Rejected

An experimental study.

Longitudinal, population-based survey.

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1-2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

Fibromyalgia (FM) is a stress-related chronic pain disorder with common cognitive complaints. This study characterized cognitive dysfunction in patients with FM and explored whether these changes are linked to altered cortisol levels. Consecutive 44 patients with FM and 48 healthy controls were enrolled for the assessments of subjective and objective cognitive functions and diurnal levels of salivary cortisol (sampled at awakening, 30 min after awakening, 3 pm, and bedtime). All measurements were compared between the groups and evaluated for clinical correlation. The FM group had more subjective cognitive complaints and performed poorer in objective cognitive testing in memory (delayed recall in Chinese Version Verbal Learning Test and Taylor Complex Figure Test), language (Boston Naming Test), and executive domains (Wisconsin Card Sorting Test) after adjustments for education. The diurnal cortisol levels of patients with FM tended to be lower, especially at 30 min after awakening and bedtime. Moreover, moderate positive correlations existed between the Chinese Version Verbal Learning Test, Boston Naming Test and the morning cortisol levels within the FM group. We suggested the altered cognitive function in FM may be linked to stress maladaptation. Future studies are warranted to elucidate whether stress management improves cognitive performance in patients with FM.

The dramatic increases of opioid use and misuse in the past 15 years have resulted in a focus on the responsible and judicious use of opioids. In this Ethics Rounds, the commentators analyze the case of a 16-year-old girl with lymphoma and opioid misuse whose caregiver may have diverted her opioids. She is now at the end of life and prefers to die at home. The commentators, oncologists, palliative care providers, ethicists, and a medical student agree that supporting the patient's goals and practicing good opioid stewardship are not incompatible. They identify additional information that would be required to analyze the case more fully such as the nature of the evidence for misuse and diversion and whether bias inadvertently contributed to these concerns. They agree that multimodal analgesia, including but not limited to opioids, is important. Safeguards could include a contract, directly observed therapy, and/or urine drug screens. Supervision or removal of a caregiver diverting medication or admission of the patient misusing medications would be alternatives if the initial plan was unsuccessful. Such patient-centered care requires well-developed substance misuse treatment, pain management, and home hospice that are adequately reimbursed.

With the widespread growth of ambulatory surgery centers (ASCs), the number and diversity of operations performed in the outpatient setting continue to increase. In parallel, there is an increase in the proportion of patients with a history of chronic opioid use and misuse undergoing elective surgery. Patients with such opioid tolerance present a unique challenge in the ambulatory setting, given their increased requirement for postoperative opioids. Guidelines for managing perioperative pain, anticipating postoperative opioid requirements and a discharge plan to wean off of opioids, are therefore needed.

The recovery room as a central monitoring unit plays a crucial role in the perioperative care of patients. Here, the patient is monitored until the subsequent transfer to a further care ward; however, due to the previous anesthesia and surgery the recovery room also provides a high risk for (the development of) complications. The present article provides an overview of the most frequent complications to be expected in the recovery room (in adults), the diagnostics and the acute treatment.

Persistent pain despite adequate inflammation control poses a big challenge in many rheumatic diseases for patients as well as physicians. The focus of drug development over the past years was on anti-inflammatory therapies. Enormous progress has been made and several treatment options have been added. It has been observed that pain triggered by inflammation can be effectively treated by inflammation control; however, the chronic pain component remains a problem, is little studied and specific treatment options are missing. Pain is influenced by inflammatory mediators, such as cytokines, which act on peripheral nociceptors and lead to peripheral sensitization. If inflammation continues, this can potentially lead to central sensitization and chronification of pain via immigration of immune cells and/or local activation of e.g. microglia. This leads to increasing autonomization and uncoupling of pain from the actual inflammatory process. The present review deals with the question if bDMARD or tsDMARD also show benefits concerning pain processes in addition to the profound inhibitory effects on inflammation. There are preclinical data that show an influence on sensitization following the use of cytokine inhibitors. On the other hand, so far clinical data show that bDMARDs as well as tsDMARDs consistently rapidly and reliably reduce nociceptive inflammatory pain across disease entities. An effect especially on the process of central sensitization and therefore on chronification of pain cannot be finally evaluated based on the currently available data.

This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain.