Category: 8. Health

A week of lavender-scented nights helped brain surgery patients sleep more deeply, shorten delirium, and feel calmer, pointing to a simple, natural aid for post-surgery care.

Study: Effects of lavender essential oil inhalation aromatherapy on postoperative sleep quality in patients with intracranial tumors: a randomized controlled trial. Image credit: pilipphoto/Shutterstock.com

A randomized controlled trial investigating the therapeutic impact of lavender essential oil aromatherapy on various postoperative measures revealed improved objective sleep quality (notably on the fourth day). It reduced anxiety on the seventh postoperative day in patients with intracranial tumors. The trial findings are published in Frontiers in Pharmacology.

Background

An intracranial tumor, commonly known as a brain tumor, is an abnormal growth of cells in or around the brain. These tumors can be benign or malignant and can significantly impair brain functions and affect the physical and mental health of affected people. In severe cases, these tumors can be life-threatening.

Surgery is the primary treatment option for intracranial tumors, which are often associated with postoperative neurocognitive dysfunctions and prolonged hospital stay. Sleep disturbances are widely recognized postoperative consequences in patients with intracranial tumors. This is associated with cognitive impairment, increased pain, anxiety, and depression, and delayed postoperative recovery.

Various pharmacological and non-pharmacological interventions are available to improve postoperative sleep quality and neurocognitive functions. However, major disadvantages of pharmacological interventions are adverse side effects, including respiratory distress. Non-pharmacological interventions, including noise reduction, eye masks, and music therapy, on the other hand, exhibit significant individual variability in response. This highlights the need for identifying effective and safe strategies to improve the postoperative health consequences of patients with intracranial tumors.

In this randomized controlled trial conducted at the Sanbo Brain Hospital, China, researchers investigated the therapeutic potential of lavender essential oil inhalation aromatherapy in improving sleep quality and shortening postoperative delirium duration in patients with intracranial tumors.

Lavender essential oil is well-known for its anti-inflammatory, anxiolytic, antidepressant, and sleep-promoting properties. It has been used widely for aromatherapy in hemodialysis patients, burn patients, and those with migraines and insomnia. The current trial aimed to extend the previously recognized anxiolytic and sleep-promoting effects of this aromatherapy in patients with intracranial tumors.     

Trial design

The trial involved 42 hospitalized patients who were scheduled for intracranial tumor surgery. The participants were randomly assigned to the intervention group and the control group.

The intervention group patients received inhalation aromatherapy with 10% lavender essential oil, administered via nasal patches at night for seven consecutive days following surgery. The control group patients did not receive any intervention. No placebo or sham control was used, which the authors note as a limitation of this study.

All enrolled patients were evaluated using validated methods for postoperative sleep quality and neurocognitive disorders.

Key findings

The chemical composition of the lavender essential oil was analyzed in the trial to ensure consistency in the chemical profile. The findings revealed the presence of 60 compounds, with linalyl acetate, linalool, and lavandulol acetate being the most abundant and significant compounds. 

Postoperative sleep quality

Several sleep quality parameters were analyzed in each study group for seven days after surgery. The findings revealed significantly longer total sleep and deep sleep durations in patients receiving lavender essential oil aromatherapy on the fourth postoperative day only, compared to the control group patients.

Overall, an improved sleep quality was observed among intervention group patients across several postoperative nights; however, a statistically significant improvement was observed only on the fourth day. This observation indicates that repeated exposures to lavender essential oil for several nights are needed to exert a measurable impact on postoperative sleep quality.

The trial findings also revealed significantly shorter sleep latency (the transition from full wakefulness to sleep) and lower sleep apnea severity and frequency of awakenings among intervention group patients compared to the control group patients.

Postoperative neurocognitive disorder

The assessment of various neurocognitive disorders revealed a significantly shorter duration of postoperative delirium among intervention group patients compared to that among control group patients. Delirium is a condition of impaired thinking and awareness that can lead to confusion, memory problems, or hallucinations. However, no significant differences were found between the groups in Mini-Mental State Examination (MMSE) scores one and three months after surgery.

Postoperative mental health outcomes

The trial reported a significant improvement in anxiety on the seventh postoperative day and a non-significant improvement in depression among intervention group patients. The observed improvement in anxiety and sleep quality due to lavender essential oil aromatherapy was more evident in female patients than in male patients. The authors caution that this subgroup finding is exploratory and based on a small sample size.

Significance

The trial findings highlight the significance of postoperative lavender essential oil inhalation aromatherapy in improving sleep quality (particularly on day four), reducing the duration of delirium, and mitigating anxiety in patients with intracranial tumors.

Notably, the trial suggests that this aromatherapy’s postoperative sleep and cognitive benefits are associated with continuous, repeated exposures to lavender essential oil for several nights, indicating that the effect of lavender essential oil may be cumulative. No significant differences were seen in pain, postoperative nausea/vomiting, complications, length of stay, or hospital cost. Further mechanistic research in larger samples is needed to understand the pattern of aromatherapy efficacy better.  

The therapeutic properties of lavender essential oil are closely associated with its chemical composition. The formulation used in this trial is characterized by high levels of linalool and linalyl acetate, and low levels of eucalyptol and camphor. Both linalool and linalyl acetate have been found to improve sleep quality by entering the circulatory system through inhalation and altering the GABAergic, cholinergic, histaminergic, and monoaminergic pathways in the limbic system.

The trial reports aromatherapy-mediated reduction in postoperative delirium duration, possibly due to the neuro-modulatory effects of lavender components and their interaction in regulating sleep and cognitive function.

Overall, the trial findings suggest that 10% lavender essential oil is safe for inhalation aromatherapy in the short-term postoperative period and may have clinical implications for improving perioperative sleep, mitigating cognitive impairment, and managing stress.

The authors note that while no adverse events were reported in this study, some literature points to possible route-dependent risks and endocrine effects in other contexts, which warrant further safety studies.

Download your PDF copy now!

The past few years have seen a boom in the market for protein- and peptide-based drugs, with the global market for peptide-based drugs expected to reach approximately $80 billion by 2032.¹ The primary reason is that peptide-based drugs can be highly effective,² leading to fewer off-target interactions and excellent biocompatibility. However, some of the major issues with these potentially game-changing therapeutic agents include their short lifespan within the body (they are prone to hydrolysis and enzymatic degradation) and their poor oral bioavailability, which is often between 1 and 2 percent.  

To date, this poor oral bioavailability² has meant that peptides have been administered parenterally (ie, via intravenous injection). Not only has the technology for successful oral administration been unavailable, but the medical need outweighed the drawbacks of regular injections; notably the peptide insulin³ has saved tens of millions of lives over the last 100 years, despite its delivery requiring injection. However, recent advances in the development of peptide-based drugs have led to improvements in peptide solubility and oral bioavailability for both linear and cyclic peptides, with several drugs being approved or entering clinical trials. For example, orally bioavailable PCSK9 inhibitor, Enlicitide (MK-0616), is currently in Phase III trials for treatment of adult hypercholesterolemia. Similarly, Icotrokinra (JNJ-2113),⁴ an orally administered peptide-based treatment for psoriasis, is currently also in Phase III trials.  

Strategies for oral bioavailability of peptides 

There are several strategies for improving oral bioavailability of peptides that are largely aimed at chemically altering the amino acids in the chain, causing cyclisation which aids delivery of the peptide to the site of interest. In addition, formulation strategies have also been explored for improving the oral bioavailability of peptides.

Altering peptides at the amino-acid level 

While the strategies for optimisation of small molecules are well established, such as adjusting lipophilicity, installation of (bio)isosteres and using prodrugs, similar strategies for use in peptides are far less developed. However, significant work has taken place in this area, which is now levelling the playing field.  

Peptide sequences can be tailored through chemical modifications that impact their in vivo behaviour and physicochemical properties. In particular, the improvement of therapeutic half-life⁵ through incorporation of non-natural amino acids, D-amino acids, PEGylation, N- and C-terminal modifications, and attachment on the side chains has afforded an extended therapeutic window of activity in vivo, leading to dosing regimens that are comparable to those of small molecules. Of these, modification of peptide sequences and attachment of lipids to enhance binding to albumin⁶ or other proteins have proven effective strategies to improve peptide half-life. 

Cyclic peptides 

Cyclic peptides are receiving increased attention⁷ and offer significant potential to address the challenges of peptide-based therapeutics. As with all peptides, when administered orally they are rapidly digested and/or have low absorption in the GI tract. However, these issues can sometimes be circumvented, for example through N-alkylation,⁸ inclusion of D-amino acids or use of disulfide, ring closing metathesis (RCM) or lactam formation as cyclisation approaches.⁷ In addition, the use of cyclic peptides in combination with some of the other outlined strategies for oral bioavailability paves the way for significant advances in drug discovery and development. 

Nanoparticles 

Nanoparticles (NPs) are defined as solid particles between one and 100nm in size that have colloidal properties when dispersed in an aqueous phase. It has consistently been shown that use of NPs can enhance solubility of poorly soluble compounds,⁹ including peptides,¹⁰ eg, through adjusting interaction with mucous barriers in the small intestine,¹¹ blocking enzyme metabolism or enabling colon-specific drug delivery. Many examples of NP-based peptide drugs are currently under investigation¹² for targeted delivery across the blood–brain barrier as well as in the treatment of breast cancer.  

Permeation enhancers 

Permeation enhancers (PEs) are designed to facilitate passage of the peptide through the skin or other barriers, thereby enhancing absorption of the drug. In the case of oral peptide medications, PEs are incorporated to alter the integrity of the intestinal epithelial barrier. These formulations often include medium-chain fatty acid-based systems, bile salts, acyl carnitines and the chelating agent EDTA.¹³  However, while these approaches can provide benefit in the treatment of indications, there are limitations: fasting is often required before and after drug administration (such as with the GLP-1 receptor agonist Rybelsus,¹⁴ which contains salcaprozate sodium (SNAC) as the PE) and some have raised safety concerns due to the potential for irreversible intestinal epithelium damage.¹³  

Self-emulsifying drug delivery systems 

Self-emulsifying drug delivery systems (SEDDS) comprise mixtures of lipids, surfactants and co-solvent that, when dispersed in gastrointestinal fluid, form emulsions and microemulsions. These can overcome barriers to absorption by providing protection from metabolism and improving penetration through the intestinal mucus layer. Currently cyclosporin A (Sandimmune/Neoral®)¹⁵ is formulated with SEDDS, which has an impressive bioavailability of 20–40 percent.  

What does the future hold? 

The field of peptide-based therapeutics is both old, with the first peptide-based drug (insulin) developed over 100 years ago, and young at the same time, with new modalities and classes of compounds continuously being developed. Due to the advances in bioavailability of peptides, peptide-based therapeutics are currently at the cusp of a revolution and will undoubtedly be an important modality for addressing unmet medical need and treatment of diseases in the future.  

Peptides and Sai Life Sciences 

Sai Life Sciences is a leader in the field of peptides and peptide-based therapeutics and is well-placed to support research and drug development efforts. With expertise in peptide synthesis, analysis, biological screening, ADME-PK characterization and storage, as well as formulation development, we can develop innovative medicines faster.  

References 

1. Rossino G, Marchese E, Galli G, et al. Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era. Molecules, 28 (20), 7165-7203, 2023. https://doi.org/10.3390/molecules28207165 
2. Chen G, Kang W, Li W, et al. Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies. Theranostics, 12 (3), 1419-1439, 2022. https://doi.org/10.7150/thno.61747  
3. Levy M. Insulin Development and Commercialization, American Chemical Society. https://www.acs.org/education/whatischemistry/landmarks/insulin.html (Accessed March 2025).  
4. Icotrokinra delivered an industry-leading combination of significant skin clearance with demonstrated tolerability in a once daily pill in Phase 3 topline results. Johnson & Johnson. https://www.jnj.com/media-center/press-releases/icotrokinra-delivered-an-industry-leading-combination-of-significant-skin-clearance-with-demonstrated-tolerability-in-a-once-daily-pill-in-phase-3-topline-results (Accessed March 2025). 
5. Mathur D, Prakash S, Anand P, et al. PEPlife: A Repository of the Half-life of Peptides. Sci. Rep., 6, 36617, 2016. https://doi.org/10.1038/srep36617 
6. Menacho-Melgar R, Decker JS, Hennigan JN, Lynch MD. A review of lipidation in the development of advanced protein and peptide therapeutics. J. Contr. Release., 295 (10), 1-12. https://doi.org/10.1016/j.jconrel.2018.12.032 
7. Merz ML, Habeshian S, Li B, et al. De novo development of small cyclic peptides that are orally bioavailable. Nat. Chem. Biol., 20, 624-633, 2024. https://doi.org/10.1038/s41589-023-01496-y 
8. Räder AFB, Reichart F, Weinmüller M, Kessler H. Improving oral bioavailability of cyclic peptides by N-methylation. Bioorg. Med. Chem., 26 (10), 2766-2773, 2018. https://doi.org/10.1016/j.bmc.2017.08.031 
9. Cao S-J, Xu S, Wang H-M, et al. Nanoparticles: Oral Delivery for Protein and Peptide Drugs. AAPS PharmSciTech, 20, 190, 2019. https://doi.org/10.1208/s12249-019-1325-z 
10. US Patent US9949924B2. Methods and compositions for oral administration of protein and peptide therapeutic agents. https://patents.google.com/patent/US9949924B2/en 
11. Ruiz-Gatón L, Espuelas S, Larrañeta E, et al. Pegylated poly(anhydride) nanoparticles for oral delivery of docetaxel. Eur. J. Pharm. Sci., 118, 165-175, 2018. https://doi.org/10.1016/j.ejps.2018.03.028 
12. Sharma R, Borah SJ, Bhawna, et al. Functionalized Peptide-Based Nanoparticles for Targeted Cancer Nanotherapeutics: A State-of-the-Art Review. ACS Omega, 7 (41), 36092–36107, 2022. https://doi.org/10.1021/acsomega.2c03974 
13. McCartney F, Gleeson JP, Brayden DJ. Safety concerns over the use of intestinal permeation enhancers: A mini-review. Tissue Barriers, 4, 2, e1176822, 2016. https://doi.org/10.1080/21688370.2016.1176822 
14. Semaglutide. Drugbank. https://go.drugbank.com/drugs/DB13928 (Accessed March 2025) 
15. Cyclosprorine. Drugbank. https://go.drugbank.com/drugs/DB00091 (Accessed March 2025) 

