Rolf Degen summarizing... The brain circuit for pain is different from that for suffering, and the latter adds the bite to the former, and to other kinds of disorder

The anatomy of pain and suffering in the brain and its clinical implications. Dirk De Ridder, Divya Adhia, Sven Vanneste. Neuroscience & Biobehavioral Reviews, August 16 2021 https://doi.org/10.1016/j.neubiorev.2021.08.013

Highlights

• Acute pain is a symptom of acute or potential tissue damage, chronic pain extends beyond the period of healing of the original insult or injury, and hence lacks the acute warning function of physiological nociception.

• 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.

• In chronic pain the descending pain inhibitory pathway is less activated.

• Pain sensation leads to suffering via a cognitive (insula), emotional (ACC) and autonomic (ACC plus insula) processing, and is expressed as anger, fear, frustration, anxiety and depression, leading to changes in behaviour and functional disability.

• Acute pain transitions into chronic pain under influence of genetic and epigenetic factors.

• The genetic and epigenetic factors modulate neuroinflammation, which is involved in peripheral and central sensitization.

• Chronic pain, with a prevalence of 20-30% is the major cause of human suffering worldwide.

• Perceived pain disability correlates highly with suffering, little with painfulness

• Unpleasantness (and suffering) is transmitted via a phylogenetically old unmyelinated C-fibre network, linked to survival and procreation.

• Pain and suffering depend on salience and context: sadomasochistic erotic behaviour is a clear example.

• The medial pathway overlaps with the salience and stress networks, explaining that behavioural relevance or meaning determines the suffering associated with painfulness.

• Suffering explains the common neurocircuitry of many psychiatric and neurological disorders.

• Women perceive more intense acute and chronic pain and experience more unpleasantness than men.

• Women suffer more than men as evidenced by higher anxiety and depression prevalence.

• The sex-differences in pain perception are genetically encoded and dependent on immunological and hormonal modulation of pain processing.

• The (predictive) Bayesian Brain hypothesis proposes that pain (and suffering) is the consequence of an imbalance between the ascending and descending pain inhibitory pathways. This balance is theorized to be under control of the reward system.

• By 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 pathways in combination with inhibition of the medial and lateral pathway, so as to rebalance the pain (and suffering) pathways.

Abstract: 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 pathways in combination with inhibition of the medial and lateral pathway, so as to rebalance the pain (and suffering) pathways.

Keywords: painacutechroniccognitiveemotionalautonomicanterior cingulate cortex