Rejected

Axial spondyloarthritis (axSpA) is an inflammatory disease associated with significant diagnostic delays and is commonly missed in assessments of persistent back pain.

Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats.

Hydrogels as wound dressings have received great attention in recent years. It is highly important yet challenging to develop hydrogel dressings that are biocompatible and that can promote wound healing by lowering the risk of inflammatory responses. In this work, we designed and prepared zwitterionic dextran-based hydrogels using carboxybetaine dextran (CB-Dex) and sulfobetaine dextran (SB-Dex) as raw materials, respectively. The efficacy of CB-Dex and SB-Dex hydrogels in promoting wound recovery was evaluated using a mouse skin wound model. Results suggested that the zwitterionic dextran wound dressings showed a faster healing rate than natural dextran hydrogel and a commercial wound dressing (Duoderm film) due to their excellent protein resistance and capacity to scavenge free hydroxyl radicals. In addition, both CB-Dex and SB-Dex hydrogel wound dressings showed excellent cytocompatibility with NIH3T3 and L929 cells, as well as antibacterial adhesion against and . Furthermore, both zwitterionic hydrogels demonstrated self-healing properties and can be stretched to adapt to irregular full-thickness wound beds. More importantly, they can be removed from the wound site painlessly by washing with normal saline. Overall, this work provided a new pathway to fabricate multifunctional polysaccharide hydrogels for wound treatment and pain relief when changing wound dressings.

Morphine is a standard analgesic drug for postoperative pain therapy. This study aimed to evaluate the pharmacokinetics of morphine and its active metabolite morphine-6-glucuronide (M6G) in cardiac surgery  patients during postoperative analgesia.

In order to bridge the gap of information between the in silico model and human subjects, we evaluated torsadogenic risk of cisapride, dl-sotalol, bepridil and verapamil selected from 12 training compounds in the comprehensive in vitro proarrhythmia assay (CiPA) using the chronic atrioventricular block monkeys. Cisapride (0, 1 and 5 mg/kg, n=5 for each dose), dl-sotalol (0, 1, 3 and 10 mg/kg, n=5 for each dose), bepridil (0, 10 and 100 mg/kg, n=4 for each dose), verapamil (0, 1.5, 15 and 75 mg/kg, n=4 for each dose) were orally administered to the monkeys in conscious state. Five mg/kg of cisapride, 1, 3 and 10 mg/kg of dl-sotalol and 100 mg/kg of bepridil prolonged ΔΔQTcF, which was not observed by verapamil. Torsade de pointes was induced by 5 mg/kg of cisapride in 2 out of 5 animals, by 10 mg/kg of dl-sotalol in 5 out of 5 and by 100 mg/kg of bepridil in 2 out of 4, which was not induced by verapamil. These torsadogenic doses were normalized by their maximum clinical daily ones to estimate torsadogenic risk. The order of risk was dl-sotalol > bepridil ≥ cisapride > verapamil in our study. Since the order was bepridil ≥ dl-sotalol > cispride > verapamil in CiPA in silico mechanistic model validation, sympathetic regulation on the heart may play a pivotal role in the onset of torsade de pointes in vivo.

Osteoarthritis (OA) is the most common degenerative joint disorder with no effective drugs. Puerarin is a dietary supplement that has wide-ranging pharmacological effects. This study aimed to investigate the effects of Puerarin on OA. The effects of Puerarin on apoptosis, extracellular matrix (ECM) metabolism, and inflammation-related factors were assessed; also, the nuclear factor-κB (NF-κB) signaling pathway and Nrf2/HO-1 (nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1) axis were evaluated to elucidate the working mechanism of Puerarin. Mice were fed with Puerarin to evaluate the therapeutic effect of Puerarin on Osteoarthritis in vivo. The results showed that Puerarin suppressed inflammatory mediators and apoptosis induced by IL-1β treatment in chondrocytes, it may also suppress ECM degradation in IL-1β treated chondrocytes. The mechanism study revealed that Nrf2/HO-1 pathway is involved in Puerarin induced inhibition of NF-κB signaling pathway. Finally, in vivo study demonstrated that Puerarin could postpone the progression of OA in mice and relieve the symptoms of pain. In conclusion, Puerarin may potentially alleviate OA progression, and the mechanism may relate to the Nrf2/HO-1 pathway regulation.

Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH).

Headache is considered one of the most frequent neurological manifestations of COVID-19. This work aimed to identify the relative frequency of COVID-19 related headache and to clarify the impact of clinical, laboratory findings of COVID-19 infection on headache occurrence and its response to analgesics.

The long-term effects of intimate partner violence (IPV) on physical health outcomes and health-related behaviors are underresearched in comparison to the effects on mental health and pregnancy. This systematic review examines the recent research in this area from 2012 through 2019.

This is a comprehensive review of the literature regarding post-surgical cutaneous nerve entrapment, epidemiology, pathophysiology, and clinical presentation. It focuses mainly on nerve entrapment leading to chronic pain and the available therapies.