糖尿病神经病理性疼痛大鼠脑异常活动的功能磁共振研究
Abnormal activity of brain detected by functional magnetic resonance imaging in a rat model of diabetic neuropathic pain
目的 构建糖尿病神经病理性疼痛大鼠模型，利用功能磁共振成像技术，观察脑功能活动变化情况，探索异常功能活动的脑区。 方法 雄性SD大鼠48只，随机分为糖尿病组（n=36）和对照组（n=12）。糖尿病组通过腹腔注射60 mg/kg链脲佐菌素构建糖尿病模型，同时测定50％机械刺激缩足反射阈值的变化情况，根据触觉诱发性疼痛标准，糖尿病组大鼠被分成疼痛组及无痛组。利用锰离子增强功能磁共振成像技术进行大鼠脑功能成像，图像后处理分析糖尿病神经病理性疼痛大鼠脑内异常功能活动区域。 结果 成功构建糖尿病神经病理性疼痛大鼠模型，发现脑内存在显著性功能活动增强的区域，包括感觉皮层、腹内侧前额叶皮层、前扣带皮层、下橄榄核、梨状皮层、杏仁核及岛叶部分皮层。 结论 糖尿病神经病理性疼痛大鼠脑内部分脑区具有异常功能活动的表现，这些脑区很有可能参与该疼痛调控的中枢机制。
Objective To construct the diabetic neuropathic pain rat model. To detect the functional activity changes of brain and explore the brain regions with abnormal function activities using functional magnetic resonance imaging. Methods Forty-eight male SD rats were chosen and randomly divided into two groups: a diabetes group (n=36) and a control group (n=12). Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg) with observation of the changes of fasting blood glucose level and body weight. Behavioral testing for paw 50% withdrawal threshold was performed at the same time. Tactile allodynia was defined as a 50% withdrawal threshold of less than or equal to 2.0 g. According to the tactile allodynia, the diabetes group was sorted into two groups: the pain group and painless group. Functional activity mapping of brain by manganese enhanced magnetic resonance imaging and voxel-wise t-test were then applied to statistically analyze the brain regions with abnormal function activities in diabetic neuropathic pain rat. Results Diabetic neuropathic pain rat was successfully induced. some brain regions, including the somatosensory cortex, ventromedial prefrontal cortex, anterior cingulate cortex, inferior olive, piriform cortex,and part of the cortexes of the amygdala and insula, were found with significantly enhanced activity in diabetic neuropathic pain rat. Conclusions The results suggest these brain regions with abnormal function activities probably take part in the regulation of diabetic neuropathic pain within central nervous system.
糖尿病 / 疼痛 / 功能磁共振成像 / 异常功能活动 / 大脑
Diabetes / Pain / Functional magnetic resonance imaging / Abnormal function activity / Brain
[1] Peltier A, Goutman SA, Callaghan BC. Painful diabetic neuropathy[J]. BmJ, 2014, 348: g1799.
[2] Albers JW, Pop-Busui R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes[J]. Curr Neurol Neurosci Rep, 2014, 14(8): 473.
[3] Pop-Busui R, Herman WH, Feldman EL, et al. DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history[J]. Curr Diab Rep, 2010, 10(4): 276-282.
[4] Paulson PE, Wiley JW, Morrow TJ. Concurrent activation of the somatosensory forebrain and deactivation of periaqueductal gray associated with diabetes- induced neuropathic pain[J]. Exp Neurol, 2007, 208(2): 305-313.
[5] Cauda F, Sacco K, Duca S, et al. Altered resting state in diabetic neuropathic pain[J]. PLoS One, 2009, 4(2): e4542.
[6] Fischer TZ, Tan AM, Waxman SG. Thalamic neuron hyperexcitability and enlarged receptive fields in the STZ model of diabetic pain[J]. Brain Res, 2009, 1268: 154-161.
[7] Islam MS. Animal models of diabetic neuropathy: progress since 1960s[J]. J Diabetes Res, 2013, 2013: 149452.
[8] Dhuria RS, Singh G, Kaur A, et al. Current status and patent prospective of animal models in diabetic research[J]. Adv Biomed Res. 2015 ,29;4:117.
[9] Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw[J]. J Neurosci Methods,1994,53(1):55-63.
[10] Bock NA, Paiva FF, Silva AC. Fractionated manganese-enhanced MRI[J]. NMR Biomed, 2008, 21(5): 473-478.
[11] Johnson GA, Calabrese E, Badea A, et al. A multidimensional magnetic resonance histology atlas of the Wistar rat brain[J]. Neuroimage, 2012, 62(3): 1848-1856.
[12] Peyron R. Functional brain imaging: what has it brought to our understanding of neuropathic pain? A special focus on allodynic pain mechanisms[J]. Pain, 2016, 157: S67-71.
[13] Mao J, Mayer DJ, Price DD. Patterns of increased brain activity indicative of pain in a rat model of peripheral mononeuropathy[J]. J Neurosci, 1993, 13(6): 2689-2702.
[14] Lin CS, Hsieh JC, Yeh TC, et al. Functional dissociation within insular cortex: the effect of pre-stimulus anxiety on pain[J]. Brain Res, 2013, 1493: 40-47.
[15] Tseng MT, Chiang MC, Chao CC, et al. fMRI evidence of degeneration-induced neuropathic pain in diabetes: Enhanced limbic and striatal activations[J]. Hum Brain Mapp, 2013, 34(10): 2733-2746.
[16] Tracey I. Nociceptive processing in the human brain[J]. Curr Opin Neurobiol, 2005, 15(4): 478-487.
[17] Schweinhardt P, Bushnell MC. Pain imaging in health and disease-how far have we come[J]? J Clin Invest, 2010, 120(11): 3788-3797.
国家自然科学基金（31300921）；广东省自然科学基金（S2013040016710）；广东省科技计划项目基金(2014A020212179)
京ICP备08002354号-3/
| 〈 |
|
〉 |
