PDF(Pubmed)
Abstract：
Pain is a multidimensional experience of sensory-discriminative, cognitive, and affective processes; however, current basic research methods rely heavily on response to threshold stimuli, bypassing the supraspinal processing that ultimately gives rise to the pain experience. We developed the operant plantar thermal assay (OPTA), which utilizes a novel, conflict-based operant task requiring evaluation and active decision-making to obtain reward under thermally aversive conditions to quantify thermal pain tolerance. In baseline measures, male and female mice exhibited similar temperature preferences, however in the OPTA, female mice exhibited greater temperature-dependent tolerance, as defined by choice time spent in an adverse thermal condition to obtain reward. Increasing reward salience (4% vs 10% sucrose solution) led to increased thermal tolerance for males but not females. To determine whether neuropathic and inflammatory pain models alter thermal tolerance, animals with chronic constriction injury (CCI) or complete Freund\'s adjuvant (CFA), respectively, were tested in the OPTA. Surprisingly, neuropathic animals exhibited increased thermal tolerance, as shown by greater time spent in the reward zone in an adverse thermal condition, compared with sham animals. There was no effect of inflammation on thermal tolerance. Administration of clonidine in the CCI model led to increased thermal tolerance in both injured and sham animals. In contrast, the non-steroidal anti-inflammatory meloxicam was anti-hyperalgesic in the CFA model, but reduced thermal pain tolerance. These data support the feasibility of using the OPTA to assess thermal pain tolerance to gain new insights into complex pain behaviors and to investigate novel aspects of analgesic efficacy.
摘要：
疼痛是一种多维度的感觉辨别体验，认知，和情感过程；然而，当前的基本研究方法严重依赖于对阈值刺激的反应，绕过脊柱上处理，最终导致疼痛体验。我们开发了操作性足底热测定(OPTA)，它利用了一部小说，基于冲突的操作任务，需要评估和积极决策，以在热厌恶条件下获得奖励，以量化热疼痛耐受性。在基线度量中，雄性和雌性小鼠表现出相似的温度偏好，然而在OPTA,雌性小鼠表现出更高的温度依赖性耐受性，根据在不利的热条件下花费的选择时间来获得奖励。奖励显着性的增加（4％对10％蔗糖溶液）导致男性而非女性的耐热性增加。为了确定神经性和炎性疼痛模型是否改变热耐受性，患有慢性收缩损伤（CCI）或完全弗氏佐剂（CFA）的动物，分别,在OPTA中进行了测试。令人惊讶的是,神经病动物表现出增加的耐热性，如在不利的热条件下在奖励区中花费的更多时间所示，与假动物相比。炎症对热耐受性没有影响。在CCI模型中施用可乐定导致受伤和假动物的热耐受性增加。相比之下,非甾体抗炎美洛昔康在CFA模型中具有抗痛觉过敏作用，但热疼痛耐受性降低。这些数据支持使用OPTA评估热痛耐受性以获得对复杂疼痛行为的新见解并研究镇痛功效的新方面的可行性。
