School of Medical Sciences (Anatomy and Histology), The University of Sydney, NSW 2006, Australia.
J Chem Neuroanat. 2011 Apr;41(3):158-69. doi: 10.1016/j.jchemneu.2011.01.004. Epub 2011 Feb 1.
Complex behavioural disabilities, as well as pain, characterise neuropathic pain conditions for which clinical treatment is sought. In rats, chronic constriction injury (CCI) of the sciatic nerve evokes, allodynia and hyperalgesia as well as three distinct patterns of disability, characterised by changes in social and sleep-wake behaviours: (i) Pain & Disability; (ii) Pain & Transient Disability and (iii) Pain alone. Importantly, the degree of allodynia and hyperalgesia is identical for each of these groups. Social-interactions and sleep-wake behaviours are regulated by neural networks, which converge on the periaqueductal grey (PAG). Rats with Pain & Disability show astrocyte activation restricted to the lateral and ventrolateral PAG. Reactive astrocytes are a hallmark of cell death (apoptosis and necrosis). Quantitative real-time RT-PCR for the mRNAs encoding Bax, Bcl-2, heat shock protein 60 (HSP60), mitogen activated kinase kinase (MEK2) and iNOS was performed on the dorsal midbrains of individual, disability characterised rats, extending our earlier Gene-Chip data, showing a select up-regulation of Bax and MEK2 mRNA, and a down-regulation of HSP60 mRNA, in Pain & Disability rats. The anatomical location of TUNEL and cleaved-caspase-3 immunoreactive profiles in the midbrain was also identified. Rats with Pain & Disability showed: (i) pro-apoptotic ratios of Bax:Bcl-2 mRNAs; (ii) decreased HSP60 mRNA; (iii) increased iNOS and MEK2 mRNAs; (iv) TUNEL-positive profiles in the lateral and ventrolateral PAG; and (v) caspase-3 immunoreactive neurons in the mesencephalic nucleus of the trigeminal nerve. Cell death in these specific midbrain regions may underlie the disabilities characterising this subgroup of nerve-injured rats.
复杂的行为障碍以及疼痛是神经病理性疼痛的特征，这些疼痛需要进行临床治疗。在大鼠中，坐骨神经慢性缩窄性损伤（CCI）会引起痛觉过敏和痛觉超敏，以及三种不同类型的残疾，其特征是社交和睡眠-觉醒行为的变化：（i）疼痛和残疾；（ii）疼痛和短暂残疾；（iii）仅疼痛。重要的是，这些组别的痛觉过敏和痛觉超敏程度是相同的。社交互动和睡眠-觉醒行为受神经网络调节，这些神经网络汇聚在导水管周围灰质（PAG）。有疼痛和残疾的大鼠显示出局限于外侧和腹外侧 PAG 的星形胶质细胞激活。反应性星形胶质细胞是细胞死亡（凋亡和坏死）的标志。对个体残疾大鼠的背侧中脑进行 Bax、Bcl-2、热休克蛋白 60 (HSP60)、丝裂原激活蛋白激酶激酶 (MEK2) 和 iNOS 的 mRNA 进行定量实时 RT-PCR，扩展了我们早期的基因芯片数据，显示 Bax 和 MEK2 mRNA 的选择性上调，以及 HSP60 mRNA 的下调，在疼痛和残疾大鼠中。还确定了中脑 TUNEL 和裂解 caspase-3 免疫反应性谱的解剖位置。疼痛和残疾大鼠表现出：（i） Bax:Bcl-2 mRNA 的促凋亡比例；（ii）HSP60 mRNA 减少；（iii）iNOS 和 MEK2 mRNA 增加；（iv）外侧和腹外侧 PAG 中的 TUNEL 阳性谱；和（v）三叉神经中脑核中的 caspase-3 免疫反应性神经元。这些特定中脑区域的细胞死亡可能是导致这组神经损伤大鼠残疾的原因。
