Accepted

Astrocytes are the main cell type responsible for the regulation of brain homeostasis, including the maintenance of ion gradients and neurotransmitter clearance. These processes are tightly coupled to changes in the intracellular sodium (Na) concentration. While activation of the sodium-potassium-ATPase (NKA) in response to an elevation of extracellular K may decrease intracellular Na, the cotransport of transmitters, such as glutamate, together with Na results in an increase in astrocytic Na. This increase in intracellular Na can modulate, for instance, metabolic downstream pathways. Thereby, astrocytes are capable to react on a fast time scale to surrounding neuronal activity intracellular Na fluctuations and adjust energy production to the demand of their environment. Beside the well-documented conventional roles of Na signaling mainly mediated through changes in its electrochemical gradient, several recent studies have identified more atypical roles for Na, including protein interactions leading to changes in their biochemical activity or Na-dependent regulation of gene expression. In this review, we will address both the conventional as well as the atypical functions of astrocytic Na signaling, presenting the role of transporters and channels involved and their implications for physiological processes in the central nervous system (CNS). We will also discuss how these important functions are affected under pathological conditions, including stroke and migraine. We postulate that Na is an essential player not only in the maintenance of homeostatic processes but also as a messenger for the fast communication between neurons and astrocytes, adjusting the functional properties of various cellular interaction partners to the needs of the surrounding network.

Chronic pain is a significant global health issue. For most individuals with chronic pain, biomedical treatments do not provide adequate relief. Given the evidence that neurophysiological abnormalities are associated with pain, it is reasonable to consider treatments that target these factors, such as neurofeedback (NF). The primary objectives of this review were to summarize the current state of knowledge regarding: (1) the different types of NF and NF protocols that have been evaluated for pain management; (2) the evidence supporting each NF type and protocol; (3) if targeted brain activity changes occur with NF training; and (4) if such brain activity change is associated with improvements on treatment outcomes. Inclusion criteria were intentionally broad to encompass every empirical study using NF in relation to pain. We considered all kinds of NF, including both electroencephalogram- (EEG-) and functional magnetic resonance imagining- (fMRI-) based. We searched the following databases from inception through September 2019: Pubmed, Ovid, Embase, Web of Science, PsycINFO. The search strategy consisted of a combination of key terms referring to all NF types and pain conditions (e.g., neurofeedback, rt-fMRI-NF, BOLD, pain, migraine). A total of 6,552 citations were retrieved; 24 of these that were included in the review. Most of the studies were of moderate quality, included a control condition and but did not include a follow-up. They focused on studying pain intensity (83%), pain frequency, and other variables (fatigue, sleep, depression) in samples of adults ( = 7-71) with headaches, fibromyalgia and other pain conditions. Most studies (79%) used EEG-based NF. A wide variety of NF types and protocols have been used for pain management aiming to either increase, decrease or regulate brain activity in certain areas theoretically associated with pain. Given the generally positive results in the studies reviewed, the findings indicate that NF procedures have the potential for reducing pain and improving other related outcomes in individuals with chronic pain. However, the current evidence does not provide definitive conclusions or allow for reliable recommendations on which protocols or methods of administration may be the most effective. These findings support the need for continued – but higher quality – research in this area.

The Strategy for Patient-Oriented Research Chronic Pain Network was founded in 2016 and is a patient-oriented research network funded by the Canadian Institutes of Health Research. The Network incorporates patient partners throughout its governance and operations meaning that patient partners may contribute to research projects in ways that warrant scientific authorship as defined by the International Committee of Medical Journal Editors. The Network did a brief informal review of guidance on patient authorship in 2019, but could not find any practical documentation to guide its members on this topic. Note the term patient partner here refers to a patient (or caregiver or other person with lived experience) who is a partner or collaborator on a research team. This guidance does not address patients as participants in a research study. This guidance has been co-written by a group of researchers and patient partners of the Chronic Pain Network in an effort to address this gap. It is intended for both researchers and patient partner audiences. This guidance is meant to facilitate conversations between researchers and patient partners about authorship and/or acknowledgement regarding research projects on which they collaborate. While the overall principles of academic authorship and acknowledgement remain unchanged, nuances for interpreting these principles through the lens of patient engagement or patient-oriented research is provided. Teams that carry out patient-oriented research projects will require different preparation to empower all team members (researchers and patient partners) to discuss authorship and acknowledgement. To facilitate these conversations, we have included an overview of the scientific publishing process, explanation of some common terms, and sets of considerations are provided for both patient partners and researchers in determining the range of team member contribution from acknowledgement to authorship. Conversations about authorship can be difficult, even for established research teams. This guidance, and the resources discussed within it, are provided with the intention of making these conversations easier and more thoughtful.