Slow Transit Research Articles

Enteric tuft cells coordinate timely expulsion of the tapeworm Hymenolepis diminuta from the murine host by coordinating local but not systemic immunity.

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri.

Modified Zhizhu Pill improves the loperamide-induced slow transit constipation via gut microbiota and neurotransmitters in microbiota-gut-brain axis

BackgroundSlow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis. ObjectiveThe intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation. MethodsThe effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed. ResultsModified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota. ConclusionThese results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission.

Ameliorative effects of the mixed aqueous extract of Aurantii Fructus Immaturus and Magnoliae Officinalis Cortex on loperamide-induced STC mice

Aurantii fructus immaturus (AFI) and Magnoliae Officinalis Cortex (MOC) have been used to treat constipation in China for thousands of years. In this study, a mouse model of slow transit constipation (STC) was established by gavage of loperamide at a dose of 10 mg/kg bw/day for seven days. Seventy-two mice were randomly allocated to six groups (control, STC model, 3 g/kg AFI + MOC, 6 g/kg AFI + MOC, 12 g/kg AFI + MOC, and mosapride). A mixed aqueous extract of AFI and MOC was administered to the STC mice at the corresponding doses from the first day of modelling. Body weight, faecal water content, gastrointestinal transit time, and intestinal propulsion rate were evaluated. Serum levels of neurotransmitters and gastrointestinal hormones, colonic expression of aquaporins (AQP), and interstitial cells of Cajal (ICC) were assessed using ELISA, immunohistochemistry, and Western blot analysis. The abundance and diversity of the gut microbiota were analysed by 16S rRNA gene sequencing. The mixed aqueous extract significantly increased faecal water content and intestinal propulsion rate and shortened gastrointestinal transit time in STC mice. Furthermore, the administration of AFI and MOC significantly decreased serum vasoactive intestinal peptide (VIP), nitric oxide (NO), and somatostatin (SS) levels and increased serum motilin (MTL) levels in STC mice. The protein expression levels of AQP3 and AQP4 in the colon tissue of STC mice significantly decreased following AFI + MOC treatment, whereas those of AQP9 significantly increased. Moreover, the AFI + MOC treatment led to an increase in the number and functionality of ICCs. In addition, the relative abundances of Ruminococcus and Oscillospira increased in response to the administration of AFI + MOC in STC mice. In conclusion, the mixed aqueous extract of AFI and MOC promoted defaecation and increased intestinal mobility in STC mice. Its mechanisms of action involve modulatory effects on neurotransmitters, gastrointestinal hormones, AQPs, and ICCs. AFI + MOC treatment also improved the diversity and abundance of the gut microbiota in STC mice, particularly short-chain fatty acid-producing bacteria, which may play an important role in its beneficial effect on constipation.

Laser spectroscopy of highly charged ions at the storage ring CSRe: Schottky-based spectroscopic investigation and XUV fluorescence detector development

Laser spectroscopy stands out as a powerful tool to investigate atomic and nuclear properties and also test fundamental theories by precisely measuring the energy levels in highly charged ions. In this work, the fine-structure splitting 1s22s2S1/2−1s22p2P1/2 transition in lithium-like 16O5+ has been investigated in a laser spectroscopy experiment at the heavy-ion storage ring CSRe. The excitation resonance of the tunable narrowband UV laser and the ions was observed using a Schottky resonator with very high sensitivity. The experimental uncertainties including the ion beam velocity determination, the space charge effects, laser wavelength calibration, and angular misalignment between the laser and ion beam were analyzed, and the 2S1/2−2P1/2 transition wavelength was determined to be λ0= 103.45(38) nm. The primary source of experimental uncertainty arises from the inaccurate measurement of the high voltage applied on the electron cooler and therewith the ion beam velocity at the CSRe. In order to solve this problem, a high-precision divider to precisely measure the high-voltage of the electron cooler is under construction, which is expected to improve the present experimental accuracy by three orders of magnitude. In addition, an XUV optical detector equipped with an off-axis parabolic mirror has been developed and installed at the CSRe for the investigation of slow dipole-forbidden transitions in highly charged ions, such as hyperfine splitting and M1 transitions. The experimental studies presented here pave the way for future laser spectroscopy experiments at the CSRe as well as at the future larger-scale scientific facility HIAF in China.

Primordial black holes from slow phase transitions: a model-building perspective

We investigate the formation of primordial black holes (PBHs) through delayed vacuum decay during slow cosmic first-order phase transitions. Two specific models, the polynomial potential and the real singlet extension of the Standard Model, are used as illustrative examples. Our findings reveal that models with zero-temperature scalar potential barriers are conducive to the realization of this mechanism, as the phase transition duration is extended by the U-shaped Euclidean action. We find that the resulting PBH density is highly sensitive to the barrier height, with abundant PBH formation observed for sufficiently high barriers. Notably, the phase transition needs not to be ultra-supercooled (i.e. the parameter α ≫ 1), and the commonly used exponential nucleation approximation Γ(t) ~ eβt fails to capture the PBH formation dynamics in such models.

Effects and mechanisms of sciadonic acid on colonic transit function through regulating 5-HT4/cAMP/PKA/AQP4 signaling pathway in STC model mice

Torreya grandis (T. grandis) oil has been reported to alleviate symptoms of slow transit constipation (STC). However, the impact of sciadonic acid (SA), a distinctive fatty acid found in T. grandis oil, on the pathological progression of STC remains unclear. This study aimed to evaluate the effect of SA on STC and uncover the underlying mechanisms. The STC model was established by feeding Balb/c mice with loperamide. After 2 weeks of intervention, SA significantly improved weight loss and intestinal motility decline induced by STC, along with enhancing plasma indices and reducing colon pathological damage. SA effectively reversed the STC-induced decrease in the 5-HT4/cAMP/PKA/AQP4 signaling pathway genes and expression. Furthermore, 16S rRNA analysis demonstrated that SA mitigated the imbalance of the intestinal microbiota induced by STC, by reducing the ratio of Firmicutes to Bacteroidetes (F/B) and increasing the abundance of beneficial bacteria such as Akkermansia. In conclusion, SA intervention alleviated colonic dysfunction in STC mice. The activation of the SA-mediated 5-HT4/cAMP/PKA/AQP4 signaling pathway may serve as a potential target for STC treatment. These findings suggest that SA holds promise as a treatment option for STC and could potentially be extended to other related gut diseases for further investigation.

Gravitational wave signals from early matter domination: interpolating between fast and slow transitions

An epoch of matter domination in the early universe can enhance the primordial stochastic gravitational wave signal, potentially making it detectable to upcoming gravitational wave experiments. However, the resulting gravitational wave signal is quite sensitive to the end of the early matter-dominated epoch. If matter domination ends gradually, a cancellation results in an extremely suppressed signal, while in the limit of an instantaneous transition, there is a resonant-like enhancement. The end of the matter dominated epoch cannot be instantaneous, however, and previous analyses have used a Gaussian smoothing technique to account for this, and consider only a limited regime around the fast transition limit. In this work, we present a study of the enhanced gravitational wave signal from early matter domination without making either approximation and show how the signal smoothly evolves from the strongly suppressed to strongly enhanced regimes.

Evaluation of Polyethylene Glycol Dosing for Functional Constipation in Children.

