Department of Integrative Biology and Pharmacology, McGovern Medical School at UTHealth, Houston, TX, United States.
Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Pain. 2019 Nov;160(11):2440-2455. doi: 10.1097/j.pain.0000000000001642.
Studies using rodent models of neuropathic pain use sham surgery control procedures that cause deep tissue damage. Sham surgeries would thus be expected to induce potentially long-lasting postsurgical pain, but little evidence for such pain has been reported. Operant tests of voluntary behavior can reveal negative motivational and cognitive aspects of pain that may provide sensitive tools for detecting pain-related alterations. In a previously described operant mechanical conflict test involving lengthy familiarization and training, rodents freely choose to either escape from a brightly lit chamber by crossing sharp probes or refuse to cross. Here, we describe a brief (2-day) mechanical conflict protocol that exploits rats' innate exploratory response to a novel environment to detect persistently enhanced pain-avoidance behavior after sham surgeries for 2 neural injury models: thoracic spinal cord injury and chronic constriction injury of the sciatic nerve. Pitting the combined motivations to avoid the bright light and to explore the novel device against pain from crossing noxious probes disclosed a conflicting, hyperalgesia-related reluctance to repeatedly cross the probes after injury. Rats receiving standard sham surgeries demonstrated enhanced pain-like avoidance behavior compared with naive controls, and this behavior was similar to that of corresponding chronic constriction injury or spinal cord injury rats weeks or months after injury. In the case of sham surgery for spinal cord injury, video analysis of voluntary exploratory behavior directed at the probes revealed enhanced forepaw withdrawal responses. These findings have important implications for preclinical investigations into behavioral alterations and physiological mechanisms associated with postsurgical and neuropathic pain.
使用神经病理性疼痛啮齿动物模型的研究采用假手术对照程序，该程序会导致深部组织损伤。因此，假手术预计会引起潜在的长期术后疼痛，但很少有报道表明存在这种疼痛。操作性行为测试可以揭示疼痛的负面动机和认知方面，这可能为检测与疼痛相关的改变提供敏感的工具。在之前描述的涉及长时间熟悉和训练的操作性机械冲突测试中，啮齿动物可以自由选择通过尖锐探针逃离明亮的房间，或者拒绝穿越。在这里，我们描述了一个简短的（2 天）机械冲突协议，该协议利用大鼠对新环境的天生探索反应来检测 2 种神经损伤模型（胸段脊髓损伤和坐骨神经慢性缩窄损伤）后的假手术后持续增强的疼痛回避行为。将避免明亮光线和探索新设备的综合动机与穿过有害探针的疼痛相权衡，揭示了一种冲突性、与痛觉过敏相关的不情愿，即在受伤后反复穿过探针。与未受伤的对照相比，接受标准假手术的大鼠表现出增强的疼痛回避行为，这种行为与相应的慢性缩窄损伤或脊髓损伤大鼠在受伤数周或数月后的行为相似。在脊髓损伤的假手术情况下，对探针的自愿探索行为的视频分析显示出增强的前爪撤回反应。这些发现对术后和神经病理性疼痛相关的行为改变和生理机制的临床前研究具有重要意义。