Introduction

Pediatric anesthesia management requires balancing adequate anesthetic depth with minimal side effects. Sevoflurane remains the preferred inhalational agent in pediatric practice due to its favorable induction characteristics and low airway irritation potential. However, it may produce excitatory phenomena during the induction and emergence phases, particularly in younger children.¹ The laryngeal mask airway (LMA) has become integral to pediatric anesthesia, facilitating spontaneous ventilation during general anesthesia for minor surgical procedures.² When insufficient anesthetic depth, LMA insertion can trigger significant protective airway reflexes, including laryngospasm and coughing.³ While deepening anesthesia effectively prevents these airway responses, higher sevoflurane concentrations have been associated with adverse neurological effects in susceptible patients, including epileptiform activity and emergence agitation, though individual patient factors significantly influence risk.^4–6 Successful LMA placement therefore requires careful optimization of anesthetic depth, quantified as the minimum alveolar concentration required for LMA insertion (MAC_LMA).

Premedication offers several advantages in pediatric anesthesia, including anxiety reduction, improved induction cooperation, enhanced anesthetic potentiation, and decreased anesthetic requirements.^7,8 Studies have shown that midazolam and dexmedetomidine effectively reduce sevoflurane requirements for LMA insertion.^9,10 However, these agents present significant limitations: delayed onset, prolonged recovery times, and potential for paradoxical agitation or hemodynamic instability.

Esketamine, the S (+) enantiomer of ketamine, has emerged as a promising alternative for pediatric premedication.¹¹ This N-methyl-D-aspartate receptor (NMDA) antagonist exhibits approximately twice the analgesic potency of racemic ketamine with fewer psychological side effects, minimal secretions, rapid onset, and shorter recovery time.¹² Unlike conventional agents, esketamine preserves airway reflexes without causing cardiovascular depression. Intranasal administration is particularly suitable for pediatric patients as it avoids injection-related distress while ensuring efficient mucosal absorption.¹³

Despite these advantages, the effect of intranasal esketamine premedication on sevoflurane requirements for LMA insertion in pediatric patients has not been investigated. This randomized controlled trial, therefore, examines whether intranasal esketamine at doses of 0.5 mg/kg and 1.0 mg/kg reduces the minimum alveolar concentration of sevoflurane required for LMA insertion in children undergoing elective strabismus surgery. We hypothesize that intranasal esketamine premedication will produce dose-dependent reductions in sevoflurane requirements, enabling adequate anesthetic depth at lower sevoflurane concentrations, thereby reducing risks associated with inadequate anesthesia and excessive volatile exposure.

Methods

Study Design and Participants

This randomized, double-blind, placebo-controlled trial was conducted at Fujian Provincial Hospital, China, from November 2023 through September 2024. The Institutional Review Board approved the study protocol (approval number K2023-01-003) on January 18, 2023, with trial registration at the Chinese Clinical Trials Registry (https://www.chictr.org.cn/showproj.html?proj=208297, ChiCTR2300076364) on October 7, 2023. Written informed consent was obtained from all parents or legal guardians before enrollment. The study adhered to the Declaration of Helsinki principles, Good Clinical Practice guidelines, and CONSORT 2025 reporting standards.¹⁴

We enrolled healthy children aged 2–5 years, classified as American Society of Anesthesiologists, with physical status I or II and scheduled for elective strabismus surgery, who were eligible for participation. We excluded patients with suspected difficult airway, recent respiratory conditions (within two weeks), recent sedative or analgesic use (within 48 hours), neuropsychiatric disorders, obesity (body mass index > 30 kg/m²), known allergies to study medications, or significant life events within one month of surgery (parental divorce, bereavement, relocation, or school changes) that might affect behavioral assessments.

Randomization and Allocation Concealment

Participants were randomly assigned in equal proportions (1:1:1) to one of three treatment groups using computer-generated randomization: control (saline), esketamine 0.5 mg/kg, or esketamine 1.0 mg/kg. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes. An independent research pharmacist, isolated from the clinical team, prepared identical syringes labeled only with study codes on the day of surgery. This double-blind design was maintained throughout the trial, with parents/guardians, healthcare providers, and outcome assessors all blinded to treatment assignments.

Premedication Protocol

All premedications were administered in a designated preoperative area with parents present to reduce anxiety. Twenty minutes before anesthetic induction, participants received one of three intranasal treatments according to their randomization: 0.9% saline solution (control), esketamine 0.5 mg/kg, or esketamine 1.0 mg/kg. Each formulation was delivered at a standardized volume of 0.04 mL/kg using a 1-mL syringe. An independent nurse administered the medication by instilling equal volumes into each nostril while the child remained supine.

Anesthetic Management

Children followed standard fasting guidelines (6–8 hours for solids, 2 hours for clear liquids) before anesthesia.¹⁵ Standard monitoring was established on arrival in the operating room, including pulse oximetry, electrocardiography, capnography, and noninvasive blood pressure measurement. We used a face mask with a semi-closed circuit system for anesthesia induction, delivering 5% sevoflurane in oxygen at 6 L/min. Ventilation progressed from initial spontaneous breathing to gentle manual assistance, maintaining end-tidal carbon dioxide between 35–45 mmHg throughout the procedure. We maintained the core temperature at 36.8 ± 0.4°C using a forced-air warming system (Bair Hugger 755; 3M Healthcare, USA). Sevoflurane concentration and end-tidal carbon dioxide were continuously monitored using a CARESCAPE Monitor B650 (GE Healthcare, USA).

