Depletion of Endogenous Noradrenaline Does Not Prevent Spinal Cord Plasticity Following Peripheral Nerve Injury
Depletion of Endogenous Noradrenaline Does Not Prevent Spinal Cord Plasticity Following Peripheral Nerve Injury
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DOI：
10.1016/j.jpain.2011.09.009
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发表时间：
2012-01-01
期刊：
影响因子：
4
通讯作者：
Eisenach, James C.
中科院分区：
文献类型：
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作者：
Hayashida, Ken-ichiro;Peters, Christopher M.;Eisenach, James C.
本研究探讨了内源性去甲肾上腺素对周围神经损伤后大鼠脊髓神经胶质和神经元可塑性的作用。鞘内注射与皂草素（DβH-皂草素）缀合的多巴胺-β-羟化酶抗体完全耗尽脊髓中的去甲肾上腺素能轴突，并且还减少了脑干蓝斑（A6）和A5去甲肾上腺素能核中的去甲肾上腺素能神经元以及室旁核中的去甲肾上腺素能轴突 下丘脑的。 DβH-皂草素治疗本身不会改变机械撤退阈值，但会增强 L5-L6 脊神经结扎后的机械超敏反应和鞘内可乐定镇痛。在脊髓神经结扎大鼠的脊髓背角中，DβH-皂草素治疗增加了胆碱乙酰转移酶免疫反应性以及小胶质细胞中离子钙结合接头分子1[IBA1]的免疫反应性和星形胶质细胞中胶质纤维酸性蛋白的免疫反应性以及脑源性神经生长因子含量。然而，DβH-皂草素治疗并没有改变神经损伤后右美托咪定从末端释放乙酰胆碱的分数。这些结果表明，去甲肾上腺素能纤维的内源性张力对于神经损伤后α2-肾上腺素能受体镇痛和神经胶质激活的可塑性不是必需的，但可能对神经胶质激活起到抑制作用。 观点：本研究表明，内源性去甲肾上腺素调节周围神经损伤后脊髓中胶质和胆碱能神经元的可塑性，从而影响 与神经性疼痛相关的脊髓变化的病理生理学。 (C) 2012 年，美国疼痛协会
The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-beta-hydroxylase antibody conjugated to saporin (D beta H-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. D beta H-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, D beta H-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. D beta H-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of alpha 2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation.Perspective: This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain. (C) 2012 by the American Pain Society