Objective: The goal of this study was to evaluate the current use of polyethylene glycol (PEG) in a pediatric gastroenterology outpatient clinic. The primary endpoint was to determine the current weight-based PEG dosing schedules used for home cleanouts and maintenance treatment for functional constipation. The secondary endpoint was to assess the dosing efficacy for home cleanouts. Methods: This study was a retrospective cohort analysis of electronic medical records documenting new patient visits at our pediatric gastroenterology clinic between September 2017 and October 2018. Patients included in the study were 13 months to 18 years of age and prescribed PEG for an at-home cleanout and/or maintenance therapy for functional or slow transit constipation. Study participants given a clean-out regimen were divided into those who received treatment for less than 2 days or more. Cleanouts were considered successful if documented as such by the prescriber in the follow-up note or if there was documentation of clear flow. Results: Of the 201 new patients included, 112 (55.7%) received a recommendation for a home cleanout. Of these, 111 patients (99%) underwent PEG-based therapy with or without additional agents. The median weight-based PEG dose was 5.3 ± 2.4 and 4.6 ± 1.9 g/kg/day for 1- and 2-day cleanouts, respectively (P = 0.124). Of the 38 patients with documented outcomes, 28 (73.7%) were successful. We observed no statistically significant differences in the number of successful versus unsuccessful outcomes based on PEG dosing (P = 0.3) or cumulative dose exposures (P = 0.388). Similarly, we observed no significant differences when comparing those on 1-day versus 2-or-more-day cleanouts, (P = 0.17). The median weight-based maintenance PEG dose was 0.74 g/kg/day (interquartile range [IQR], 0.55, 0.96). Conclusions: While the PEG doses used by this clinic for 1-day bowel cleanouts align with the NASPGHAN best practices for colonoscopy report, patients who underwent a 2-day cleanout were provided more than double the weight-based doses. The doses were nearly 3-fold higher than the recommended doses for functional constipation home cleanouts. More information will be needed to determine if these higher doses for home cleanouts are needed for the successful management of patients with functional constipation.

Research Progress on the Mechanism of Jichuan Decoction in Treating Slow Transit Constipation

Research Progress on the Mechanism of Jichuan Decoction in Treating Slow Transit Constipation

Study on regulating AQP1, AQP3, AQP4, 5-HT, NOS1 in slow transit constipation rats by Liqi Tongbian mixture.

Liqi Tongbian is a traditional Chinese medicine (TCM) preparation that contains herbs that may treat slow transit constipation (STC). Atractylodes macrocephala, Astragalus membranaceus, Fructus aurantii, radish seed, uncooked Polygonum multiflorum, and Agastache rugosa were included in the formula for their unique qualities. The control of water transfer in the colon is greatly influenced by aquaporin 3 (AQP3). Based on this, the Liqi Tongbian mixture was used to detect the concentrations of aquaporins (AQPs), 5-HT and nitrix oxide synthase 1 (NOS1) in STC rats, and explore its effect, in order to provide a theoretical basis for the remedy of STC with TCM. Zhejiang University of Traditional Chinese Medicine provided 32 three-week-old Sprague Dawley rats of SPF-grade. The pairs licensed under SYXK (Zhejiang) 2021-0012 were kept at 20-25°C and humidity of 50-65%. The compound diphenoxylate caused constipation in the control, model, Liqi laxative (LQTB), and mosapride groups. The Liqi laxative rats were administered a mixture of traditional Chinese herbs after modeling, while mosapride was given to the other group. The levels of 5-HT, NOS1 and AQPs were tested in the feces and intestinal tissues. Comparing the condition of rat feces, it was found that the model group had significantly lower overall bulk, score and particles within 24 h compared to the control group. In comparison to mosapride, LQTB performed better. The model group had higher levels of 5-HT and NOS1 in intestinal tissue, while the LQTB and mosapride groups had decreased levels of these AQPs. LQTB had lower levels of AQP1, AQP3 and AQP4 than mosapride, while the model group had higher levels of these AQPs. Liqi Tongbian mixture works better than mosapride in improving constipation symptoms in rats with STC, and its mechanism is related to regulating the level of intestinal AQPs and neurotransmitters.

Non-Targeted RNA Sequencing: Towards the Development of Universal Clinical Diagnosis Methods for Human and Veterinary Infectious Diseases.

