Rejected

A large bowel obstruction (LBO) is an emergency condition that requires early diagnosis and prompt treatment, and it is also crucial to identify the cause of the obstruction. Here, we describe a 76-year-old woman who presented to the hospital with a 1-day history of abdominal pain and vomiting and was diagnosed with LBO. Endoscopic findings showed that the cause of the LBO was initially determined to be a Bormann Type I tumour in the sigmoid colon. However, the surgery was performed later; the pathological findings led to the diagnosis of colonic obstruction caused by a colonic polyp in the sigmoid colon narrowed by chronic diverticulitis. Colonic polyps rarely cause LBO. Poor observation due to colonic stenosis can mask the morphology of the lesion. In cases of LBO, colonic polyps should be differentially diagnosed in addition to colon cancer.

Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is an acquired intractable disease characterized by profound fatigue, post-exertional malaise, sleep disturbance, cognitive impairment, and orthostatic intolerance, among other features. The onset often follows an infectious episode. Importantly, the various types of autonomic dysfunctions, pain, and intolerance to various stimuli in ME/CFS patients are intrinsically different from the "fatigue" of healthy individuals. In this short essay, I summarize the current diagnostic and therapeutic strategies for ME/CFS, as well as the progress in the immunological and imaging research on this intractable disease.

To investigate peripheral enthesitis with power Doppler ultrasound (PDUS) in patients presenting low back pain (LBP) and metabolic syndrome (MetS) in comparison with patients with only LBP, to correlate US scores with clinical-anthropometric characteristics, and to define any relationship between enthesitis and concurrent diffuse idiopathic hyperostosis syndrome (DISH).

Myofascial syndrome is a common cause of chronic musculoskeletal pain. It is associated with movement restriction and is characterized by myofascial pain syndrome (MPS). Myofascial trigger points (MTPs) represent tender areas of the muscle where painful symptoms are elicited whenever stimulated. Although pathophysiology of MTPs is unclear, some authors report that they coincide with motor plates at the innervation zone (IZ). Trigger points of the tibialis anterior muscle are located at the anterior third of the muscle.

Neuropathic pain (NP) is a severe, chronic inflammatory condition affecting both the central and peripheral nervous systems and is resistant to standard treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat NP, but they are not the best option due to their limited penetration of the blood-brain barrier and the gastrointestinal side effects associated with long-term use. We recently reported a new series of benzamide derivatives that inhibit cyclooxygenase 2 (COX2) with comparable selectivity to celecoxib and tolerable side effects. Among these derivatives, 4-chloro-N-(2-(4-chlorophenyl)-1-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzamide (4b) demonstrated potent anti-inflammatory and analgesic properties, as well as 32-fold greater CNS accessibility than celecoxib. We aim to investigate the anti-inflammatory and anti-nociceptive effects of 4b against NP utilizing chronic constriction injury (CCI) model of neuropathy, elucidating the molecular mechanisms involved in its effect on both the peripheral (sciatic nerve) and central (brainstem) levels.

Opioids have been used for analgesia and anesthesia mainly via activation of central opioid mu-receptors (MORs). It also causes overdose deaths due to ventilatory failure, in which FNT is the deadest. Rapid intravenous (IV) injection of overdose FNT triggers a sudden death within a few minutes or even seconds, but the relevant mechanism remains unclear. Because bolus IV injection of FNT at a low dose produced a vagal-mediated brief apnea (Zhuang et al, AJP 2012), This study was aimed to characterize the cardiorespiratory disorders responsible for the sudden death and determine the vagal role in generating the lethal ventilatory arrest. EMGs of external and internal intercostal (EMG and EMG ), thyroarytenoid and superior pharyngeal constrictor muscles (EMG and EMG ) were simultaneously recorded before and after IV injection of FNT in the anesthetized vagal intact and vagotomized rats. The optical fiber scope of an oral video camera was applied to visualize the vocal and pharyngeal responses. Immunohistochemical approach was used to define the presence of MOR expression in the pulmonary vagal sensory neurons retrogradely labeled by DiI. FNT induced an apnea or a lethal ventilatory arrest in a dose-dependent manner associated with hypotension and bradycardia. The apnea/ventilatory arrest was characterized by silence of EMG with tonic discharges of EMG , EMG , and EMG , i.e., the central apnea (expiratory) coupled with vocal closure and pharyngeal constriction/collapse and chest wall rigidity (triple-apnea). Vagotomy abolished the evoked cardiorespiratory responses. MOR expression in vagal pulmonary neurons, especially C-neurons of the nodose and jugular ganglia. Our results suggest that rapid IV injection of FNT at a high dose uniquely causes a vagal-mediated triple-apnea, leading to the sudden death in anesthetized rats.

NMDA receptor (NMDAr) plays an important role in synaptic plasticity and one of the targets for chronic pain management is antagonism of the NMDA receptors (NMDAr). Agmatine is an endogenous aminoguanidine that preferentially antagonizes GluN2B-containing NMDArs. Our previous studies showed that the intrathecal administration of agmatine, an endogenous aminoguanidine that selectively antagonizes GluN2B-containing NMDArs, reverses the mechanical hypersensitivity without motor side effects. In this study, we demonstrated the spinal modulatory effect of agmatine and other NMDAr antagonists utilizing calcium imaging. The aim of this study is to use a newly developed NMDAr-mediated calcium transient assay (Figure 1.) in ex vivo mouse spinal cord slices and examine the effect of agmatine and other NMDAr antagonists in this assay. We hypothesize that agmatine and other NMDAr antagonists can dose-dependently inhibit NMDAr-mediated calcium transient in mouse spinal cord dorsal horn. Female and male ICR mice (4-6 weeks) were perfused before spinal cord extraction and ex vivo spinal slices were incubated with the calcium indicator dye Fluo-4. Intracellular Ca was visualized by single plane two-photon microscopy. Time-lapse of images were acquired and the peak amplitude of fluorescence intensity was analyzed by Student's t-test. We found that NMDAr-mediated calcium transients were elicited by an NMDA drug mixture containing NMDAr agonists (NMDA, glycine) and AMPA receptor antagonists (NBQX). 5mM agmatine incubation significantly attenuated the NMDAr-mediated calcium transients compared to the control. Increasing agmatine concentration dose-dependently attenuates NMDAr-mediated calcium transients. Other NMDAr antagonists including AP5 and ifenprodil, showed dose-dependent inhibition of NMDAr-mediated calcium transients, supporting that the newly developed calcium imaging assay is NMDAr specific. These data suggest that agmatine attenuates NMDAr-mediated calcium transients in the spinal cord dorsal horn, which is consistent with our previous research demonstrating that agmatine is an effective inhibitor of NMDAr in the spinal cord.

Although pain and sepsis are standard comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ damage caused by sepsis remain contradictory and inconclusive. Here, we tested the hypothesis that morphine, the gold standard narcotic analgesic, modifies behavioral and hippocampal structural defects induced by sepsis in rats. Sepsis was induced with cecal ligation and puncture (CLP) and behavioral studies were undertaken 24 hr later in septic and/or morphine-treated animals. The induction of sepsis or exposure to morphine (7 mg/kg) elicited similar: (i) falls in systolic blood pressure, (ii) alterations in spatial memory and learning tested by the Morris water maze (increases in escape latency, and decreases in time spent on quadrant plate, distance travelled, and number of crossings), and (iii) depression of exploratory behavior measured by the new object recognition test. These hemodynamic and cognitive defects were significantly exaggerated in septic rats treated with morphine compared with individual interventions. Similar patterns of amplified inflammatory (IL-1β) and histopathological signs of hippocampal damage (neuronal degeneration, satellitosis, and neuronophagia) were noted in morphine-treated septic rats. We also show that the presence of intact opioid receptors is mandatory for the elicitation of behavioral and hemodynamic effects of morphine because no such effects were observed after simultaneous blockade of these receptors by naloxone. Together, these findings suggest that morphine acts probably via opioid receptors to provoke sepsis manifestations of inflammation, and behavioral and hippocampal deficits.

Central poststroke pain (CPSP) is a central neuropathic pain syndrome that occurs following a stroke and mainly manifests as pain and paresthesia in the body region corresponding to the brain injury area. At present, due to the lack of clinical attention given to CPSP, patients suffer from long-term pain that seriously affects their quality of life. Current literature indicates that microRNA (miR)-223 can impede inflammation and prevent collateral damage. The NLR family pyrin domain containing 3 (NLRP3) inflammasome induces IL-18 and IL-1β secretion and maturation and participates in the inflammatory response. Previous evidence has confirmed that miR-223 can negatively regulate NLRP3 in the development of inflammatory responses. However, whether the miR-223 targeting of NLRP3 is involved in CPSP remains unclear. In the present study, the expression of miR-223 was detected by reverse transcription-quantitative PCR analysis. The expression levels of NLRP3, caspase-1, ASC, IL-18, IL-1β, ERK1/2, p-ERK1/2 and GFAP were detected by western blot analysis. The results demonstrated that thalamic hemorrhagic stroke triggered by microinjection of collagenase Ⅳ (Coll IV) into the ventral posterior lateral (VPL) nucleus results in pain hypersensitivity. miR-223 expression level were significantly reduced in the CPSP model. The expression levels of NLRP3, caspase-1, ASC, IL-18 and IL-1β were significantly increased in the CPSP model. The expression level of GFAP was detected to determine astrocyte activation. The results demonstrated that astrocyte activation induced by Coll IV produced a CPSP model. The p-ERK1/2 expression level was demonstrated to be significantly increased in the CPSP model. The introduction of an miR-223 agomir significantly attenuated thalamic pain and significantly decreased the levels of NLRP3, caspase-1, ASC and proinflammatory cytokines (IL-18 and IL-1β). Furthermore, introducing a miR-223 antagomir into the VPL nucleus of naïve mice mimicked thalamic pain and significantly increased the levels of NLRP3, caspase-1, ASC and proinflammatory cytokine levels (IL-18 and IL-1β). These results indicated that miR-223 inhibited NLRP3 inflammasome activity (caspase-1, NLRP3 and ASC), which ameliorated thalamus hemorrhage-induced CPSP in mice via NLRP3 downregulation. In conclusion, these results may determine the mechanisms underlying CPSP and facilitate development of targeted therapy for CPSP.

Opioid prescriptions after surgery are major contributors to the opioid abuse epidemic. Several measures designed to limit opioid prescriptions at discharge have been evaluated. We conducted a comprehensive review and meta-analysis of the effectiveness of various types of interventions in reducing opioid prescriptions after urological surgery.