Ziv-Sefer Sagit, Raber Pnina, Barbash Shahar, Devor Marshall
Dept. Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Pain. 2009 Nov;146(1-2):148-57. doi: 10.1016/j.pain.2009.07.020. Epub 2009 Aug 14.
Do contrasting neuropathic pain diagnoses share common pathophysiological mechanisms? Selective breeding was used to derive rat lines with a common genetic background but a striking difference in the degree of spontaneous pain behavior expressed in the neuroma model of neuropathic pain (HA rats (high autotomy) and LA rats (low autotomy)). The contrasting pain phenotype in these lines is attributable to allelic differences at a small number of genetic loci. Here we show that HA and LA rats also differ in their nocifensive response to applied stimuli in the Chung (spinal nerve ligation, SNL) model of neuropathic pain. This includes tactile allodynia and hyperalgesia, and heat allodynia. The degree of hypersensibility varied with sex, age at the time of nerve injury, and the extent of the nerve lesion. F1 crosses of HA and LA rats and inbred Lewis rats showed low levels of autotomy but variable levels of hypersensibility to applied stimuli. Results indicate that alleles which predispose to spontaneous neuropathic pain also predispose to stimulus-evoked pain (allodynia and hyperalgesia). This, in turn, suggests that despite contrasting etiology and behavioral endpoints, pain phenotype in the neuroma and the SNL models shares common pathophysiological mechanisms.
不同的神经性疼痛诊断是否具有共同的病理生理机制？采用选择性育种方法培育出具有共同遗传背景，但在神经性疼痛的神经瘤模型中表现出的自发疼痛行为程度存在显著差异的大鼠品系（HA大鼠（高自残率）和LA大鼠（低自残率））。这些品系中截然不同的疼痛表型归因于少数基因座上的等位基因差异。在此，我们表明，在神经性疼痛的Chung（脊髓神经结扎，SNL）模型中，HA和LA大鼠对施加刺激的伤害性反应也存在差异。这包括触觉异常性疼痛和痛觉过敏，以及热异常性疼痛。超敏反应的程度随性别、神经损伤时的年龄以及神经损伤的程度而变化。HA大鼠与LA大鼠的杂交F1代以及近交系Lewis大鼠表现出低水平的自残行为，但对施加刺激的超敏反应水平各不相同。结果表明，易引发自发性神经性疼痛的等位基因也易引发刺激诱发的疼痛（异常性疼痛和痛觉过敏）。这进而表明，尽管病因和行为终点不同，但神经瘤模型和SNL模型中的疼痛表型具有共同的病理生理机制。
