Elevated substance-P-like immunoreactivity levels in spinal dialysates during the formalin test in normal and diabetic rats
Elevated substance-P-like immunoreactivity levels in spinal dialysates during the formalin test in normal and diabetic rats
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DOI：
10.1016/s0006-8993(99)02345-8
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发表时间：
2000-02-21
期刊：
影响因子：
2.9
通讯作者：
Malmberg, AB
中科院分区：
文献类型：
--
作者：
Calcutt, NA;Stiller, CO;Malmberg, AB
药理学研究表明，在福尔马林试验期间，P物质参与脊髓伤害性处理。然而，没有直接测量的时间变化的P物质水平在脊髓内的清醒动物的报告。此外，P物质水平和福尔马林诱发的伤害性行为之间的分离可能存在于糖尿病大鼠中，因为夸大的痛觉过敏行为与周围神经P物质水平降低共存。本研究进行了直接测量的外观P物质样免疫反应（SP-LI）在脊髓CSF清醒，不受限制的大鼠使用微透析技术注射福尔马林到后爪。还测定了糖尿病对脊髓CSF透析液中福尔马林诱发的SP-LI水平的影响。对照组大鼠脊髓透析液中SP-LI在注射福尔马林后升高，注射后20-30 min达最高，为基础值的325%（p < 0.02）。糖尿病小鼠脊髓根部SP-LI降低（p < 0.05），而脊髓CSF基础水平与对照组无差异。在糖尿病大鼠中，福尔马林诱发的伤害反应行为增加，但在爪福尔马林注射后脊髓CSF透析液中的SP-LI水平显著减弱（p < 0.05），最大值仅为基础水平的161%。这伴随着福尔马林注射部位肿胀减弱和热反应延迟增加。虽然脊髓CSF中SP-LI的增加与福尔马林试验中的2期行为一致，并且在此期间地图有助于脊髓伤害性处理，但过度的脊髓P物质释放不太可能是糖尿病大鼠中观察到的增加的伤害性行为的基础。(C)2000 Elsevier Science B. V.保留所有权利。
Pharmacologic studies implicate the involvement of substance P in spinal nociceptive processing during the formalin test. However, no direct measurement of the temporal changes in substance P levels within the spinal cord of conscious animals has been reported. Further, dissociation between substance P levels and formalin-evoked nocifensive behavior may exist in diabetic rats, as exaggerated hyperalgesic behavior coexists with reduced peripheral nerve substance P levels. The present study was performed to directly measure the appearance of substance-P-like immunoreactivity (SP-LI) in spinal CSF of conscious, unrestrained rats using microdialysis techniques following injection of formalin into the hindpaw. The effect of diabetes upon formalin-evoked SP-LI levels in spinal CSF dialysates was also determined. In control rats, SP-LI increased in spinal dialysates following formalin injection and levels were maximal 20-30 min after injection, rising to 325% of basal values (p < 0.02). Diabetic mts exhibited reduced (p < 0.05) SP-LI in their spinal roots, while basal levels in spinal CSF were not different from controls. Formalin-evoked nocifensive behavior was increased in diabetic rats but SP-LI levels in spinal CSF dialysates after paw formalin injection were significantly (p < 0.05) attenuated, reaching a maximum of only 161% of basal levels. This was accompanied by attenuated swelling at the formalin injection site and increased thermal response latencies. While increased SP-LI in spinal CSF coincides with phase 2 behavior in the formalin test and map contribute to spinal nociceptive processing during this period, exaggerated spinal substance P release is unlikely to underlie the increased nocifensive behavior seen in diabetic rats. (C) 2000 Elsevier Science B.V. All rights reserved.