Accepted

The composition of intestinal microbiota is influenced by a number of factors, including medications, which may have a substantial impact on host physiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are among those widely used medications that have been shown to alter microbiota composition in both animals and humans. Although much effort has been devoted to identify microbiota signatures associated with these medications, much less is known about the underlying mechanisms. Mucosal inflammation, changes in intestinal motility, luminal pH and bile acid metabolism, or direct drug-induced inhibitory effect on bacterial growth are all potential contributors to NSAID- and opioid-induced dysbiosis, however, only a few studies have addressed directly these issues. In addition, there is a notable overlap between the microbiota signatures of these drugs and certain diseases in which they are used, such as spondyloarthritis (SpA), rheumatoid arthritis (RA) and neuropathic pain associated with type 2 diabetes (T2D). The aims of the present review are threefold. First, we aim to provide a comprehensive up-to-date summary on the bacterial alterations caused by NSAIDs and opioids. Second, we critically review the available data on the possible underlying mechanisms of dysbiosis. Third, we review the current knowledge on gut dysbiosis associated with SpA, RA and neuropathic pain in T2D, and highlight the similarities between them and those caused by NSAIDs and opioids. We posit that drug-induced dysbiosis may contribute to the persistence of these diseases, and may potentially limit the therapeutic effect of these medications by long-term use. In this context, we will review the available literature data on the effect of probiotic supplementation and fecal microbiota transplantation on the therapeutic efficacy of NSAIDs and opioids in these diseases.

Xanthogranulomatous pyelonephritis (XGP) is a rare variant of chronic pyelonephritis, occurring in the setting of obstructive uropathy and recurrent urinary tract infections (UTIs). It is difficult to diagnose as it can be asymptomatic until late-stage disease. Localized symptoms such as flank pain and dysuria may be attributed to nephrolithiasis or UTIs without prompting need for further workup. Extrarenal manifestations, most notably fistula formation, may present distal to the kidney and not be readily attributed to a renal pathology. The only known definitive therapy is nephrectomy. A delay in diagnosis can lead to fulminant complications or a more technically difficult nephrectomy. We present three cases of XGP, which serve to highlight the possibility of earlier diagnosis and resultant management options, including the potential for nephron-saving strategies. Early clinical and radiologic suspicion through awareness of risk factors may play an important role in preventing disease progression, avoiding late-stage complications, and improving treatment outcomes.

Nalbuphine was a semisynthetic opioid analgesic widely used in the treatment of both acute and chronic pain. We developed and validated a rapid, simple and sensitive method by ultra-performance liquid chromatography-tandem mass spectrometry (MS/MS) for the simultaneous quantitation of nalbuphine in human plasma, and we reported the pharmacokinetic features of patients during general anesthesia for abdominal surgery. Sample separation was achieved on a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 μm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 3 mM of ammonium acetate aqueous solution with 0.1% formic acid. Gradient elution was used in 4.5 min with a flow rate of 0.5 mL/min at 40°C. MS detection using AB Sciex QTRAP 5500 mass spectrometer was characterized by electrospray ionization for positive ions in multiple reaction monitoring mode. Quantitative ion pairs were m/z 358.4 → 340.1 for nalbuphine and m/z 340.0 → 268.3 for nalmefene, which were used as the internal standard (IS). The calibration curves showed good linearity (r2>0.99) over concentration range of 0.1-500 ng/mL. The intra-and inter-batch precisions were within 10.67%, and accuracy ranged from 94.07 to 105.34%. The IS-normalized matrix factors were 1.02-1.03 with RSD% (≤5.82%). The recoveries ranged from 101.09 to 106.30%. In conclusion, a rapid, simple, sensitive and economical analytical method was developed and validated to detect the concentration in plasma samples obtained from patients receiving nalbuphine intravenous injection and was successfully applicated to human pharmacokinetic studies of nalbuphine.

Adverse pathophysiological and behavioral outcomes related to mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain are common following blast exposure and contribute to decreased quality of life, but underlying mechanisms and prophylactic/treatment options remain limited. The dynorphin/kappa opioid receptor (KOR) system helps regulate behavioral and inflammatory responses to stress and injury; however, it has yet to be investigated as a potential mechanism in either humans or animals exposed to blast. We hypothesized that blast-induced KOR activation mediates adverse outcomes related to inflammation and affective behavioral response.

Anesthetic gases have been known to cause damage when inhaled over long periods of time. Modern safety measures have been put in place to reduce the risk to anesthesia providers, however there is continued lack of information on providers experiencing short term effects (lethargy, fatigue, headache, slowed cognitive ability, nausea, and mucosal irritation) thereby leading to long-term sequalae (sister chromatid exchanges, micronuclei, chromosomal aberrations, and comet assays).

Neuropathic pain is a debilitating form of pain arising from injury or disease of the nervous system that affects millions of people worldwide. Despite its prevalence, the underlying mechanisms of neuropathic pain are still not fully understood. Dendritic spines are small protrusions on the surface of neurons that play an important role in synaptic transmission. Recent studies have shown that dendritic spines reorganize in the superficial and deeper laminae of the spinal cord dorsal horn with the development of neuropathic pain in multiple models of disease or injury. Given the importance of dendritic spines in synaptic transmission, it is possible that studying dendritic spines could lead to new therapeutic approaches for managing intractable pain. In this review article, we highlight the emergent role of dendritic spines in neuropathic pain, as well as discuss the potential for studying dendritic spines for the development of new therapeutics.

Caffeine consumption is a risk factor for chronic daily headache, but few studies have addressed relationships between pediatric patient caffeine levels and headache severity. We examined associations between serum and urine caffeine levels and headache severity in childhood and adolescence migraine cases.

What is the central question of this study? Peritoneal injury can result in a persistent fibroproliferative process in the abdominal cavity, causing pain and loss of function of internal organs. This study aimed to demonstrate the use of sodium butyrate (NaBu) as a potential agent to attenuate peritoneal fibrosis induced by a synthetic matrix. What is the main finding and its importance? Our findings provide the first evidence that NaBu attenuates the inflammatory, angiogenesis and fibrogenesis axes involved in the formation of peritoneal fibrovascular tissue, indicating the potential of this compound to ameliorate peritoneal fibrosis.

To describe evidence of migraine-associated tinnitus and hearing loss.

Appropriate use of opioid analgesics is a key concern within the field of pain medicine. Several methods exist to discourage abuse and facilitate effective treatment regimens. Pill counting is often cited as one such method and frequently employed in varying fashions within clinical practice. However, to date, there is no published review of the evidence to support this practice. This was a comprehensive review of the available literature that was conducted with analysis of the efficacy and practical application of pill counting during treatment of chronic pain conditions.