Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function.

Background: Chronic neuropathic pain (NP) is a complex disease that results from damage or presumed damage to the somatosensory nervous system. Current treatment regimens are often ineffective. The major impediment in developing effective treatments is our limited understanding of the underlying mechanisms. Preclinical evidence suggests that glial changes are crucial for the development of NP and a recent study reported oscillatory activity differences within the ascending pain pathway at frequencies similar to that of cyclic gliotransmission in NP. Furthermore, there is evidence that glial modifying medications may be effective in treating NP. The aim of this Phase I open-label clinical trial is to determine whether glial modifying medication palmitoylethanolamide (PEA) will reduce NP and whether this is associated with reductions in oscillatory activity within the pain pathway. Methods: We investigated whether 6 weeks of PEA treatment would reduce pain and infra-slow oscillatory activity within the ascending trigeminal pathway in 22 individuals (17 females) with chronic orofacial NP. Results: PEA reduced pain in 16 (73%) of the 22 subjects, 11 subjects showed pain reduction of over 20%. Whilst both the responders and non-responders showed reductions in infra-slow oscillatory activity where orofacial nociceptor afferents terminate in the brainstem, only responders displayed reductions in the thalamus. Furthermore, functional connections between the brainstem and thalamus were altered only in responders. Conclusion: PEA is effective at relieving NP. This reduction is coupled to a reduction in resting oscillations along the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission

Green chemiluminescence from a bis-cyclometalated iridium(III) complex with an ancillary bathophenanthroline disulfonate ligand

The reaction of a fluorinated iridium complex with cerium(IV) and organic reducing agents generates an intense emission with a significant hypsochromic shift compared to contemporary chemically-initiated luminescence from metal complexes

Microstructural changes in the trigeminal nerve of patients with episodic migraine assessed using magnetic resonance imaging

Background: There is histological evidence of microstructural changes in the zygomaticotemporal branch of the trigeminal nerve in migraineurs. This raises the possibility that altered trigeminal nerve properties contribute to migraine pathophysiology. Whilst it is not possible to explore the anatomy of small trigeminal nerve branches it is possible to explore the anatomy of the trigeminal root entry zone using magnetic resonance imaging in humans. The aim of this investigation is to assess the microstructure of the trigeminal nerve in vivo to determine if nerve alterations occur in individuals with episodic migraine. Methods: In 39 migraineurs and 39 matched controls, T1-weighted anatomical images were used to calculate the volume (mm3) and maximal cross-sectional area of the trigeminal nerve root entry zone; diffusion tensor images were used to calculate fractional anisotropy, mean diffusion, axial diffusion and radial diffusion. Results: There were significant differences between the left and right nerve of controls and migraineurs with respect to volume and not cross-sectional area. Migraineurs displayed reduced axial diffusion in the right nerve compared to the left nerve, and reduced fractional anisotropy in the left nerve compared to left controls. Furthermore, although there were no differences in mean diffusion or radial diffusion, regional analysis of the nerve revealed significantly greater radial diffusion in the middle and rostral portion of the left trigeminal nerve in migraineurs compared with controls. Conclusions: Migraine pathophysiology is associated with microstructural abnormalities within the trigeminal nerve that are consistent with histological evidence of altered myelin and/or organization. These peripheral nerve changes may provide further insight into migraine pathophysiology and enable a greater understanding for targeted treatments of pain alleviation

A Multicomponent eHealth Intervention for Family Carers for People Affected by Psychosis: A Coproduced Design and Build Study

Background: Psychosis, including schizophrenia, is the most common severe mental illness affecting 1% of the population worldwide. A large number of people provide long-term support and care for a relative with psychosis. Although psychoeducational interventions, especially those delivered through a face-to-face group format, have an established evidence base for improving the caregiving experience, well-being, and health outcomes, large-scale implementation and access remain limited. There is a demand for such provision to be made through the internet for greater flexibility and wider access. Objective: This study aimed to integrate participatory research methodologies by the public, patients, and carers into the eHealth (electronic health) intervention design and build process to improve the product’s usability and acceptability. Methods: We adapted a structured eHealth intervention build method to include participatory research activities involving key stakeholders and end users to co-design and coproduce our intervention. An expert advisory group (EAG) comprising public involvement members led the formative design and build work using an agile build process. Carers independent from the study were consulted on the evolving drafts of the intervention prototype through focus group meetings. These results were fed back into the intervention build work continuously to ensure end users’ input inform every stage of the process. Results: An EAG comprising individuals with lived experience of psychosis, carers, health care professionals, researchers, voluntary organization workers, and eLearning experts (n=14) was established. A total of 4 coproduction workshops were held over 1 year during which the alpha and beta prototypes were designed and built through the participatory research work. Alongside this, 2 rounds of focus group study with carers (n=24, in 4 groups) were conducted to seek consultation on end users’ views and ideas to optimize the intervention design and usability. Finally, the EAG carried out a Web-based walk-through exercise on the intervention prototype and further refined it to make it ready for an online usability test. The final product contains multiple sections providing information on psychosis and related caregiving topics and interactive discussion forums with experts and peers for psychosocial support. It provides psychoeducation and psychosocial support for carers through the internet, promoting flexible access and individualized choices of information and support. Conclusions: The participatory research work led to the coproduction of a eHealth intervention called COPe-support (Carers fOr People with Psychosis e-support). We believe the study methodology, results, and output have optimized the intervention design and usability, fitting the end users’ needs and usage pattern. COPe-support is currently being tested for its effectiveness in promoting carers’ health outcome through an online randomized controlled trial. Trial Registration: ISRCTN Registry ISRCTN89563420; http://www.isrctn.com/ISRCTN8956342

The effects of social service contact on teenagers in England

Objective: This study investigated outcomes of social service contact during teenage years. Method: Secondary analysis was conducted of the Longitudinal Survey of Young People in England (N = 15,770), using data on reported contact with social services resulting from teenagers’ behavior. Outcomes considered were educational achievement and aspiration, mental health, and locus of control. Inverse-probability-weighted regression adjustment was used to estimate the effect of social service contact. Results: There was no significant difference between those who received social service contact and those who did not for mental health outcome or aspiration to apply to university. Those with contact had lower odds of achieving good exam results or of being confident in university acceptance if sought. Results for locus of control were mixed. Conclusions: Attention is needed to the role of social services in supporting the education of young people in difficulty. Further research is needed on the outcomes of social services contact