Dear readers,
The ability to sense noxious threats (nociception) is an important physiological function of our body. Pain, the conscious percept resulting from nociceptive input and modulating factors, however, can frequently become chronic and lose its protective function, resulting in human suffering. Maladaptive plasticity, triggered by a variety of factors including structural and functional plasticity and psychosocial variables, is currently believed to underlie pain chronicity. A primary goal in the field, therefore, is to elucidate mechanisms mediating the transition between acute, physiological and chronic, pathological pain.
Despite major progress in our understanding of molecular processes and intricate signalling pathways in the neurobiology of nociception, we are far from understanding pain and treating it adequately. A major bottleneck has been the lack of understanding about the nature of neural circuits that determine sensory and emotional components of the highly subjective experience of pain. Moreover, although maladaptive plasticity is established as a leading concept in pain chronicity and it is recognized that neural circuits mediating reward, fear and depression interact with nociceptive circuits in chronic pain patients, the specific nature and the causal role of circuit changes is not understood. The Collaborative Research Center (CRC) 1158 “From nociception to chronic pain: structure-function properties of neural pathways and their reorganization”, funded since 2015 by the Deutsche Forschungsgemeinschaft, aims to deliver an understanding of cells, circuits and networks that impart causality and specificity to pain, examine their modulation by disease processes and psychosocial factors, and elucidate their reorganization in chronic pain.
This special issue endeavours to address some of these critical questions and covers key topics in understanding and treating chronic pain. It contains contributions of members of CRC1158, but also addresses important research outside of the CRC that is relevant to this topic. The review by Enrico Leipold and Carla Nau provides an overview on the sodium channels that are of primary importance in sensing of nociceptive stimuli at primary afferent nerve endings, their mutations associated with major pain disorders and therapeutic opportunities and challenges in employing sodium channel blockers. The article by Stefan Lechner summarizes the latest insights into the diversity and emerging molecular and functional specificity of peripheral afferents and types of spinal neurons they connect with, which serve to segregate diverse modalities of nociception and tactile sensory information. Rohini Kuner reviews molecular mechanisms underlying nociceptive processing at the first synapse in the nociceptive pathway and the accumulating evidence showing that structural and functional plasticity of spinal synapses go hand-in-hand in the transition from acute to chronic pain. Moving further along the nociceptive pathway, the article by Patrik Krieger, Rebecca A. Mease and Alexander Groh reviews our current understanding of thalamocortical gating and modulation of pain, underlining that the thalamus not only serves as a relay centre and filter, but also as an important modulatory venue in shaping pain. The article by Sigrid Elsenbruch reviews how visceral organs sense sensory stimuli and discusses the intricacies of reciprocal communication between the brain and gut, its modulation in states of hypervigilance and how this shapes the highly prevalent problem of visceral pain. Finally, Jamila Andoh and Herta Flor review the latest insights into mechanisms underlying phantom limb pain, critically discuss peripheral and central contributions and outline new perspectives for reversing pain and abnormal perception in patients with phantom limb pain.
We hope that these articles will not only update the neuroscience community on latest insights into pain chronicity, but also highlight that the nociceptive pathway and pain system provide an excellent model for understanding the fundamentals of both function and dysfunction of the nervous system. We are grateful to the Neurowissenschaftliche Gesellschaft and the editorial board of Neuroforum for choosing to highlight this scientifically fascinating and clinically important topic and thank all contributing authors for their dedicated efforts.
With best wishes,
Rohini Kuner
Herta Flor
Article note
German version available under https://doi.org/10.1515/nf-2017-0031
© 2017 by De Gruyter