Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA.
Mol Pain. 2010 Jan 27;6:7. doi: 10.1186/1744-8069-6-7.
Unilateral constrictive sciatic nerve injury (uCCI) is a common neuropathic pain model. However, the bilateral constrictive injury (bCCI) model is less well studied, and shows unique characteristics. In the present study, we sought to correlate effects of bCCI on nocifensive responses to cold and mechanical stimuli with selected dorsal horn anatomic markers. bCCI or sham ligation of both rat sciatic nerves were followed up to 90 days of behavioural testing. Additional rats sacrificed at 15, 30 and 90 days were used for anatomic analyses. Behavioural tests included hindpaw withdrawal responses to topical acetone, cold plate testing, an operant thermal preference task and hindpaw withdrawal thresholds to mechanical probing.
All nocifensive responses to cold increased and remained enhanced for >45 days. Mechanical withdrawal thresholds decreased for 25 days only. Densitometric analyses of immunoperoxidase staining in the superficial dorsal horn at L4-5 revealed decreased cholecystokinin (CCK) staining at all times after bCCI, decreased mu opiate receptor (MOR) staining, maximal at 15 days, increased neuropeptide Y (NPY) staining only at days 15 and 30, and increased neurokinin-1 receptor (NK-1R) staining at all time points, maximal at 15 days. Correlation analyses at 45 days post-bCCI, were significant for individual rat nocifensive responses in each cold test and CCK and NK-1R, but not for MOR or NPY.
These results confirm the usefulness of cold testing in bCCI rats, a new approach using CCI to model neuropathic pain, and suggest a potential value of studying the roles of dorsal horn CCK and substance P in chronic neuropathic pain. Compared to human subjects with neuropathic pain, responses to cold stimuli in rats with bCCI may be a useful model of neuropathic pain.
单侧缩窄性坐骨神经损伤（uCCI）是一种常见的神经性疼痛模型。然而，双侧缩窄性损伤（bCCI）模型研究较少，表现出独特的特征。在本研究中，我们试图将 bCCI 对冷和机械刺激的伤害性反应与选定的背角解剖学标志物相关联。对双侧大鼠坐骨神经进行 bCCI 或假结扎，并进行了长达 90 天的行为测试。另外，在 15、30 和 90 天处死部分大鼠，用于解剖分析。行为测试包括足底对局部丙酮的退缩反应、冷板测试、操作性热偏好任务以及足底机械探测的退缩阈值。
所有对冷的伤害性反应均增加，并持续增强>45 天。机械退缩阈值仅在 25 天内下降。L4-5 背角浅层的免疫过氧化物酶染色密度分析显示，bCCI 后所有时间点胆囊收缩素（CCK）染色减少，最大在 15 天；阿片μ受体（MOR）染色减少，最大在 15 天；神经肽 Y（NPY）染色仅在 15 天和 30 天增加；神经激肽-1 受体（NK-1R）染色增加，最大在 15 天。bCCI 后 45 天的个体大鼠伤害性反应在每个冷测试中与 CCK 和 NK-1R 呈显著相关，但与 MOR 或 NPY 无关。
这些结果证实了冷测试在 bCCI 大鼠中的有用性，这是一种使用 CCI 来模拟神经性疼痛的新方法，并表明研究背角 CCK 和 P 物质在慢性神经性疼痛中的作用具有潜在价值。与患有神经性疼痛的人类患者相比，bCCI 大鼠对冷刺激的反应可能是神经性疼痛的有用模型。
