A novel animal model of graded neuropathic pain Utility to investigate mechanisms of population heterogeneity
A novel animal model of graded neuropathic pain Utility to investigate mechanisms of population heterogeneity
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DOI：
10.1016/j.jneumeth.2010.08.025
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发表时间：
2010-10-30
影响因子：
3
通讯作者：
Rolan, Paul E.
中科院分区：
文献类型：
--
作者：
Grace, Peter M.;Hutchinson, Mark R.;Rolan, Paul E.
神经病理性疼痛的潜在机制尚未得到很好的理解，导致许多患者的治疗结果不令人满意。动物模型由于其模拟疼痛超敏反应的感知能力而支持了目前对疼痛机制的大部分理解，但是受到其二项式方法的限制（疼痛vs对照）这并不能反映伤害性超敏反应的临床异质性。坐骨神经铬肠线每只Sprague道利大鼠接受4片铬肠线以控制肠线引起的炎症。处理组为神经元缝合线（N）皮下缝合线（S）NOSO NOS 4 N1 S3 N2 S2和N4S 0在术后（PO）第29天，神经周缝合线的数量和vonFrey阈值之间存在剂量-反应关系（N 0 S4 <N1 S3 <N2 S2 <N4 S 0 P < 0 0 5）采用该分级模型检测大鼠腰段脊髓背角胶质细胞活化标志物表达。（P <0 0 5 r（2）> 0 9），并与背外侧索相关（DLF P = 010 r（2）> 08），术后14天，星形胶质细胞GFAP表达与同侧背角的异常性疼痛分级呈正相关（P = 0 18 r（2）> 0 6）和同侧DLF（P <0 0 5 r（2）> 0 9）DLF胶质细胞活化可能是对侧疼痛的贡献者我们的新型分级模型具有动态范围，允许灵敏地检测相互作用和对神经病理性疼痛处理的微妙影响（C）2010 Elsevier B V版权所有
The mechanisms underlying neuropathic pain are not well understood resulting in unsatisfactory treatment outcomes for many patients Animal models underpin much of the current understanding of pain mechanisms due to their perceived ability to mimic pain hypersensitivities however are limited by their binomial approach (pain vs control) which does not reflect the clinical heterogeneity in nociceptive hypersensitivity We modified the chronic constriction injury model by varying the number of sciatic nerve chromic gut sutures Each Sprague Dawley rat received 4 pieces of chromic gut to control for the inflammatory challenge posed by the gut Treatment groups were neuronal sutures (N) subcutaneous sutures (S) NOSO N0S4 N1S3 N2S2 and N4S0 At postoperative (PO) day 29 there was a dose-response relationship between the number of perineural sutures and von Frey thresh old (N0S4 < N1S3 < N2S2 < N4S0 P < 0 05) This graded model was applied to investigate lumbar dorsal spinal cord glial activation marker expression Microglial CD1 1b expression was positively correlated with graded allodynia in the ipsilateral dorsal horn (P < 005 r(2) > 0 9) and associated in the dorsolateral funiculus (DLF P = 010 r(2) > 0 8) at PO day 14 Astrocyte GFAP expression was positively associated with graded allodynia in the ipsilateral dorsal horn (P = 0 18 r(2) > 0 6) and ipsilateral DLF (P < 005 r(2) > 0 9) DLF glial activation may represent a contributor to contralateral pain Our novel graded model has a dynamic range allowing sensitive detection of interactions and subtle influences on neuropathic pain processing (C) 2010 Elsevier B V All rights reserved