences of CCL2 intracisternal injection in naïve rats, we determined the expression changes for CCL2, inflammatory and glia activation markers in the somatosensory trigeminal complex (STC) and trigeminal ganglia (TG) after ION-CCI. The role of CCL2 signalling was assessed using pre-emptive or 'curative' intracisternal treatment with specific CCL2 receptor antagonist - INCB3344.
Exogenous CCL2 evoked spontaneous behaviour reminiscent of orofacial pain and marked mechanical hypersensitivity, associated with increased expression of proinflammatory cytokines and glial markers in STC and TG. CCL2-evoked changes were prevented by the co-administration of INCB3344. Two weeks after ION-CCI, mRNA for CCL2, glial and inflammatory markers were up-regulated, and CCL2-immunoreactivity accumulated in central and ganglionic tissues. At this time, repeated intracisternal administration of INCB3344 did not attenuate the ION-CCI-associated behavioural nor biochemical changes. By contrast, pre-emptive INCB3344 treatment delayed the emergence of trigeminal mechanical allodynia and associated biochemical alterations.
Our data suggest that CCL2 is involved principally in the early events accompanying the ION lesion rather than in long-term alterations and the maintenance of trigeminal mechanical hypersensitivity.
趋化因子（C-C基序）配体2（CCL2）参与了坐骨神经损伤后脊髓炎症和疼痛发展的不同机制。近期数据也支持其在口腔面部热超敏反应中的作用，尽管其在三叉神经痛发生不同阶段的影响尚不清楚。我们评估了CCL2信号在眶下神经慢性压迫损伤（ION-CCI，一种外周创伤性三叉神经痛模型）早期和晚期生化及行为改变中的重要性。
在评估单纯大鼠脑池内注射CCL2的后果后，我们测定了ION-CCI后体感三叉神经复合体（STC）和三叉神经节（TG）中CCL2、炎症和胶质细胞激活标志物的表达变化。使用特异性CCL2受体拮抗剂INCB3344进行脑池内预防性或“治疗性”处理来评估CCL2信号的作用。
外源性CCL2诱发了类似于口腔面部疼痛的自发行为和明显的机械性超敏反应，伴有STC和TG中促炎细胞因子和胶质细胞标志物表达增加。INCB3344共同给药可预防CCL2诱发的变化。ION-CCI两周后，CCL2、胶质细胞和炎症标志物的mRNA上调，CCL2免疫反应性在中枢和神经节组织中积聚。此时，重复脑池内注射INCB3344并未减轻ION-CCI相关的行为或生化变化。相比之下，预防性INCB3344处理延迟了三叉神经机械性异常性疼痛的出现及相关生化改变。
我们的数据表明，CCL2主要参与ION损伤后的早期事件，而非长期改变及三叉神经机械性超敏反应的维持。