Sevoflurane MAC_LMA Determination

We determined the minimum alveolar concentration of sevoflurane required for LMA insertion using Dixon’s sequential up-and-down method.¹⁶ Starting concentrations followed established protocols: 2.0% for the control group based on published data for unpremedicated children.¹⁰ The esketamine groups began at lower concentrations (1.6% for 0.5 mg/kg and 1.2% for 1.0 mg/kg) reflecting the expected dose-dependent anesthetic-sparing effect of NMDA receptor antagonists. All concentrations were equilibrated for 15 minutes before LMA insertion to ensure steady-state conditions.

To ensure unbiased assessment, a single experienced pediatric anesthesiologist (with over 200 LMA insertions annually) performed all procedures while blinded to the premedication type and sevoflurane concentration. Following each insertion attempt, the sevoflurane concentration was adjusted by ± 0.2% for the next patient in that group. An unsuccessful insertion (intentional movement, coughing, or airway reaction within one minute of insertion) led to a 0.2% increase, while a successful insertion prompted a 0.2% decrease. Independent observers, also blinded to treatment allocation, documented all responses to maintain assessment objectivity.

Anesthesia and Recovery Protocol

Following LMA placement assessment, anesthesia was deepened with 2.0 mg/kg propofol, 0.2 μg/kg sufentanil, and 0.3 mg/kg rocuronium. Maintenance anesthesia consisted of 2% sevoflurane in a 50% oxygen-air mixture. Analgesia included 1 mg/kg intravenous flurbiprofen axetil and 0.4% oxybuprocaine eye drops administered perioperatively. Antiemetic prophylaxis comprised 0.15 mg/kg dexamethasone and 0.1 mg/kg ondansetron. Following surgery and LMA removal, children were transferred to the PACU, where parents provided emotional support during recovery.

Outcome Measures

The primary outcome was the MAC_LMA of sevoflurane, determined using Dixon’s up-and-down sequential allocation method.¹⁷ This method relies on identifying crossover events—instances where a patient’s response differed from the preceding patient’s response (either successful insertion followed by unsuccessful insertion or the reverse). We calculated each crossover value as the midpoint between the end-tidal sevoflurane concentrations. The final MAC_LMA for each group was derived by averaging all crossover values.

For secondary outcomes, we assessed anesthesia induction quality using a validated 4-point scale (1 = uncooperative behavior requiring physical restraint; 4 = full cooperation or sleep state with mask acceptance).¹⁸ Emergence delirium was assessed during the first 30 minutes of recovery using the Pediatric Anesthesia Emergence Delirium scale, with scores ≥10 indicating clinically significant delirium.¹⁹ Emergence time was defined as the interval from sevoflurane discontinuation to purposeful movement in response to verbal commands. Discharge readiness from the PACU was evaluated using the modified Aldrete scoring system (threshold ≥9).²⁰ Parental satisfaction was assessed 24 hours postoperatively using a 5-point Likert scale (1 = very dissatisfied; 5 = very satisfied).²¹ Finally, behavioral changes were evaluated three days after surgery via telephone interview using the Post-Hospitalization Behavior Questionnaire for Ambulatory Surgery.²²

Adverse events were systematically documented using standardized forms throughout the perioperative period. Monitored complications included bradycardia, hypotension, laryngospasm, hypoxemia, postoperative nausea and vomiting, and nightmares. All outcome assessments were performed by a single investigator blinded to treatment allocation to ensure consistency and minimize bias.

Sample Size and Statistical Analysis

Based on Dixon’s up-and-down methodology, dose-response studies typically require 24–26 participants to obtain six crossover points.²³ Following recent methodological guidance,²⁴ implemented a fixed prespecified sample size rather than a random stopping rule. We included 30 participants in each treatment group to enhance statistical reliability and account for potential withdrawals.

Statistical analyses followed a predetermined plan. Data normality was assessed using the Shapiro–Wilk test. Continuous data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. Categorical data are expressed as frequencies and percentages. We determined the sevoflurane MAC_LMA using Dixon’s method and verified it through probit regression analysis.

Between-group comparisons employed appropriate parametric or non-parametric tests based on data distribution. One-way ANOVA with Bonferroni-adjusted post-hoc tests was applied to normally distributed variables, while the Kruskal–Wallis test, followed by Dunn’s test with Bonferroni adjustment, was used for non-normally distributed data. Categorical outcomes, including emergence delirium, behavioral changes, and adverse events, were analyzed using chi-square or Fisher’s exact tests as appropriate. All analyses were performed using IBM SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA), with statistical significance set at p < 0.05 (two-tailed).

Results

Between November 2023 and September 2024, we screened 98 children for study participation, with 90 meeting the eligibility criteria for randomization. Following protocol exclusions, the final analysis included 28 patients in the control group, 28 in the esketamine 0.5 mg/kg group, and 29 in the esketamine 1.0 mg/kg group (Figure 1). Demographic and baseline characteristics were similar across all groups (Table 1).

Figure 1 Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Our primary finding showed that intranasal esketamine premedication reduced the MAC_LMA of sevoflurane in a dose-dependent manner. These concentrations were 2.16% ± 0.18% (control, Figure 2A), 1.87% ± 0.17% (esketamine 0.5 mg/kg, Figure 2B), and 1.50% ± 0.19% (esketamine 1.0 mg/kg, Figure 2C), representing reductions of 13.4% and 30.6% from the control value, respectively. Probit regression analysis validated these findings, yielding comparable values of 2.06% (95% confidence interval [CI]: 1.85–2.26%) for control, 1.77% (95% CI: 1.60–1.95%) for esketamine 0.5 mg/kg, and 1.42% (95% CI: 1.27–1.59%) for esketamine 1.0 mg/kg groups (Figure 3).

Figure 2 Individual responses to laryngeal mask airway insertion determined by Dixon’s up-and-down method. Notes: Sequential plots showing patient responses to laryngeal mask airway insertion across three treatment groups: (A) control, (B) esketamine 0.5 mg/kg, and (C) esketamine 1.0 mg/kg. Hollow circles represent successful insertions, while solid circles indicate unsuccessful insertions (characterized by movement, coughing, or bucking within one minute of placement). The horizontal dashed lines indicate the calculated minimum alveolar concentration of sevoflurane required for laryngeal mask airway insertion: 2.16% ± 0.18% (control group), 1.87% ± 0.17% (esketamine 0.5 mg/kg group), and 1.50% ± 0.19% (esketamine 1.0 mg/kg group). These values demonstrate a dose-dependent reduction in sevoflurane requirements with intranasal esketamine premedication.

Figure 3 Probability curves for successful laryngeal mask airway insertion. Notes: Probit regression analysis showing the probability of successful laryngeal mask airway insertion relative to sevoflurane concentration. Three treatment groups are represented: control (light red line), esketamine 0.5 mg/kg (medium blue line), and esketamine 1.0 mg/kg (dark blue line). The horizontal dashed line at 0.5 probability (50%) intersects with each curve at the minimum alveolar concentration value: 2.06% for control, 1.77% for esketamine 0.5 mg/kg, and 1.42% for esketamine 1.0 mg/kg. The progressive leftward shift of the curves with increasing esketamine dosage illustrates the dose-dependent reduction in sevoflurane requirements.

The clinical benefits of esketamine extended beyond anesthetic reduction. Secondary outcomes revealed clear dose-dependent effects favoring the higher dose (Table 2). The 1.0 mg/kg group showed significantly improved cooperation during anesthesia induction compared to the control (p < 0.001), while the 0.5 mg/kg group showed no difference (p = 0.756). This dose-dependent pattern persisted through recovery: only the higher dose significantly reduced emergence delirium incidence (13.8% versus 46.4%, p = 0.007) and postoperative negative behavioral changes at day 3 (20.7% versus 53.6%, p = 0.010). Parents whose children received the higher dose reported significantly greater satisfaction (p = 0.022).

Table 2 Secondary Outcomes

Importantly, these benefits came without compromising safety or prolonging recovery. Emergence times and PACU discharge readiness were similar across all treatment groups (p = 0.331 and p = 0.589, respectively). The incidence of adverse events (including bradycardia, hypotension, laryngospasm, hypoxemia, postoperative nausea and vomiting, and nightmares) showed no significant differences between groups, and no serious complications occurred throughout the study.

Discussion

Our findings demonstrate that intranasal esketamine premedication significantly reduces sevoflurane requirements during LMA insertion in pediatric patients in a dose-dependent manner. Both tested dosages (0.5 mg/kg and 1.0 mg/kg) produced clinically meaningful reductions compared to the control, with the higher dose providing approximately twice the effect. The 1.0 mg/kg dose conferred additional clinical benefits beyond anesthetic sparing, including enhanced induction cooperation, decreased emergence delirium, and reduced postoperative negative behavioral changes at day 3 postoperatively. Crucially, these advantages were achieved without extending recovery time or increasing adverse events.

These results build upon established research on NMDA in anesthesia practice. Chen et al showed that low-dose ketamine effectively reduces sevoflurane requirements for suppressing adrenergic responses during surgical procedures,²⁵ while Hamp et al²⁶ reported similar dose-dependent reductions with S-ketamine administration. Our findings advance this knowledge by demonstrating that the intranasal route achieves comparable anesthetic-sparing effects to intravenous administration while offering distinct advantages for pediatric patients, particularly avoiding injection-related distress. The observed dose-dependent relationship is consistent with known NMDA receptor antagonism pharmacological principles.

Beyond anesthetic reduction, our study revealed important behavioral benefits. Intranasal esketamine at 1.0 mg/kg significantly reduced emergence delirium (13.8% versus 46.4%) and subsequent behavioral disturbances (20.7% versus 53.6%). These improvements align with Chen et al²⁷ who demonstrated that intravenous ketamine infusion (1 mg/kg bolus followed by 1 mg/kg/h infusion) reduced emergence delirium from 46% to 22% in children. Several mechanisms may explain these findings. Esketamine’s anti-inflammatory properties could counteract surgery-induced neuroinflammation linked to postoperative behavioral changes.^28,29 Furthermore, esketamine’s neuroprotective effects may reduce physiological stress responses to surgical and anesthetic stimuli, potentially protecting the developing brain from adverse changes.^30,31

Several factors limit the interpretation of our results. The absence of pharmacokinetic measurements precluded detailed characterization of intranasal esketamine absorption profiles. Although we selected a 20-minute premedication interval based on published data indicating peak sedative effects at approximately 16 minutes,¹¹ this fixed timing may not have captured peak drug concentrations in all patients. Our single-center design involving a specific patient population undergoing eye muscle surgery may limit applicability to other pediatric surgical contexts. Testing only two doses provides incomplete information about the optimal dose across different age groups. Additionally, the varying sevoflurane concentrations required by the Dixon methodology could theoretically affect secondary outcomes, although the substantial separation between group values makes this unlikely. Finally, despite careful blinding protocols, esketamine’s recognizable clinical effects may have compromised blinding in some cases.

Nevertheless, our study maintains high methodological standards. The randomized, double-blind, placebo-controlled design ensures robust internal validity. The Dixon sequential allocation method provided precise measurements of anesthetic requirement while protecting children from inappropriate depth. Our comprehensive pharmacodynamic and clinical outcomes assessment offers practitioners complete information about intranasal esketamine’s effects. This approach demonstrates the quantitative reduction in sevoflurane requirements and the meaningful clinical improvements in children’s perioperative experience.

Conclusion

Intranasal esketamine premedication significantly reduces sevoflurane requirements for LMA insertion in pediatric patients, with the 1.0 mg/kg dose achieving optimal results: 30.6% reduction in anesthetic requirements, improved induction cooperation, and decreased emergence agitation without prolonging recovery. These findings offer clinicians an evidence-based strategy to minimize volatile anesthetic exposure while maintaining airway safety. Although our single-center study involved a specific population undergoing strabismus surgery with one experienced operator, the results demonstrate clear clinical benefits. Future multicenter trials with diverse populations and practitioners should validate these findings and optimize dosing across age groups. Nevertheless, our data establish intranasal esketamine as a valuable tool for enhancing both safety and efficacy in pediatric anesthesia practice.

Data Sharing Statement

The corresponding author (Yanling Liao, Email: [email protected]) will make the deidentified participant data supporting this study’s findings available upon reasonable request with a methodologically sound proposal. Data will become accessible six months after publication and remain available for three years thereafter. Requestors will be required to sign a data access agreement.

