Department of Neurology, University of Hamburg (UKE), Germany NeuroImage Nord, Department of Systems Neuroscience, University of Hamburg (UKE), Germany Department of Human Biology, University of Hamburg, Germany Oxford Centre for Functional MRI on the Brain, Department of Clinical Neurology & Nuffield Department of Anaesthetics, Oxford University, John Radcliffe Hospital, Oxford, UK Hamburg University of Applied Sciences, Germany.
Pain. 2010 Mar;148(3):503-508. doi: 10.1016/j.pain.2009.12.014. Epub 2010 Jan 22.
Habituation to repetitive painful stimulation may represent an important protection mechanism against the development of chronic pain states. However, the exact neurobiological mechanisms of this phenomenon remain unclear. In this study we (i) explore the somatotopic specificity of pain attenuation over time and (ii) investigate the role of the endogenous opioid system in its development. We investigated 24 healthy volunteers with a paradigm of daily painful stimulation of the left volar forearm for 1 week. Habituation was assessed by comparing pain-related responses (ratings and thresholds) between days 1 and 8. To test whether a repetition-dependent attenuation of pain is restricted to the site of stimulus application or induces additional systemic effects indicative of a central mechanism, we also measured pain-related responses at the contralateral arm and the left leg. To assess the role of the endogenous opioid system in this mechanism, we used the opioid-receptor antagonist naloxone in a double-blind design. Repetitive painful stimulation over several days resulted in a significant habituation to pain at the site of daily stimulation. In addition, we also observed significant pain attenuation at the non-stimulated limbs. This effect was less pronounced at the untreated arm compared to the treated arm and even weaker in the leg, displaying a significant Stimulation-Site x Time interaction. The development of pain habituation was unaffected by the opioid antagonist naloxone. Taken together, these results strongly support the role of central components in the mechanism of pain habituation that do not directly involve the endogenous opioid system.
习惯化是指对重复的疼痛刺激逐渐适应，这种现象可能是预防慢性疼痛状态的一种重要保护机制。然而，其确切的神经生物学机制仍不清楚。在本研究中，我们（i）探讨了随时间推移疼痛减轻的躯体定位特异性，以及（ii）研究了内源性阿片系统在其发展中的作用。我们对 24 名健康志愿者进行了为期一周的左侧掌侧前臂重复疼痛刺激的研究。通过比较第 1 天和第 8 天的疼痛相关反应（评分和阈值）来评估习惯化。为了测试重复依赖性的疼痛减轻是否仅限于刺激应用部位，还是会引起其他表明中枢机制的全身性效应，我们还测量了对侧手臂和左侧腿部的疼痛相关反应。为了评估内源性阿片系统在这种机制中的作用，我们在双盲设计中使用了阿片受体拮抗剂纳洛酮。几天的重复疼痛刺激导致在每日刺激部位出现明显的疼痛习惯化。此外，我们还观察到非刺激肢体的疼痛明显减轻。与治疗部位相比，未治疗部位的这种效应不那么明显，与治疗部位相比，腿部的效应甚至更弱，表现出明显的刺激部位与时间的相互作用。阿片拮抗剂纳洛酮对疼痛习惯化的发展没有影响。总之，这些结果强烈支持了疼痛习惯化机制中的中枢成分的作用，这些成分并不直接涉及内源性阿片系统。
