Navratilova Edita, Porreca Frank
Department of Pharmacology, University of Arizona Health Science Center, Tucson, Arizona, USA.
Nat Neurosci. 2014 Oct;17(10):1304-12. doi: 10.1038/nn.3811. Epub 2014 Sep 25.
Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain.
疼痛本质上是令人不快的，这一特性通过促进动机和学习来保护机体。缓解包括疼痛在内的厌恶状态是有益的。疼痛的厌恶性以及疼痛缓解带来的奖赏，均由大脑奖赏/动机中脑皮质边缘回路编码。在本综述中，我们描述了从临床前模型和人类神经影像学中获得的关于急性和慢性疼痛对奖赏/动机回路影响的当前知识。我们强调了新出现的临床证据，表明这些回路中的解剖学和功能变化促成了从急性疼痛到慢性疼痛的转变。我们提出，评估这些保守回路中的活动可为临床前镇痛疗效评估提供新的结果指标，以改善转化并加速药物发现。我们进一步表明，针对奖赏/动机回路可能为使慢性疼痛对大脑的影响正常化提供一条途径，超越症状管理以促进从慢性疼痛中恢复。