Acknowledgments

We sincerely thank Professor Yusheng Yao for his valuable guidance, and all participating children and their families for their cooperation. Throughout this study, we also acknowledge the dedicated support provided by the anesthesiologists, surgeons, and nursing staff at Fujian Provincial Hospital.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study was funded by the Science and Technology Program of Haicang District of Xiamen, China (No. 350205Z20232004), Natural Science Foundation of Xiamen, China (No. 3502Z202374068), the Fujian Provincial Health Technology Project (No. 2024CXA046), the Special Project of the National Natural Science Foundation Basic Research Enhancement Program (No. JCZX202404), and the Joint Funds for the Innovation of Science and Technology, Fujian Province (No. 2023Y9309).

Disclosure

The authors declare no conflicts of interest in this work.

References

1. Lerman J. Induction of anesthesia with sevoflurane in children: curiosities and controversies. Paediatr Anaesth. 2022;32(10):1100–1103. doi:10.1111/pan.14537

2. Hsu G, von Ungern-Sternberg BS, Engelhardt T. Pediatric airway management. Curr Opin Anaesthesiol. 2021;34(3):276–283. doi:10.1097/ACO.0000000000000993

3. Li L, Zhang Z, Yao Z, et al. The impact of laryngeal mask versus other airways on perioperative respiratory adverse events in children: a systematic review and meta-analysis of randomized controlled trials. Int J Surg. 2019;64:40–48. doi:10.1016/j.ijsu.2019.02.020

4. Chao JY, Legatt AD, Yozawitz EG, et al. Electroencephalographic findings and clinical behavior during induction of anesthesia with sevoflurane in human infants: a prospective observational study. Anesth Analg. 2020;130(6):e161–e164. doi:10.1213/ANE

5. Gibert S, Sabourdin N, Louvet N, et al. Epileptogenic effect of sevoflurane: determination of the minimal alveolar concentration of sevoflurane associated with major epileptoid signs in children. Anesthesiology. 2012;117(6):1253–1261. doi:10.1097/ALN.0b013e318273e272

6. Aoyama K, Furuta M, Ameye L, et al. Risk factors for pediatric emergence delirium: a systematic review. Can J Anaesth. 2025;72(3):384–396. doi:10.1007/s12630-024-02889-w

7. Dave NM. Premedication and induction of anesthesia in pediatric patients. Indian J Anaesth. 2019;63(9):713–720. doi:10.4103/ija.IJA_491_19

8. Pereira EMM, Nascimento TSD, da Costa MG, et al. Comparison of intranasal dexmedetomidine versus oral midazolam for premedication in pediatric patients: an updated meta-analysis with trial-sequential analysis. Braz J Anesthesiol. 2024;74(5):844520. doi:10.1016/j.bjane.2024.844520

9. Savla JR, Ghai B, Bansal D, et al. Effect of intranasal dexmedetomidine or oral midazolam premedication on sevoflurane EC 50 for successful laryngeal mask airway placement in children: a randomized, double-blind, placebo-controlled trial. Paediatr Anaesth. 2014;24(4):433–439. doi:10.1111/pan.12358

10. Yao Y, Qian B, Lin Y, et al. Intranasal dexmedetomidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion and emergence delirium in children: a prospective, randomized, double-blind, placebo-controlled trial. Paediatr Anaesth. 2015;25(5):492–498. doi:10.1111/pan.12574

11. Huang J, Liu D, Bai J, et al. Median effective dose of esketamine for intranasal premedication in children with congenital heart disease. BMC Anesthesiol. 2023;23(1):129. doi:10.1186/s12871-023-02077-1

12. Zhang BS, Zhang XJ, Wang CA. The efficacy and safety of esketamine in pediatric anesthesia: a systematic review and meta-analysis. Asian J Surg. 2023;46(12):5661–5663. doi:10.1016/j.asjsur.2023.08.073

13. Hebbar KC, Reddy A, Luthra A, et al. Comparison of the efficacy of intranasal atomized dexmedetomidine versus intranasal atomized ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: a randomized controlled trial. Eur J Anaesthesiol. 2024;41(4):288–295. doi:10.1097/EJA.0000000000001936

14. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomized trials. BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123

15. Joshi GP, Abdelmalak BB, Weigel WA, et al. American society of anesthesiologists practice guidelines for preoperative fasting: carbohydrate-containing clear liquids with or without protein, chewing gum, and pediatric fasting duration-A modular update of the 2017 American society of anesthesiologists practice guidelines for preoperative fasting. Anesthesiology. 2023;138(2):132–151. doi:10.1097/ALN.0000000000004381

16. Pace NL, Stylianou MP, Warltier DC. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007;107(1):144–152. doi:10.1097/01.anes.0000267514.42592.2a

17. Yang C, Kang F, Meng W, et al. Minimum alveolar concentration-awake of sevoflurane is decreased in patients with Parkinson’s disease: an up-and-down sequential allocation trial. Clin Interv Aging. 2021;16:129–137. doi:10.2147/CIA.S291656

18. Abukawa Y, Takano K, Hobo Y, et al. The use of a scented face mask in pediatric patients may facilitate mask acceptance before anesthesia induction. Front Med Lausanne. 2023;10:1190728. doi:10.3389/fmed.2023.1190728

19. Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004;100(5):1138–1145. doi:10.1097/00000542-200405000-00015

20. Deshmukh PP, Chakole V. Post-anesthesia recovery: a comprehensive review of sampe, modified Aldrete, and white scoring systems. Cureus. 2024;16(10):e70935. doi:10.7759/cureus.70935

21. Sam CJ, Arunachalam PA, Manivasagan S, et al. Parental satisfaction with pediatric day-care surgery and its determinants in a tertiary care hospital. J Indian Assoc Pediatr Surg. 2017;22(4):226–231. doi:10.4103/jiaps.JIAPS_212_16

22. Jenkins BN, Kain ZN, Kaplan SH, et al. Revisiting a measure of child postoperative recovery: development of the post hospitalization behavior questionnaire for ambulatory surgery. Paediatr Anaesth. 2015;25(7):738–745. doi:10.1111/pan.12678

23. Görges M, Zhou G, Brant R, et al. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth. 2017;27(3):240–247. doi:10.1111/pan.13088

24. Oron AP, Souter MJ, Flournoy N. Understanding research methods: up-and-down designs for dose-finding. Anesthesiology. 2022;137(2):137–150. doi:10.1097/ALN.0000000000004282

25. Chen C, Pang Q, Tu A, et al. Effect of low-dose ketamine on MAC _BAR of sevoflurane in laparoscopic cholecystectomy: a randomized controlled trial. J Clin Pharm Ther. 2021;46(1):121–127. doi:10.1111/jcpt.13263

26. Hamp T, Baron-Stefaniak J, Krammel M, et al. Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomized, placebo-controlled, double-blinded clinical trial. Br J Anaesth. 2018;121(6):1242–1248. doi:10.1016/j.bja.2018.08.023

27. Chen JY, Jia JE, Liu TJ, et al. Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children. Can J Anaesth. 2013;60(4):385–392. doi:10.1007/s12630-013-9886-x

28. Tu W, Yuan H, Zhang S, et al. Influence of anesthetic induction of propofol combined with esketamine on perioperative stress and inflammatory responses and postoperative cognition of elderly surgical patients. Am J Transl Res. 2021;13(3):1701–1709.

