Accepted

Migraine is a heterogeneous disorder with variable symptoms and responsiveness to therapy. Due to previous analytic shortcomings, variance in migraine symptoms has been inconsistently related to brain function. In the current analysis we used data from two sites (n=143, male and female humans), and performed Canonical Correlation Analysis (CCA), relating resting-state functional connectivity (RSFC) with a broad range of migraine symptoms ranging from headache characteristics to sleep abnormalities. This identified three dimensions of covariance between symptoms and RSFC. The first dimension related to headache intensity, headache frequency, pain catastrophizing, affect, sleep disturbances, and somatic abnormalities, and was associated with frontoparietal and dorsal attention network connectivity, both of which are major cognitive networks. Additionally, RSFC scores from this dimension – both the baseline value and the change from baseline to post-intervention – were associated with responsiveness to mind-body therapy. The second dimension was related to an inverse association between pain and anxiety, and to default mode network connectivity. The final dimension was related to pain catastrophizing, and salience, sensorimotor and default mode network connectivity. In addition to performing CCA, we evaluated the current clustering of migraine patients into episodic and chronic subtypes, and found no evidence to support this clustering. However, when using RSFC scores from the three significant dimensions, we identified a novel clustering of migraine patients into four biotypes with unique functional connectivity patterns. These findings provide new insight into individual variability in migraine, and could serve as the foundation for novel therapies that take advantage of migraine heterogeneity.Using a large multi-site dataset of migraine patients we identified three dimensions of multivariate association between symptoms and functional connectivity. This analysis revealed neural networks that relate to all measured symptoms, but also to specific symptom ensembles, such as patient propensity to catastrophize painful events. Using these three dimensions, we found four biotypes of migraine informed by clinical and neural variation together. Such findings pave the way for precision medicine therapy for migraine.

For pediatric chronic pain patients, intensive interdisciplinary pain treatment (IIPT) is a well-established treatment. The treatment's short-term effectiveness can be improved by an additive psychosocial aftercare (PAC). However, neither the program's long-term effectiveness nor the patients in particular need have been investigated yet.

Migraine is a chronic headache disease, which ranks second in years lost due to disability. However, the mechanism of migraines is still not clear. In migraine patients, fasting can trigger headache attacks. We explored the probable mechanism of why fasting can induce headaches. Nitroglycerin (NTG) was used to induce acute migraine attacks in mice. Primary astrocytes were used to study the pathophysiological mechanism and a Seahorse analyzer was used to detect mitochondrial function. NTG induced more serious headaches in the fasting group. Both the head-scratching times and climbing-cage times in the fasting group were higher than those in normal-diet group. More ROS and inflammatory factors, such as IL-6 and IL-1β, were induced in low-glucose conditions. Seahorse showed that the basal oxygen consumption rate (OCR) and OCR for ATP production were lower in mice who had received NTG with low glucose levels than in other groups. The activity of AMPK was inhibited in this group, which may explain the Seahorse results. We concluded that in the low-glucose state, astrocytes produce more inflammatory factors, ROS, which may be a result of mitochondrial metabolism dysfunction. Improving mitochondrial function and supplying enough substrates may be an option for relieving migraine attacks.

Accelerated transcranial magnetic stimulation (aTMS) is an emerging delivery schedule of repetitive TMS (rTMS). TMS is "accelerated" by applying two or more stimulation sessions within a day. This three-part review comprehensively reports the safety/tolerability, efficacy, and stimulation parameters affecting response across disorders.

The currently available drugs to treat neuropathic pain do not provide adequate pain management. As such, other treatments including stem cells, platelet-rich plasma and plasma-derived molecules such as alpha-2 macroglobulin (A2M) are being explored because they show promising potential for neuropathic pain. The various mechanisms and immunomodulatory effects could be a desirable approach in targeting neuropathic pain. This review indicates that A2M can be highly efficacious due to its conformational change during activation and specificity of action on various cytokines. Its ability to reduce neuropathic pain can further the future of neuropathic intervention. However, there is a lack of robust clinical studies and thus further research is needed to verify and expand the understanding of its therapeutic effects.

This paper assesses the effects of percutaneous electrical nerve stimulation (PENS) on pain- and function-related outcomes by means of a scoping review of studies with single cases, case-series, quasi-experimental, and randomized or non-randomized trial designs. We consulted the PubMed, MEDLINE and EMBASE databases. Data were extracted by two reviewers. The methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro) scale for experimental studies and the Joanna Briggs Institute (JBI) tool for case reports or cases series. Mapping of the results included: (1), description of included studies; (2), summary of results; and, (3), identification of gaps in the existing literature. Eighteen articles (five randomized controlled trials, one trial protocol, nine case series and three case reports) were included. The methodological quality of the papers was moderate to high. The conditions included in the studies were heterogeneous: chronic low back pain, lower limb pain after lumbar surgery, chronic post-amputation pain, rotator cuff repair, foot surgery, knee arthroplasty, knee pain, brachial plexus injury, elbow pain and ankle instability. In addition, one study included a healthy athletic population. Interventions were also highly heterogeneous in terms of sessions, electrical current parameters, or time of treatment. Most studies observed positive effects of PENS targeting nerve tissue against the control group; however, due to the heterogeneity in the populations, interventions, and follow-up periods, pooling analyses were not possible. Based on the available literature, PENS interventions targeting peripheral nerves might be considered as a potential therapeutic strategy for improving pain-related and functional outcomes. Nevertheless, further research considering important methodological quality issues (e.g., inclusion of control groups, larger sample sizes and comparatives between electric current parameters) are needed prior to recommending its use in clinical practice.