Metagenomics offers the potential to replace and simplify classical methods used in the clinical diagnosis of human and veterinary infectious diseases. Metagenomics boasts a high pathogen discovery rate and high specificity, advantages absent in most classical approaches. However, its widespread adoption in clinical settings is still pending, with a slow transition from research to routine use. While longer turnaround times and higher costs were once concerns, these issues are currently being addressed by automation, better chemistries, improved sequencing platforms, better databases, and automated bioinformatics analysis. However, many technical options and steps, each producing highly variable outcomes, have reduced the technology's operational value, discouraging its implementation in diagnostic labs. We present a case for utilizing non-targeted RNA sequencing (NT-RNA-seq) as an ideal metagenomics method for the detection of infectious disease-causing agents in humans and animals. Additionally, to create operational value, we propose to identify best practices for the "core" of steps that are invariably shared among many human and veterinary protocols. Reference materials, sequencing procedures, and bioinformatics standards should accelerate the validation processes necessary for the widespread adoption of this technology. Best practices could be determined through "implementation research" by a consortium of interested institutions working on common samples.

Diagnosis of Chronic Constipation.

Patients with chronic constipation (CC) usually complain of mild to severe symptoms, including hard or lumpy stools, straining, a sense of incomplete evacuation after a bowel movement, a feeling of anorectal blockage, the need for digital maneuver to assist defecation, or reduced stool frequency. In clinical practice, healthcare providers need to check for 'alarm features' indicative of a colonic malignancy, such as bloody stools, anemia, unexplained weight loss, or new-onset symptoms after 50 years of age. In the Seoul Consensus on the diagnosis and treatment of chronic constipation, the Bristol stool form scale, colonoscopy, and digital rectal examination are useful for objectively evaluating the symptoms and making a differential diagnosis of the secondary cause of constipation. If patients with CC improve to lifestyle modification or first-line therapies, the effort to determine the subtypes of CC is usually not considered. On the other hand, if conventional therapeutic strategies fail, diagnostic testing needs to be considered to distinguish between the different subtypes of functional constipation (normal-transit constipation, slow transit constipation, or defecatory disorder) because these subtypes of constipation have different therapeutic implications and a correct diagnosis is critical. In the Seoul consensus, physiological testing is recommended for patients with functional constipation who have failed to respond to treatment with available laxatives (for a minimum of 12 weeks and recommended a therapeutic regimen) or who are strongly suspected of having a defecatory disorder. The Seoul consensus contains statements of physiological testing, including balloon expulsion test, anorectal manometry, defecography, and colon transit time.

Urban mobility in the future: text analysis of mobility plans

Sustainable Urban Mobility Plans (SUMPs) or similar documents from 17 European capitals (published between 2010 and 2021) and the European SUMP guidelines have been analysed to understand how cities shape mobility and their transport systems. Text analysis is applied to identify development tendencies in a time- and cost-effective manner, without relying on traditional deep semantic analysis techniques. In addition to traditional statistical indicators, we introduce Category Term Frequency (CTF) as a new measure in text analysis. CTF reveals the number and proportion of words belonging to the same content group, namely specific mobility-related categories. The results indicate that categories describing general aspects such as the future, general transport, environment, and society are more prominently represented compared to more forward-looking categories like automation, electromobility, and sharing. The aggregated CTF of categories describing these emerging aspects is highest in the mobility plans of Copenhagen, Helsinki, Luxembourg, and Vienna, which are considered forerunners in their implementation. In general, the analysis concludes that despite recent technological developments and new business models, the examined mobility plans barely mention terms that would imply radical changes by the 2030s. Strategic documents and, thus, urban mobility developments suggest only a slow transition towards the expected levels of sustainable and smart urban mobility. These findings may contribute to understanding and (re)considering urban and transport development strategies in Europe. Furthermore, this text analysis framework provides planners and other experts with a novel tool to identify the focal areas of mobility-related (or other) documents.

Visual Analysis of Research on Chinese Phonetics Teaching Based on China National Knowledge Infrastructure

In this paper, CiteSpace analysis was used to summarize the Chinese phonetics teaching in the past 42 years for visual analysis. Firstly, we manually searched the China National Knowledge Infrastructure (CNKI) database from 1982-2024, and got 961 valid documents after de-emphasis, which were imported into CiteSpace software for the visual knowledge mapping analysis. In terms of keyword clustering, we obtained 10 keyword clusters in 4 major categories, such as phonological ontology knowledge, bias analysis, pedagogical suggestions, and country-specific analysis. In terms of keyword emergence, we found that the academic community has focused on the study of Chinese phonological ontology from 1994 to 2013, and that the term "pedagogical strategies" first appeared in 1999, followed by a slow transition in 2011, and then a slow transition in 2011, and a slow transition in 2011. Research on "teaching and learning" has always been in the hot spot. The number of articles published in 2012 and 2014 had two high points, 39 and 41, respectively. Finally, the author suggests that the research on Chinese phonetics will continue to grow, and with the rapid development of information technology, Chinese phonetics will integrate more new media and educational technology tools to improve teaching efficiency and quality.

Probability Density Reweighting of High-Temperature Molecular Dynamics.

Molecular dynamics (MD) simulation is a popular method for elucidating the structures and functions of biomolecules. However, exploring the conformational space, especially for large systems with slow transitions, often requires enhanced sampling methods. Although conducting MD at high temperatures provides a straightforward approach, resulting conformational ensembles diverge significantly from those at low temperatures. To address this discrepancy, we propose a novel probability density-based reweighting (PDR) method. PDR exhibits robust performance across four distinct systems, including a miniprotein, a cyclic peptide, a protein loop, and a protein-peptide complex. It accurately restores the conformational distributions at high temperatures to those at low temperatures. Additionally, we apply PDR to reweight previously studied high-T MD simulations of 12 protein-peptide complexes, enabling a comprehensive investigation of the conformational space of protein-peptide complexes.

Dramatically Accelerating II-I Crystal Phase Transition of Polybutene‑1 by In Situ Incorporation of H-Shape Long-Chain-Branching Structures.

This communication reports an effective strategy helping address the long-troubling melt processing issue of isotactic polybutene-1 (i-PB) caused by its extremely slow II-I crystal phase transition. The solution lies in a facile synthesis of i-PB containing H-shape long-chain-branching structures (LCB-i-PB) by applying a so-called ω-alkenylmethyldichlorosilane copolymerization-hydrolysis (ACH) chemistry to butene-1 polymerization with Ziegler-Natta or metallocene catalysts. It is evident that the H-shape LCB structures effectively enhance chain entanglements of i-PB and induce an over-the-board acceleration of the overall melt crystallization process including nucleation, form II crystallization, and form II-form I phase transition. As i-PB usually requires up to a week to reach equilibrium of the II-I phase transition, it is found that with LCB-i-PB such a transition is almost finished within as short as 24 h to even higher degrees.

Unlocking success: key elements of sustainable business models in the wooden multistory building sector

Few studies have investigated the processes and strategic interactions among the Wooden Multistory Construction (WMC) industry actors, its customers, and local policymakers. Further insights into this field are needed for a sustainability transition in the construction sector. This study aims to explain WMC’s corporate sustainability strategies for co-creation with customers and municipalities. This was based on interviews with key informants in the sector and WMC actors using three case studies in Sweden. Our interviews focused on business processes, interactions with users and municipalities, sustainability, and innovation in the WMC market. The findings reflect the notion of a slow transition in the Swedish WMC market toward using more wood as a bearing structure, which is supported by the competitive advantages and climate performance of wood. The three case studies indicated that the corporate focus is currently placed on incremental improvements in operations, price competitiveness, and successful project management. However, in contexts where wood construction is seen as a unique advantage, collaborations between the construction industry and end users have developed and served as novel platforms for WMC market development. The study concludes that WMCl growth hinges on the industry’s housing offerings prioritizing quality, affordability, and swift construction.

Experimental study of the vacuum arc motion-diffuse transition in cup-shaped transverse magnetic field contacts

The arc in transverse magnetic field (TMF) contacts transitions to diffusion mode before current zero, affecting arc morphology and motion. TMF-generated force competes with local overheating's stagnation effect, impacting contact surface ablation. Cup-shaped TMF contacts exhibit slow, fast, and unstable transitions. Arc voltage declines gently, rapidly, or in repeated steps. Peak current, contact diameter, contact piece structure, and iron core influence transition characteristics. Transition energy increases linearly with peak current. Larger contact diameter and iron cores make transition constant earlier and transition current higher. Compared to circular contacts, annular contacts delay transition constant and widen transition current range. Scanning electron microscope (SEM) images showed that the ablation cathode surfaces exhibited five morphologies: melting pit, periphery, lamellar, particle, and pore. Energy dispersive spectrum (EDS) analyses show that the periphery has a higher Cu content than the interior, suggesting less Cu loss during fracture and less droplet splashing. The peripheral Cu content is comparable between the two contacts, 62.94 % vs. 62.37 %. However, the interior Cu content of contact NO.4 is higher than NO.6 at 60.54 % vs. 56.26 %. This indicates that the difference in the effect of fast and slow transitions on the cathode surface activity is mainly in the interior region.

Radial oscillations of hybrid stars and neutron stars including delta baryons: the effect of a slow quark phase transition

We study radial oscillations of hybrid neutron stars composed of hadronic external layers followed by a quark matter core. We employ a density-dependent relativistic mean-field model including hyperons and Δ baryons to describe hadronic matter, and a density-dependent quark model for quark matter. We obtain the ten lowest eigenfrequencies and the corresponding oscillation functions of N, N+Δ, N+H, and N+H+Δ equations-of-state with a phase transition to the quark matter at 1.4 and 1.8 M ⊙, focusing on the effects of a slow phase transition at the hadron-quark interface. We observe that the maximum mass is reached before the fundamental mode's frequency vanishes for slow phase transitions, suggesting that some stellar configurations with higher central densities than the maximum mass remain stable even when they undergo small radial perturbations. Future gravitational wave detectors and multi-messenger astronomy, complemented by robust microscopic models enabling exploration of various neutron star compositions, including hyperon content, are anticipated to impose precise limitations on the equation of state of baryonic matter under high-density conditions.

Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.

The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose. The administration of morphine (3 mg/kg), hydromorphone (0.4 mg/kg), or fentanyl (0.03 mg/kg) suppressed glutamate-induced nociceptive response, but not veratrine-induced nociceptive response at the same doses. However, high doses of morphine (10 mg/kg), hydromorphone (2 mg/kg), or fentanyl (0.1 mg/kg) produced a significant reduction in the veratrine-induced nociceptive response. These results indicate that high doses are required when using morphine, hydromorphone, or fentanyl for sodium channel-related neuropathic pain, such as ectopic activity. As a result, concerns have arisen about overdose and abuse if the dose of opioids is steadily increased to relieve pain. In contrast, trimebutine (100 mg/kg) and fentanyl analog isobutyrylfentanyl (iBF; 0.1 mg/kg) suppressed both glutamate- and veratrine-induced nociceptive response. Furthermore, nor-isobutyrylfentanyl (nor-iBF; 1 mg/kg), which is a metabolite of iBF, suppressed veratrine-induced nociceptive response. Besides, the optimal antinociceptive dose of iBF, unlike fentanyl, only slightly increased locomotor activity and did not slow gastrointestinal transit. Cancer pain is a complex condition driven by inflammatory, neuropathic, and cancer-specific mechanisms. Thus, iBF may have the potential to be a superior analgesic than fentanyl.