29. Wang T, Weng H, Zhou H, et al. Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex. J Affect Disord. 2022;307:97–107. doi:10.1016/j.jad.2022.03.072

30. Luo T, Deng Z, Ren Q, et al. Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: a randomized controlled trial. J Clin Anesth. 2024;95:111447. doi:10.1016/j.jclinane.2024.111447

31. Sah A, Singewald N. The (neuro) inflammatory system in anxiety disorders and PTSD: potential treatment targets. Pharmacol Ther. 2025;269:108825. doi:10.1016/j.pharmthera

Published on
12/08/2025 – 7:00 GMT+2

For many living with Parkinson’s disease, the daily ritual of taking multiple pills per day can be as daunting task. But a new breakthrough from researchers at the University of South Australia could ease this burden – and potentially change the way Parkinson’s is treated forever.

After more than two years of research, scientists have developed a long-lasting weekly injection, offering hope to patients who currently face the exhausting task of taking several pills multiple times a day.

According to the Parkinson’s Foundation, the disease affects more than 10 million people globally, with men 1.5 times more likely to be diagnosed than women. It is the second-most common neurodegenerative disease after Alzheimer’s.

For those living with Parkinson’s, the standard treatment involves daily doses of medications that must be taken precisely on schedule.

“Especially concerning elderly patients, they have to remember each medication timely, and take the medication,” said University of South Australia researcher Deepa Nakmode.

“Even if they miss a single dose, they can’t perform day-to-day activities normally”.

And missing doses is alarmingly common.

“Almost 50 per cent of patients don’t take medicines as recommended by doctors, especially in chronic conditions,” said Sanjay Garg, a pharmaceutical science professor at the University of South Australia.

‘It’s going to be a game-changer’

The new injection combines two key drugs (Levodopa and Carbidopa) into one injectable dose that slowly releases the medication over the course of seven days.

“One injection will be good for one week as compared to a patient taking three or four tablets every day,” Garg said.

These drugs are primarily used to manage Parkinson’s symptoms, which commonly include tremour, muscle rigidity, and slowness of movement. Patients can also experience problems with balance, which can raise the risk of falls.

Although the new injection has not yet undergone clinical trials in humans, researchers plan to start animal testing in the coming months.

For people like Peter Willis, who was diagnosed with Parkinson’s 10 years ago and currently takes medication four times per day, the breakthrough could be life-changing.

“If you don’t take the tablet on time, you discover you can’t walk,” he said. “You sort of lose your energy as if you run out of fuel. You take the tablet again and then it picks up.”

Parkinson’s Australia has hailed the development as a major breakthrough, especially given the slow pace of progress in treatment innovation in recent years.

“It will reduce falls risks, it will mean that people can actively participate in everyday life like work and sport and volunteering,” said Parkinson’s Australia CEO Olivia Nassaris.

“It’s going to be a game-changer,” she added.

Please chooseI’m not a medical professional.Allergy and ImmunologyAnatomyAnesthesiologyBiostatisticsCardiac/Thoracic/Vascular SurgeryCardiologyCritical CareDentistryDermatologyDiabetes and EndocrinologyEmergency MedicineEpidemiology and Public HealthFamily MedicineForensic MedicineGastroenterologyGeneral PracticeGeneticsGeriatricsHealth PolicyHematologyHIV/AIDSHospital-based MedicineI’m not a medical professional.Infectious DiseaseIntegrative/Complementary MedicineInternal MedicineInternal Medicine-PediatricsMedical Education and SimulationMedical PhysicsMedical StudentNephrologyNeurological SurgeryNeurologyNuclear MedicineNutritionObstetrics and GynecologyOccupational HealthOncologyOphthalmologyOptometryOral MedicineOrthopaedicsOsteopathic MedicineOtolaryngologyPain ManagementPalliative CarePathologyPediatricsPediatric SurgeryPharmacologyPhysical Medicine and RehabilitationPlastic SurgeryPodiatryPreventive MedicinePsychiatryPsychologyPulmonologyRadiation OncologyRadiologyRheumatologySubstance Use and AddictionSurgeryTherapeuticsTraumaUrologyMiscellaneous

A new report from the government has found there is “no clinical benefit” to having a blood test for Pfas after the so-called “forever chemical” was found in local water supplies in the Blue Mountains.

The NSW Health Expert Advisory Panel on per- and polyfluoroalkyl substances (Pfas), convened by the state’s chief health officer, Dr Kerry Chant, to provide advice on the evidence and guidance related to the potential health effects, published its findings in a final report on Tuesday. All recommendations have been accepted by NSW Health.

The panel included science and health experts in cancer, hormone and heart health, epidemiology, pathology, primary care, public health and risk communication.

They found, based on the substantial research related to Pfas already undertaken, “the health effects of Pfas appear to be small”.

_{Sign up: AU Breaking News email}

Pfas are a class of manufactured chemicals used to make products that resist heat, stains, grease and water – sometimes called “forever chemicals” as they are difficult to destroy and can remain in soil, groundwater and travel long distances.

The report acknowledged that studies have reported an association with some health effects, but noted the findings are inconsistent across different studies with “limited evidence of a dose-response relationship”.

The report also found that “while clinical testing for Pfas is commercially available, the current scientific evidence indicates that there is there is no clinical benefit for an individual to have a blood test for Pfas”.

The authors stated Pfas blood tests were unlikely to guide medical care “because Pfas will be detected in most people, there are many different Pfas types and blood levels do not predict any current or future health outcomes”.

They also warned that Pfas blood test results can cause unnecessary concern and subsequent interventions may cause harms.

The report recommended that “should a health care provider order a blood test for Pfas for a patient, the health care provider should provide clear contextual information about the test and its limitations to the patient, to manage expectations and avoid misinterpretation”.

The authors also suggest doctors can support patients concerned with their serum PFAS levels by engaging in usual preventative health interventions, “as many of the health conditions potentially associated with PFAS are common in the community and are associated with well-established risk factors”.

The panel acknowledged their recommendation differs from the National Academies of Science Engineering and Medicine (NASEM), an independent institution in the United States, whose guidance documents recommended individual blood testing and the use of blood levels to inform clinical care.

