Rejected

Complex regional pain syndrome (CRPS) is an under diagonised, chronic pain condition commonly described occurring in the extremities. Its occurrence in the trunk is rarely reported and is thought by some to be non existent.

Visceral hypersensitivity and impaired gut barrier are crucial contributors to the pathophysiology of irritable bowel syndrome (IBS), and those are mediated via corticotropin-releasing factor (CRF)-Toll like receptor 4-pro-inflammatory cytokine signaling. Phlorizin is an inhibitor of sodium-linked glucose transporters (SGLTs), and known to have anti-cytokine properties. Thus, we hypothesized that phlorizin may improve these gastrointestinal changes in IBS, and tested this hypothesis in rat IBS models, i.e., lipopolysaccharide (LPS) or CRF-induced visceral hypersensitivity and colonic hyperpermeability. The visceral pain threshold in response to colonic balloon distention was estimated by abdominal muscle contractions by electromyogram, and colonic permeability was measured by quantifying the absorbed Evans blue in colonic tissue. Subcutaneous (s.c.) injection of phlorizin inhibited visceral hypersensitivity and colonic hyperpermeability induced by LPS in a dose-dependent manner. Phlorizin also blocked CRF-induced these gastrointestinal changes. Phlorizin is known to inhibit both SGLT1 and SGLT2, but intragastric administration of phlorizin may only inhibit SGLT1 because gut mainly expresses SGLT1. We found that intragastric phlorizin did not display any effects, but ipragliflozin, an orally active and selective SGLT2 inhibitor improved the gastrointestinal changes in the LPS model. Compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, N-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor and naloxone, an opioid receptor antagonist reversed the effects of phlorizin. In conclusions, phlorizin improved visceral hypersensitivity and colonic hyperpermeability in IBS models. These effects may result from inhibition of SGLT2, and were mediated via AMPK, NO and opioid pathways. Phlorizin may be effective for the treatment of IBS.

The primary aim of this study was to evaluate how the Game Ready© cryotherapy system impacts postoperative analgesia following lumbar fusion. The secondary aim was to study the effect of cryotherapy on blood loss, transfusion rate and recovery after surgery.

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder diagnosed using the Rome criteria, which have evolved since their original description 30 years ago. Little is known about the effects on the natural history of IBS of moving to the latest iteration, Rome IV, from the previous Rome III criteria. We conducted a 12-month longitudinal follow-up study examining this.

The two important targets to treat gout disease are (1) control the hyperuricemia by the inhibition of Xanthine Oxidase (XO) and (2) treatment of acute attacks of gout by the use of anti-inflammatory drugs. It is important to distinguish between therapy to manage hyperuricemia and to reduce acute inflammation. While reducing hyperuricemia is resolved very slowly with available drugs, gout symptoms like pain and inflammation may become persistent. The objective of this study is to find a relevant treatment with a beneficial double effect. (1) As an anti-inflammatory, analgesic, and antipyretic effect and (2) as XO inhibitory effect, which is the main objective of this study. We investigated the effect of five non-steroidal anti-inflammatory drugs (NSAIDs) against human and bovine milk xanthine oxidases (HXO and BXO) using the double enzyme detection method (DED) and molecular docking with the Autodock vina program. in vitro results show that the NSAIDs give an important inhibition to HXO and BXO with an IC of 2.04±0.13 μg/ml, 2.75±0.23 μg/ml, 1.45±0.19 μg/ml, 0.31±0.13 μg/ml and 1.27±0.11 μg/ml, for HXO, and 2.96±0.27 μg/ml, 9.46±0.13 μg/ml, 6.21±1.17 μg/ml, 0.83±0.11 μg/ml, and 3.48±0.13 μg/ml, for BXO, for respectively, Naproxen, Ibuprofen, Diclofenac, Indomethacin, and Celecoxib. Testing the inhibitory activity of these drugs on both XOs shows an important inhibition, especially from Indomethacin, which could be a promising lead compound for reducing acute inflammation and at the same time controlling hyperuricemia.

The severity of the COVID-19 pandemic has resulted in limited provision of palliative care and hospital teams have had to rise to the challenge of how to deliver care safely to people with palliative needs. Telehealth interventions have been seen as a useful resource with potential to improve clinical effectiveness.

Ruxolitinib (RUX) cream demonstrated potent anti-inflammatory and antipruritic efficacy in a phase 2 study in adults with atopic dermatitis (AD).

Pneumocephalus is a rare neuraxial blockade complication, which can be associated with severe neurologic changes.

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing painor distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affecttumor development. Previous studies examining the effects of analgesics on the development and metastasis of various tumorlines show that the effect of analgesics depends on the tumor line and analgesic used. A blanket statement that analgesicsaffect the general growth of tumors is not adequate scientific justification for withholding pain relief, and pilot studies orreferences are recommended for each specific tumor cell line and treatment combination. In this study, we evaluated the effects of 2 commonly used analgesics on tumor growth in 2 models of prostate cancer (PCa) bone metastasis. We hypothesized that a one-time injection of analgesics at the time of intratibial injection of tumor cells would not significantly impact tumor growth. Either C57BL/6 or SCID mice were injected subcutaneously with an analgesic (carprofen [5 mg/kg], or buprenorphine [0.1 mg/kg]) or vehicle (0.1 mL of saline) at the time of intratibial injection with a PCa cell line (RM1 or PC3, n = 10 to 11 per group). Tumor growth (measured by determination of tumor burden and the extent of bone involvement) and welfare (measured by nociception,locomotion, and weight) were monitored for 2 to 4 wk. Neither carprofen or buprenorphine administration consistentlyaffected tumor growth or indices of animal welfare as compared with the saline control for either cell line. This study adds to the growing body of literature demonstrating that analgesia can be compatible with scientific objectives, and that a decision to withhold analgesics must be scientifically justified and evaluated on a model-specific basis.