Accepted

Abdominal surgeries are frequently associated with the development of post-surgical adhesions. These are irreversible fibrotic scar bands that appear between abdominal organs and the abdominal wall. Patients suffering from adhesions are at risk of severe complications, such as small bowel obstruction, chronic pelvic pain, or infertility. To date, no cure exists, and the understanding of underlying molecular mechanisms of adhesion formation is incomplete. The current paradigm largely relies on sterile injury mouse models. However, abdominal surgeries in human patients are rarely completely sterile procedures. Here, we describe a modular surgical procedure for simultaneous or separate induction of sterile injury and microbial contamination. Combined, these insults synergistically lead to adhesion formation in the mouse peritoneal cavity. Surgical trauma is confined to a localized sterile injury of the peritoneum. Microbial contamination of the peritoneal cavity is induced by a limited perforation of the microbe-rich large intestine or by injection of fecal content. The presented protocol extends previous injury-based adhesion models by an additional insult through microbial contamination, which may more adequately model the clinical context of abdominal surgery. Graphical abstract.

This proof-of-concept study explores the potential of developing objective pain identification based on the analysis of electroencephalography (EEG) signals. Data were collected from participants living with chronic fibromyalgia pain ( = 4) and from healthy volunteers ( = 7) submitted to experimental pain by the application of capsaicin cream (1%) on the right upper trapezius. This data collection was conducted in two parts: (1) baseline measures including pain intensity and EEG signals, with the participant at rest; (2) active measures collected under the execution of a visuo-motor task, including EEG signals and the task performance index. The main measure for the objective identification of the presence of pain was the coefficient of variation of the upper envelope (CVUE) of the EEG signal from left fronto-central (FC5) and left temporal (T7) electrodes, in alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-43 Hz) frequency bands. The task performance index was also calculated. CVUE (%) was compared between groups: those with chronic fibromyalgia pain, healthy volunteers with "No pain" and healthy volunteers with experimentally-induced pain. The identification of the presence of pain was determined by an increased CVUE in beta (CVUE) from the EEG signals captured at the left FC5 electrode. More specifically, CVUE increased up to 20% in the pain condition at rest. In addition, no correlation was found between CVUE and pain intensity or the task performance index. These results support the objective identification of the presence of pain based on the quantification of the coefficient of variation of the upper envelope of the EEG signal.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic visceral pain with complex etiology and difficult treatment. Accumulated evidence has confirmed that the sensitization of the central nervous system plays an important role in the development of visceral pain, whereas the exact mechanisms of action of the neural pathways remain largely unknown. In the present study, a distinct neural circuit was identified from the paraventricular hypothalamic (PVH) to the ventral of lateral septal (LSV) region. This circuit was responsible for regulating visceral pain. In particular, the data indicated that the PVH CaMKIIα-positive neurons inputs to the LSV CaMKIIα-positive neurons were only activated by colorectal distention rather than somatic stimulations. The PVH-LSV CaMKIIα+ projection pathway was further confirmed by experiments containing a viral tracer. Optogenetic inhibition of PVH CaMKIIα+ inputs to LSV CaMKIIα-positive neurons suppressed visceral pain, whereas selective activation of the PVH-LSV CaMKIIα+ projection evoked visceral pain. These findings suggest the critical role of the PVH-LSV CaMKIIα+ circuit in regulating visceral pain.

The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is carried out according to the presenting pathophysiological mechanism. Anti-inflammatory treatment with glucocorticoids is therefore an option. The aim of this study was to systematically review the efficacy of glucocorticoids in CRPS.

Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events.