Mor David, Kendig Michael D, Kang James W M, Gemikonakli Gizem, Austin Paul J, Kalman Eszter, Corbit Laura H
Discipline of Biomedical Sciences, School of Medical Sciences, The University of Sydney, NSW 2006, Australia.
School of Psychology, The University of Sydney, NSW 2006, Australia.
Behav Brain Res. 2017 Jun 15;328:123-129. doi: 10.1016/j.bbr.2017.04.003. Epub 2017 Apr 5.
Chronic neuropathic pain often leads to impaired cognition and reduced behavioural flexibility. This study used a rat model to investigate if a peripheral nerve injury, with or without an additional acute psychological stress, alters behavioural flexibility and goal directed behaviour as measured by sensitivity to devaluation. Neuropathic pain was induced by a chronic constriction injury (CCI) of the sciatic nerve. CCI, sham-injury and naïve rats were trained to press two levers for two rewards. In outcome devaluation tests, one of the rewards was devalued by pre-feeding it to satiety, immediately prior to an extinction test measuring responding on the two levers. The ability to preferentially direct responding toward the action earning the currently-valued reward was taken as evidence of goal-directed behaviour. To test the impact of acute stress, rats were subjected to 15min restraint following pre-feeding and prior to the devaluation test. Neither CCI surgery nor acute stress alone altered sensitivity to devaluation, but in combination CCI and acute stress significantly reduced sensitivity to devaluation. This Study demonstrates that relatively mild stressors that are without effect in uninjured populations can markedly impair cognition under conditions of chronic pain. It further suggests that overlapping neural substrates regulated by nerve injury and/or acute stress are having a cumulative effect on behavioural flexibility.
慢性神经性疼痛常导致认知障碍和行为灵活性降低。本研究使用大鼠模型来探究外周神经损伤（无论是否伴有额外的急性心理应激）是否会改变行为灵活性以及通过贬值敏感性测量的目标导向行为。通过坐骨神经慢性压迫损伤（CCI）诱导神经性疼痛。对CCI大鼠、假手术大鼠和未受伤大鼠进行训练，使其按压两个杠杆以获取两种奖励。在结果贬值测试中，在测量对两个杠杆反应的消退测试前，通过预先喂食使其中一种奖励达到饱腹感从而使其贬值。将优先将反应导向获得当前有价值奖励的行为的能力作为目标导向行为的证据。为了测试急性应激的影响，在预先喂食后且在贬值测试前，对大鼠进行15分钟的束缚。单独的CCI手术或急性应激均未改变对贬值的敏感性，但CCI与急性应激相结合则显著降低了对贬值的敏感性。本研究表明，在未受伤群体中无影响的相对轻度应激源在慢性疼痛条件下可显著损害认知。它还进一步表明，由神经损伤和/或急性应激调节的重叠神经基质对行为灵活性具有累积效应。