They also noted the Agency for Toxic Substances and Disease Registry, overseen by the US Centers for Disease Control and Prevention, gives advice to clinicians on managing and evaluating Pfas exposure and has not adopted NASEM’s recommendations on individual blood testing and health-based screening based on Pfas blood levels.

Jon Dee, the convener of the Stop Pfas community group in the Blue Mountains, said 25 people in the area had paid $500 out of pocket to have the blood test for Pfas.

Dee said they wanted to see how their blood test compared with the areas of Williamtown, Oakey and Katherine, which were contaminated with Pfas due to firefighting activities on nearby defence force bases.

“If you look at the average blood test level of people in the Blue Mountains, we are two to three times higher than the average Pfas levels in those defence communities that have been compensated by the federal government,” Dee said.

Dee said what concerned the community was how many of them with high Pfas levels in their blood have also had health issues that have been known to be associated with Pfas, including cancer.

“It’s been totally ignored by NSW Health … We’ve demanded free blood tests for everyone else.”

Dee said the group was taking a class action against the New South Wales government and Sydney Water.

“The findings of this report clearly are more to do with reducing the legal liability of Sydney Water than actually looking after the health of people in the Blue Mountains,” Dee said.

The panel acknowledged genuine concern in communities about Pfas exposure.

“There is considerable concern, particularly in the Blue Mountains community, about exposure to Pfas through drinking water, and NSW Health takes these concerns very seriously,” Chant said.

“NSW Health will continue to support local clinicians with information for GPs who may be managing patients with concerns about Pfas exposure including evidence about potential adverse health effects, counselling patients, the utility of blood tests for Pfas and the role of further investigations.”

Schistosomiasis is a parasitic infection caused by helminths, a type of worm. Infection occurs during contact with infested water through activities like swimming, washing clothes, and fishing, when larvae penetrate the skin. Surprisingly, the worm often evades detection by the immune system, unlike other bacteria or parasites that typically cause pain, itching, or rashes.

In this new study, researchers from Tulane School of Medicine aimed to find out why the parasitic worm Schistosoma mansoni doesn’t cause pain or itching when it penetrates the skin. Their findings show that S. mansoni causes a reduction in the activity of TRPV1+, a protein that sends signals the brain interprets as heat, pain, or itching. As part of pain-sensing in sensory neurons, TRPV1+ regulates immune responses in many scenarios such as infection, allergy, cancer, autoimmunity, and even hair growth.

The researchers found that S. mansoni produces molecules that suppress TRPV1+ to block signals from being sent to the brain, allowing S. mansoni to infect the skin largely undetected. It is likely S. mansoni evolved the molecules that block TRPV1+ to enhance its survival.

“If we identify and isolate the molecules used by helminths to block TRPV1+ activation, it may present a novel alternative to current opioid-based treatments for reducing pain,” said Dr. De’Broski R. Herbert, Professor of Immunology at Tulane School of Medicine, who led the study. “The molecules that block TRPV1+ could also be developed into therapeutics that reduce disease severity for individuals suffering from painful inflammatory conditions.”

The study also found that TRPV1+ is necessary for initiating host protection against S. mansoni. TRPV1+ activation leads to the rapid mobilization of immune cells, including gd T cells, monocytes, and neutrophils, that induce inflammation. This inflammation plays a crucial role in host resistance to the larval entry into the skin. These findings highlight the importance of neurons that sense pain and itching in successful immune responses

“Identifying the molecules in S. mansoni that block TRPV1+ could inform preventive treatments for schistosomiasis. We envision a topical agent which activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni,” said Dr. Herbert.

In this study, mice were infected with S. mansoi and evaluated for their sensitivity to pain as well as the role of TRPV1+ in preventing infection. Researchers next plan to identify the nature of the secreted or surface-associated helminth molecules that are responsible for blocking TRPV1+ activity and specific gd T cell subsets that are responsible for immune responses. The researchers also seek to further understand the neurons that helminths have evolved to suppress.

Experts at the University of Edinburgh carried out a post-mortem brain examination on 25 cats which exhibited symptoms of dementia in life, including confusion, sleep disruption and an increase in vocalisation, in a bid explore new treatments for humans.

Previously, researchers have studied genetically modified rodents, although the species does not naturally suffer from dementia.

In feline dementia brains, a build-up was found of amyloid-beta, a toxic protein and one of the defining features of Alzheimer’s disease, leading to hopes of a “wonderful” breakthrough due to increased accuracy.

The breakthrough was hailed as a “perfect natural model for Alzheimer’s” by scientists who worked on it.

Microscopy images revealed a build-up of amyloid-beta within synapses of older cats and feline dementia, and scientists hope the findings offer a clearer idea of how amyloid-beta may lead to feline cognitive dysfunction and memory loss, offering a valuable model for studying dementia in people.

Synapses allow the flow of messages between brain cells, and losing these causes reduced memory and thinking abilities in humans with Alzheimer’s.

Researchers found evidence that brain support cells, astrocytes and microglia, engulfed the affected synapses, known as synaptic pruning, an important process during brain development but which contributes to dementia.

Experts believe the findings could contribute to the development of new treatments for Alzheimer’s disease, as well as help to understand and manage feline dementia.

Previously, scientists studying Alzheimer’s relied on genetically modified rodent models. However, studying feline dementia has the potential to help develop human treatments, due to increased accuracy, it is hoped.

The study, funded by Wellcome and the UK Dementia Research Institute, is published in the European Journal of Neuroscience, and included scientists from the Universities of Edinburgh and California, UK Dementia Research Institute and Scottish Brain Sciences.

Dr Robert McGeachan, study lead from the University of Edinburgh’s Royal (Dick) School of Veterinary Studies, said: “Dementia is a devastating disease – whether it affects humans, cats, or dogs. Our findings highlight the striking similarities between feline dementia and Alzheimer’s disease in people.

“This opens the door to exploring whether promising new treatments for human Alzheimer’s disease could also help our ageing pets.

“Because cats naturally develop these brain changes, they may also offer a more accurate model of the disease than traditional laboratory animals, ultimately benefiting both species and their caregivers.”

Professor Danielle Gunn-Moore, personal chair of Feline Medicine at the Royal (Dick) School of Veterinary Studies, said: “Feline dementia is so distressing for the cat and for its person.

“It is by undertaking studies like this that we will understand how best to treat them. This will be wonderful for the cats, their owners, people with Alzheimer’s and their loved ones.

“Feline dementia is the perfect natural model for Alzheimer’s – everyone benefits.”