Alan Edwards Centre for Research on Pain and Faculty of Dentistry, McGill University, Montreal, Quebec, Canada ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
PLoS One. 2013 Nov 13;8(11):e80766. doi: 10.1371/journal.pone.0080766. eCollection 2013.
Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.
基于动物研究和一些间接的临床证据，多巴胺被认为具有抗伤害感受的作用。在这里，我们直接研究了增加和减少细胞外多巴胺可用性对健康志愿者疼痛感知的影响。在研究 1 中，参与者分别在不同的时段服用安慰剂和低剂量的中枢作用 D2 受体拮抗剂舒必利，旨在通过主要的突触前阻断来增加突触多巴胺。热痛阈、耐痛和时间总和没有变化。研究 2 使用急性苯丙氨酸和酪氨酸耗竭（APTD）方法来短暂降低多巴胺的可用性。在一个疗程中，参与者摄入一种会耗尽多巴胺氨基酸前体苯丙氨酸和酪氨酸的混合物。在另一个疗程中，他们摄入营养均衡的对照混合物。APTD 导致在进行不愉快的热刺激后出现轻微的情绪低落反应，但对冷、热或疼痛刺激的感知没有影响。在这两项研究中，多巴胺能神经传递的实验操作都是成功的，这可以通过操作检查来证明。研究结果与多巴胺在急性实验性疼痛中有直接抗伤害感受作用的假说相矛盾。基于多巴胺在奖励处理中的众所周知的作用，我们假设在疼痛的情况下，多巴胺作用于刺激的显著性，并可能在回避行为的启动中发挥作用，而不是在急性实验性疼痛中有直接的抗伤害感受作用。
