Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice.

The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioural, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage. Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioural changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signalling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behaviour were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioural, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioural changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations.

Treatment of Chronic Plantar Fasciitis with Noninvasive Interactive Neurostimulation: A Prospective Randomized Controlled Study.

The initial treatment of plantar fasciitis should be conservative, with most cases responding to standard physiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs), heel pads, and stretching. In cases of chronic refractory symptoms, more invasive treatment could be necessary. Noninvasive interactive neurostimulation (NIN) is a form of electric therapy that works by locating areas of lower skin impedance. The objective of the present prospective randomized controlled study was to evaluate whether the use of NIN for chronic plantar fasciitis could result in greater improvement in a foot functional score, lower levels of reported pain, reduced patient consumption of NSAIDs, and greater patient satisfaction compared with electric shockwave therapy in patients without a response to standard conservative treatment. The patients were randomized using random blocks to the NIN program (group 1) or electric shockwave therapy (group 2). The outcome measurements were the pain subscale of the validated Foot Function Index (PS-FFI), patient-reported subjective assessment of the level of pain using a standard visual analog scale, and daily intake of NSAID tablets (etoricoxib 60 mg). The study group was evaluated at baseline (time 0), week 4 (time 1), and week 12 (final follow-up point). Group 1 (55 patients) experienced significantly better results compared with group 2 (49 patients) in term of the PS-FFI score, visual analog scale score, and daily intake of etoricoxib 60 mg. NIN was an effective treatment of chronic resistant plantar fasciitis, with full patient satisfaction in >90% of cases. The present prospective randomized controlled study showed superior results for noninvasive neurostimulation compared with electric shockwave therapy, in terms of the functional score, pain improvement, and use of NSAIDs.

Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice.

BACKGROUND: Enhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain. Chronic pain can interfere with specific brain areas involved in glutamate-dependent neuropsychological processes, such as cognition, memory, and decision-making. The medial prefrontal cortex (mPFC) is thought to play a critical role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain. Using an animal model of spared nerve injury (SNI) of the sciatic nerve, we assess bio-molecular modifications in glutamatergic synapses in the mPFC that underlie neuropathic pain-induced plastic changes at 30 days post-surgery. Moreover, we examine the effects of palmitoylethanolamide (PEA) administration on pain-related behaviours, as well as the cortical biochemical and morphological changes that occur in SNI animals. RESULTS: At 1 month, SNI was associated with mechanical and thermal hypersensitivity, as well as depression-like behaviour, cognitive impairments, and obsessive-compulsive activities. Moreover, we observed an overall glutamate synapse modification in the mPFC, characterized by changes in synaptic density proteins and amino acid levels. Finally, with regard to the resolution of pain and depressive-like syndrome in SNI mice, PEA restored the glutamatergic synapse proteins and changes in amino acid release. CONCLUSIONS: Given the potential role of the mPFC in pain mechanisms, our findings may provide novel insights into neuropathic pain forebrain processes and indicate PEA as a new pharmacological tool to treat neuropathic pain and the related negative affective states. Graphical Abstract Palmitoylethanolamide: a new pharmacological tool to treat neuropathic pain and the related negative affective states.

[Splenic infarction after warfarin discontinuation during atrial fibrillation]. / Infarto splenico: rara complicanza tromboembolica di fi brillazione atriale.

We describe a case of patient with splenic infarction, admitted to our department for sudden abdominal pain and fever after discontinuation of anticoagulant therapy for atrial fibrillation, complicating a dilated myocardiopathy and mechanical prosthetic valve. Diagnosis of splenic infarction was made by enhanced-contrast computed tomography, while ultrasounds and radiography were negative. Anticoagulant therapy, gold-standard treatment, was followed by fast clinical improvement. Moreover, splenic infarction should be considered in all cases of acute or chronic pain in left hypochondrium and especially in patients with emboligenous cardiopathies or atrial fibrillation, the most common arrhythmia source of peripheral embolism in clinical practice.