外周传入神经亚型转换参与急性术后痛形成的研究

Postoperative pain remains a challenge because the mechanism is not clear. Peripheral afferent phenotypic switching contributes to algesia and allodynia in neuropathic and inflammatory pain. C and Aδ fibers sense pain and Aβ for touch while Aβ afferents can also participate in pain sensation by switching their phenotype to C or Aδ afferents in some pathologic situation. Meanwhile, the expression and distribution of the acute pain-related mediators in afferents may also change during phenotypic switching, thereby enhancing the synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli. Patients show algesia and allodynia postoperatively, but whether afferents phenotypic switching is involved is unknown. In this study, we investigate whether phenotypic switching contributes to acute postoperative pain. Using the rat incisional pain model, we will study whether Aβ afferents switch the phenotype via electrophysiological single fiber recording. The expression and distribution of acute pain-related mediators in C、Aδ or Aβ fibers, in DRG and dorsal horn of spinal cord are examined using immunohistochemistry, molecular biology. To further confirm the involvement of the mediators, we will test whether inhibition of the mediators will affect the phenotypic switching. We propose that a phenotypic switching occur in peripheral afferents after incision. The acute pain-related mediators can be found in Aβ afferent as well as in C and Aδ afferents. Inhibition of these mediators will block the phenotypic switching and eliminate postoperative pain. This study will be helpful for developing new analgesic therapies for acute postoperative pain management.

术后痛的机制不明导致术后镇痛效果欠佳。外周传入神经亚型转换参与神经病理性及炎性疼痛中痛觉过敏及感觉异常的形成。亚型转换是指感受触觉的Aβ神经表现出感受痛觉的C及Aδ神经电生理特性。同时痛觉相关因子在三种神经的表达发生变化，促进痛觉形成。急性术后痛也有痛觉过敏和感觉异常的临床表现，而是否存在亚型转换尚有待研究。 本课题关注亚型转换参与急性术后痛的形成。将使用大鼠急性术后痛模型，通过电生理、免疫组化、分子生物学及基因沉默等手段观察组织损伤后传入神经电生理特性变化；在传入神经纤维、背根神经节及脊髓背角检测急性痛相关因子及其mRNA在三种传入神经表达的改变；以及抑制上述因子对亚型转换的影响。 我们推测损伤后传入神经电生理特性发生亚型转换；通常表达在C及Aδ神经的急性痛相关因子在Aβ表达增加；抑制其表达可阻断亚型转换而缓解术后痛。本研究有望为术后镇痛新药开发提供理论依据。

术后痛的机制不明导致术后镇痛效果欠佳。外周传入神经亚型转换参与神经病理性及炎性疼痛中痛觉过敏及感觉异常的形成。亚型转换是指感受触觉的Aβ神经表现出感受痛觉的C 及 Aδ的电生理特征。同时痛觉相关因子在三种神经的表达发生变化， 促进痛觉形成。急性术后痛也有痛觉过敏和感觉异常的临床表现，而是否发生亚型转换仍有待研究。 . 我们使用大鼠急性术后痛模型，采用免疫组化、分子生物学及基因敲除等手段观察外周组织损伤后，外周神经系统相关疼痛调节因子的表达变化。研究发现足底切开后在局部肌肉、皮肤、传入神经纤维、背根神经节中NGF、ASIC3、TRPV1及artemin的mRNA 及蛋白质的表达增加；此外，表达上述疼痛因子的细胞类型也发生改变，NGF、artmin在Aβ纤维上表达较对照组增加，而ASIC3及TRPV1在C纤维上的表达较对照组增加，提示NGF、artemin、ASIC3及TRPV1参与了亚型转换；给予相应阻滞剂后其疼痛行为学得到改善，提示上述因子参与急性术后疼痛的调节。. 本研究结果提示足底切开后，外周传入神经系统artemin、NGF等因子也表达在Aβ纤维上，抑制该类因子的表达可阻断亚型转换的发生，上述因子的特异性阻断剂有望成为新型术后镇痛药物。.