Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Chronic pain, with a prevalence of 20–30 % is the major cause of human suffering worldwide, because effective, specific and safe therapies have yet to be developed. It is unevenly distributed among sexes, with women experiencing more pain and suffering. Chronic pain can be anatomically and phenomenologically dissected into three separable but interacting pathways, a lateral ‘painfulness’ pathway, a medial ‘suffering’ pathway and a descending pain inhibitory pathway. One may have pain(fullness) without suffering and suffering without pain(fullness). Pain sensation leads to suffering via a cognitive, emotional and autonomic processing, and is expressed as anger, fear, frustration, anxiety and depression. The medial pathway overlaps with the salience and stress networks, explaining that behavioural relevance or meaning determines the suffering associated with painfulness. Genetic and epigenetic influences trigger chronic neuroinflammatory changes which are involved in transitioning from acute to chronic pain. Based on the concept of the Bayesian brain, pain (and suffering) can be regarded as the consequence of an imbalance between the two ascending and the descending pain inhibitory pathways under control of the reward system. The therapeutic clinical implications of this simple pain model are obvious. After categorizing the working mechanisms of each of the available treatments (pain killers, psychopharmacology, psychotherapy, neuromodulation, psychosurgery, spinal cord stimulation) to 1 or more of the 3 pathways, a rational combination can be proposed of activating the descending pain inhibitory pathway in combination with inhibition of the medial and lateral pathway, so as to rebalance the pain (and suffering) pathways.

疼痛是一种与实际或潜在组织损伤相关的不愉快的感觉和情绪体验。流行率为 20-30% 的慢性疼痛是全世界人类痛苦的主要原因，因为尚未开发出有效、特异和安全的疗法。它在性别之间分布不均，女性经历更多的痛苦和折磨。慢性疼痛可以从解剖学和现象学上分为三个可分离但相互作用的通路，即外侧“疼痛”通路、内侧“痛苦”通路和下行疼痛抑制通路。一个人可以有痛（饱）而不苦，也可以有苦而无痛（饱）。痛觉通过认知、情绪和自主神经处理导致痛苦，并表现为愤怒、恐惧、沮丧、焦虑和抑郁。中间通路与显着性和压力网络重叠，解释了行为相关性或意义决定了与痛苦相关的痛苦。遗传和表观遗传影响引发慢性神经炎症变化，这些变化涉及从急性疼痛到慢性疼痛的转变。基于贝叶斯大脑的概念，疼痛（和痛苦）可以被视为奖励系统控制下的两个上行和下行疼痛抑制途径之间不平衡的结果。这种简单疼痛模型的治疗临床意义是显而易见的。在将每种可用治疗（止痛药、精神药理学、心理治疗、神经调节、心理外科、脊髓刺激）的工作机制归类为 3 种途径中的一种或多种后，