Rejected

Ultraviolet (UV) irradiation can modulate host immune responses and this approach is a novel application for treating endodontic infections and inflammation in root canals.

Chronic pain is a debilitating medical problem that is difficult to treat. Neuroinflammatory pathways have emerged as a potential therapeutic target, as preclinical studies have demonstrated that glial cells and neuroglial interactions play a role in the establishment and maintenance of pain. Recently, we used positron emission tomography (PET) to demonstrate increased levels of 18 kDa translocator protein (TSPO) binding, a marker of glial activation, in patients with chronic low back pain (cLBP). Cannabidiol (CBD) is a glial inhibitor in animal models, but studies have not assessed whether CBD reduces neuroinflammation in humans. The principal aim of this trial is to evaluate whether CBD, compared with placebo, affects neuroinflammation, as measured by TSPO levels.

The current manuscript presents a protocol for a systematic review and meta-analysis of the evidence regarding the determinants of responsiveness to multidisciplinary management of chronic pain, with pain intensity, pain-related interference, physical functioning and health-related quality of life as the main outcomes, with consideration to multiple secondary outcomes.

Surgical patients are commonly prescribed more opioids at discharge than needed to manage their postoperative pain. These excess opioids increase the risks of new persistent opioid use, opioid-induced ventilatory impairment and opioid diversion. This study tests the effectiveness of two behavioural nudges, one based on peer behaviour and one based on best practice guidelines, in reducing excessive postoperative opioid prescriptions.

 The treatment of painful neuroma remains challenging. Recently, a nerve-end capping technique using a bioabsorbable nerve conduit was newly introduced to treat amputation neuroma. A collagen-coated polyglycolic acid (PGA) conduit has been commercially available for the reconstruction of peripheral nerve defects, yielding successful clinical outcomes. However, no experimental research has been conducted using this PGA nerve conduit as capping device for treating amputation neuroma. The purpose of this study was to investigate nerve-end capping treatment with the PGA conduit in the rat sciatic nerve amputation model, focusing on histological scar formation and neuroinflammation.

To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhu & Co. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (≥18 years) and 20 children (1-5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.

Saikosaponin A (SSA) is the main active ingredient of roots of the East Asian medicinal plant, L. The present study was aimed at delving into the analgesic properties of SSA in a model of chronic inflammatory pain. To this end, rats were initially treated intraplantarly with complete Freund's adjuvant for induction of hyperalgesia. Twenty-four hours later, rats were acutely treated with SSA (0, 1 and 2 mg/kg, i.p.) and exposed to the Von Frey monofilament test or Randall-Selitto paw pressure test for assessment of mechanical hyperalgesia. Treatment with 2 mg/kg SSA had analgesic effects: the nocifensive reaction (paw withdrawal) occurred later and required application of the nociceptive stimulus at a stronger pressure. The analgesic effects of SSA were of magnitude comparable to that of the effects exerted by the reference compound, acetyl salicylic acid (100 mg/kg, i.p.). The well-described anti-inflammatory properties of SSA likely underlie its analgesic effects.

Local cooling with ice massage is a practical and inexpensive technique to decrease perceptual stress and improve motor performance in hot environments. However, it is unknown whether local cooling with ice massage reduces perceptual responses to exercise and improves performance in a normothermic environment. Thus, we investigated whether ice massage on the calf muscles before a 4 km running time trial (TT) reduced the ratings of perceived exertion (RPE) and perceived muscle pain, thereby improving exercise performance in a normothermic environment. After familiarizations, fourteen recreationally endurance-trained men (age = 21.3 ± 1.2 years; body weight = 67.5 ± 9.2 kg; height = 173.0 ± 5.0 cm) underwent two TT on a 400 m track in normothermic conditions with or without ice massage before the trial. The time of running, RPE, and pain perception were recorded every 400 m throughout the TT. The local cooling with ice massage increased the mean speed (~ 5.2%, p = 0.03) and decreased the time to complete the TT (~ 5.5%, p = 0.03). Accordingly, ice massage also reduced the exercise-derived pain perception (p = 0.028), although no effect has been found in the RPE during the TT (p = 0.32). Together, these results showed that local cooling with ice massage before the exercise reduced the exercise-derived pain perception, enabling runners to increase the speed for a comparable RPE during exercise, thereby improving the TT performance in a normothermic environment.

An effective therapeutic approach based on the anti-inflammatory action of hydrogen sulfide (HS) and inhibition of carbonic anhydrases (CAs) IX and XII is proposed here for the management of arthritis. HS is a human gasotransmitter that modulates inflammatory response at low concentrations. Inhibition of CAs IX and XII can repristinate normal pH in the acidic inflamed synovial fluid, alleviating arthritis symptoms. We report here the design of HS donor─CA inhibitor (CAI) hybrid derivatives. The latter were tested in vitro as inhibitors of human CAs I, II, IV, IX, and XII, showing a markedly increased inhibition potency/isoform selectivity compared to the CAI synthetic precursors. The best compounds demonstrated the ability to consistently release HS and produce a potent pain-relieving effect in a rat model of arthritis. Compound completely reverted the pain state 45 min after administration with enhanced antihyperalgesic effect in vivo compared to the single HS donor, CAI fragment, or their co-administration.

Surgery can sometimes be the best solution for chronic musculoskeletal pain, but presurgical preparation and postsurgical rehabilitation are often required to achieve the maximum benefits. A digital musculoskeletal surgical care program was developed to support the population of patients undergoing total knee arthroplasty.