Rejected

In most animals, pain can compromise physiological functions and delay healing so, rapid detection of pain through behavior and inflammatory reaction with biomarkers are necessary. This study aimed to evaluate pain, physiological variations and Acute Phase Proteins (APP) in donkeys undergoing orchiectomy technique by inguinal access. For this research, 15 male northeastern donkeys kept in extensive management were selected, with a mean age of 4.5±3.1 years. All animals had the same anesthetic protocol, using dissociative anesthesia and local block with lidocaine, followed by orchiectomy by inguinal access. Due to their predisposition to complications, the inguinal technique is the most indicated to minimize complications and excessive inflammation in donkeys' orchiectomy, the donkeys were evaluated regarding behavioral assessment of pain, hematological parameters, APP and the surgical wound, during 0h, 24h, 48h and 72h. As for the physiological parameters and APP, no significant differences were observed between times, due to the use of non-steroidal anti-inflammatory drugs. In the macroscopic evaluation of the surgical wound, it was observed that there were no significant differences between the times, with animals presenting mean scores of 1.8±0.414, in 48 hours 1.6±0.507, and in 72 hours 1.6±0.507. Most animals had mild to moderate edema in the scrotum and foreskin regions. As for pain assessment, the average scores were between 2-3, representing mild and moderate pain, not requiring intervention. However, further research is needed to elucidate the behavior of PFAs in the face of variables and the creation of new pain scales for animals raised in an extensive system.

Some of the most commonly used analgesic drugs in animals are of questionable efficacy or present adverse side effects amongst the various species of reptiles. Tricyclic anti-depressants have been demonstrated to have antinociceptive effects in several animal models of pain and could be a good alternative for use in reptiles.

Slower gait speed and subjective cognitive concerns are characteristics of the motoric cognitive risk (MCR) syndrome. This study aimed to examine if changes in pain maybe hallmarks of early MCR, through investigating the magnitude of the associations of chronic pain on the risk of MCR at 4 years follow up.

Following peripheral nerve injury, extracellular ATP-mediated purinergic signaling is crucial for spinal cord microglia activation and neuropathic pain. However, the mechanisms of ATP release remain poorly understood. Here, we show that volume-regulated anion channel (VRAC) is an ATP-releasing channel and is activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Mice with microglia-specific deletion of Swell1 (also known as Lrrc8a), a VRAC essential subunit, had reduced peripheral nerve injury-induced increase in extracellular ATP in spinal cord. The mutant mice also exhibited decreased spinal microgliosis, dorsal horn neuronal hyperactivity, and both evoked and spontaneous neuropathic pain-like behaviors. We further performed high-throughput screens and identified an FDA-approved drug dicumarol as a novel and potent VRAC inhibitor. Intrathecal administration of dicumarol alleviated nerve injury-induced mechanical allodynia in mice. Our findings suggest that ATP-releasing VRAC in microglia is a key spinal cord determinant of neuropathic pain and a potential therapeutic target for this debilitating disease.

To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis.

Pain is one of the major prehospital symptoms in trauma patients and requires prompt management. Recent studies have reported insufficient analgesia after prehospital treatment in up to 43% of trauma patients, leaving significant room for improvement. Good evidence exists for prehospital use of oral transmucosal fentanyl citrate (OTFC) in the military setting. We hypothesized that the use of OTFC for trauma patients in remote and challenging environment is feasible, efficient, safe, and might be an alternative to nasal and intravenous applications.

Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain.

The GTP cyclohydrolase 1 enzyme (GTPCH1) is the rate-limiting enzyme of the tetrahydrobiopterin (BH) biosynthetic pathway. Physiologically, BH plays a crucial role as an essential cofactor for the production of catecholamine neurotransmitters, including epinephrine, norepinephrine and dopamine, as well as the gaseous signaling molecule, nitric oxide. Pathological levels of the cofactor have been reported in a number of disease states, such as inflammatory conditions, neuropathic pain and cancer. Targeting the GTPCH1 enzyme has great potential in the management of a number of disease pathologies associated with dysregulated BH physiology. This study is an in silico investigation of the human GTPCH1 enzyme using virtual screening and molecular dynamic simulation to identify molecules that can be repurposed to therapeutically target the enzyme. A three-tier molecular docking protocol was employed in the virtual screening of a comprehensive library of over 7000 approved medications and nutraceuticals in order to identify hit compounds capable of binding to the GTPCH1 binding pocket with the highest affinity. Hit compounds were further verified by molecular dynamic simulation studies to provide a detailed insight regarding the stability and nature of the binding interaction. In this study, we identify a number of drugs and natural compounds with recognized anti-inflammatory, analgesic and cytotoxic effects, including the aminosalicylate olsalazine, the antiepileptic phenytoin catechol, and the phlorotannins phlorofucofuroeckol and eckol. Our results suggest that the therapeutic and clinical effects of hit compounds may be partially attributed to the inhibition of the GTPCH1 enzyme. Notably, this study offers an understanding of the off-target effects of a number of compounds and advocates the potential role of aminosalicylates in the regulation of BH production in inflammatory disease states. It highlights an in silico drug repurposing approach to identify a potential means of safely targeting the BH biosynthetic pathway using established therapeutic agents.

Gabapentin has been adopted in Enhanced Recovery After Surgery protocols as a means to reduce opioid consumption while maintaining adequate post-operative analgesia. The purpose of our study was to review and compare changes in length of stay, opioid use, and patient reported pain scores after the addition of gabapentin into five, distinct pain protocols for posterior spinal fusion in adolescent idiopathic scoliosis.

The number of hip fractures per year worldwide is estimated to reach 6 million by the year 2050. Despite the many advantages of regional blockades when managing pain from such a fracture, these are used to a lesser extent than general analgesia. One reason is that the opportunities for training and obtaining clinical experience in applying nerve blocks can be a challenge in many clinical settings. Ultrasound image guidance based on artificial intelligence may be one way to increase nerve block success rate. We propose an approach using a deep learning semantic segmentation model with U-net architecture to identify the femoral nerve in ultrasound images. The dataset consisted of 1410 ultrasound images that were collected from 48 patients. The images were manually annotated by a clinical professional and a segmentation model was trained. After training the model for 350 epochs, the results were validated with a 10-fold cross-validation. This showed a mean Intersection over Union of 74%, with an interquartile range of 0.66-0.81.