Evidence for a distinct neuro-immune signature in rats that develop behavioural disability after nerve injury.
Evidence for a distinct neuro-immune signature in rats that develop behavioural disability after nerve injury.
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DOI：
10.1186/s12974-015-0318-4
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发表时间：
2015-05-20
影响因子：
9.3
通讯作者：
Keay KA
中科院分区：
文献类型：
--
作者：
Austin PJ;Berglund AM;Siu S;Fiore NT;Gerke-Duncan MB;Ollerenshaw SL;Leigh SJ;Kunjan PA;Kang JW;Keay KA
慢性神经性疼痛是一种神经免疫障碍，其特征在于异常性疼痛、痛觉过敏和自发性疼痛，以及使人衰弱的情感动机障碍（例如，社交活动减少、睡眠-觉醒周期中断、快感缺乏和抑郁）。免疫系统在神经损伤后感觉改变中的作用已被充分证明。然而，它在情感动机障碍的发展中的作用在很大程度上仍然未知。在这里，我们的目的是观察神经性疼痛和残疾大鼠模型外周和脊髓部位免疫反应的变化。62只大鼠接受坐骨神经慢性压迫性损伤（CCI），并根据感觉阈值测试和CCI后居民-入侵者相互作用中优势行为的变化，将其表征为疼痛和残疾、疼痛和短暂残疾或疼痛。CCI后第6天，对神经超微结构进行评估，并对损伤部位的T淋巴细胞和巨噬细胞数量进行定量。在背根神经节（DRG）中定量ATF 3表达。使用多重测定，在坐骨神经、DRG和脊髓中定量八种细胞因子。所有CCI大鼠表现出相同水平的机械性异常性疼痛，结构性神经损伤和重组。所有CCI大鼠的损伤部位和背根神经节均有明显的巨噬细胞和T淋巴细胞浸润。疼痛和残疾大鼠的T淋巴细胞数量显着增加。CCI增加坐骨神经中的IL-6和MCP-1。残疾亚组的检查显示IL-6和MCP-1的增加仅限于疼痛和残疾大鼠。相反，CCI导致IL-17减少，这仅限于疼痛和短暂残疾以及仅疼痛大鼠。CCI显著增加DRG中的IL-6和MCP-1，其中IL-6仅限于疼痛和残疾大鼠。CCI大鼠脊髓中IL-1β、IL-6和MCP-1水平升高。在亚组中，仅疼痛和残疾大鼠的IL-1β升高。本研究确定了CCI后大鼠外周和脊髓部位免疫应答的个体差异。这些变化与残疾程度有关。我们的数据表明，个体免疫特征在神经损伤后的不同行为轨迹中起着重要作用，在某些情况下可能导致持续的情感动机障碍。
Chronic neuropathic pain is a neuro-immune disorder, characterised by allodynia, hyperalgesia and spontaneous pain, as well as debilitating affective-motivational disturbances (e.g., reduced social interactions, sleep-wake cycle disruption, anhedonia, and depression). The role of the immune system in altered sensation following nerve injury is well documented. However, its role in the development of affective-motivational disturbances remains largely unknown. Here, we aimed to characterise changes in the immune response at peripheral and spinal sites in a rat model of neuropathic pain and disability. Sixty-two rats underwent sciatic nerve chronic constriction injury (CCI) and were characterised as either Pain and disability, Pain and transient disability or Pain alone on the basis of sensory threshold testing and changes in post-CCI dominance behaviour in resident-intruder interactions. Nerve ultrastructure was assessed and the number of T lymphocytes and macrophages were quantified at the site of injury on day six post-CCI. ATF3 expression was quantified in the dorsal root ganglia (DRG). Using a multiplex assay, eight cytokines were quantified in the sciatic nerve, DRG and spinal cord. All CCI rats displayed equal levels of mechanical allodynia, structural nerve damage, and reorganisation. All CCI rats had significant infiltration of macrophages and T lymphocytes to both the injury site and the DRG. Pain and disability rats had significantly greater numbers of T lymphocytes. CCI increased IL-6 and MCP-1 in the sciatic nerve. Examination of disability subgroups revealed increases in IL-6 and MCP-1 were restricted to Pain and disability rats. Conversely, CCI led to a decrease in IL-17, which was restricted to Pain and transient disability and Pain alone rats. CCI significantly increased IL-6 and MCP-1 in the DRG, with IL-6 restricted to Pain and disability rats. CCI rats had increased IL-1β, IL-6 and MCP-1 in the spinal cord. Amongst subgroups, only Pain and disability rats had increased IL-1β. This study has defined individual differences in the immune response at peripheral and spinal sites following CCI in rats. These changes correlated with the degree of disability. Our data suggest that individual immune signatures play a significant role in the different behavioural trajectories following nerve injury, and in some cases may lead to persistent affective-motivational disturbances.