Search Results (2,034)

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Background: Pain is a multifaceted and debilitating symptom in patients with gastrointestinal cancer, especially those undergoing surgical resection followed by chemotherapy. The interplay between inflammatory, neuropathic, and psychosocial components often renders conventional analgesia insufficient. Psychobiotics—probiotic strains with neuroactive properties—have recently emerged as potential modulators of pain perception through neuroimmune and gut–brain axis pathways. Methods: This post hoc analysis is based on the ProDeCa randomized, placebo-controlled trial, which originally aimed to assess the psychotropic effects of a four-strain psychobiotic formulation in postoperative gastrointestinal cancer patients receiving chemotherapy. In the current analysis, we evaluated changes in pain perception among non-depressed and depressed participants, who received either psychobiotics or placebo, along with standard analgesic regimes. Pain was assessed at baseline, after a month of treatment, and at follow-up, 2 months thereafter, using the Short-Form McGill Pain Questionnaire (SF-MPQ), capturing both sensory and affective components, as well as with the Present Pain Intensity and the VAS scores. Results: Psychobiotic-treated participants—particularly the non-depressed ones—exhibited a significant reduction in both quantitative and qualitative pain indices over time compared with placebo-treated ones. Improvements were noted in total pain rating index scores, sensory and affective subscales, and present pain intensity. These effects were sustained up to 2 months after intervention. In contrast, placebo groups demonstrated worsening in pain scores, probably influenced by ongoing chemotherapy and disease progression. The analgesic effect was less pronounced but still observable in the subgroup with symptoms of depression. Conclusions: Adjunctive psychobiotic therapy appears to beneficially modulate pain perception in gastrointestinal oncology patients receiving chemotherapy, with the most pronounced effects being in non-depressed individuals. These findings suggest psychobiotics as a promising non-opioid add-on for comprehensive cancer pain management and support further investigation in larger pain-targeted trials. Full article

In this perspective article, we introduce Ecocebo as a novel concept describing the modulatory effects of physical environments, whether natural or built, on drug effect. Positioned as a spatial component of the placebo effect, Ecocebo is grounded in evidence-based design principles and proposes that environmental features such as natural light, greenery, spatial geometry, and calming esthetics can significantly influence sensory, emotional, and cognitive processes. These environmental factors may enhance or modify pharmacological responses, especially for analgesics, anxiolytics, and antidepressants. We highlighted how exposure to restorative spaces can reduce pain perception, stress, and the need for medication, paralleling findings in placebo research where contextual and sensory cues influence brain regions linked to emotion and pain regulation. We propose virtual reality (VR) as the most suitable methodological tool to study Ecocebo in controlled and ecologically valid settings. VR allows for the precise manipulation of spatial features and real-time monitoring of physiological and psychological responses. We also propose integrating VR with neuromodulation techniques to investigate brain–environment–drug interactions. Finally, we addressed key methodological challenges such as defining control conditions and standardizing the measurement of presence. This perspective opens new directions for the integration of non-pharmacological and pharmacological interventions and personalized therapeutic environments to optimize clinical outcomes. Full article

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

Background and Aims: This study explored the feasibility of performing intestinal reconstruction after enterostomy in infants using ultrasound-guided epidural anesthesia with sedation, aiming to avoid invasive airway manipulation and the use of opioids. Methods: We included twenty infants scheduled for intestinal reconstruction in this prospective case series. Success was defined by the absence of additional general anesthesia and invasive airway management. The secondary endpoints were the need for additional intraoperative anesthetic and analgesic drugs and postoperative analgesics in the recovery room. The study was approved by the Ethics Commission at the Medical University of Vienna (ref. 1133/2017, approval date 24 August 2017) and registered in the German Clinical Trial Register (DRKS ID: DRKS00012683, approval date 15 July 2019). Results: Nineteen out of twenty procedures were successfully performed with epidural anesthesia under spontaneous breathing and without airway manipulation; one child required endotracheal intubation due to an unexpected, extensive surgical procedure. No child needed systemic analgesics in the recovery room. Conclusions: Epidural anesthesia with sedation can effectively minimize airway manipulation and reduce general anesthesia requirements for intestinal reconstruction in infants. Full article

Chronic, low-grade inflammation is a key contributor to the development of numerous non-communicable diseases (NCDs), including cardiovascular, metabolic, and neurodegenerative disorders. Conventional anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, often present safety concerns with prolonged use, highlighting the need for safer, multi-targeted therapeutic options. Iridoids, a class of monoterpenoid compounds abundant in several medicinal plants, have emerged as promising bioactive agents with diverse pharmacological properties. They exert anti-inflammatory and metabolic regulatory effects by modulating key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR) pathways. This review provides a comprehensive summary of the major iridoid metabolites derived from ten Bulgarian medicinal plant species, along with mechanistic insights from in vitro and in vivo studies. Documented biological activities include anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, organoprotective, antibacterial, antiviral, analgesic, and metabolic effects. By exploring their phytochemical profiles and pharmacodynamics, we underscore the therapeutic potential of iridoid-rich Bulgarian flora in managing inflammation-related and metabolic diseases. These findings support the relevance of iridoids as complementary or alternative agents to conventional therapies and highlight the need for further translational and clinical research. Full article

Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that can adversely affect patients’ quality of life (QoL) and adherence to therapy. Commonly reported side effects include vasomotor symptoms, such as hot flashes; musculoskeletal disorders, such as arthralgia and myalgia; mood disorders; and genitourinary discomfort, such as vaginal dryness and dyspareunia. Additionally, AIs are associated with a heightened risk of bone loss, leading to osteoporosis and fractures, and may have implications for cardiovascular health. Effective management of these adverse events is pivotal in maintaining treatment adherence and preserving QoL. Evidence-based strategies to address these toxicities include pharmacological interventions, such as analgesics for joint pain, bisphosphonates or denosumab for bone health, and hormonal or non-hormonal approaches for vasomotor and genitourinary symptoms. Non-pharmacological measures, including physical activity, dietary adjustments, and complementary therapies, can also help mitigate symptoms. This review examines the broad spectrum of AI-associated toxicities, discusses their clinical implications, and provides an overview of evidence-based management strategies. These insights aim to support clinicians in optimizing patient care while minimizing the toxicities of therapy. Full article

Background/Objectives: Laparoscopic appendectomy (LsA) is a standard acute surgical procedure typically performed under general anesthesia (GA). However, GA is associated with side effects such as hemodynamic instability and postoperative nausea/vomiting. Regional anesthesia (RA) has gained attention as an effective alternative in such surgeries, as it reduces surgical stress responses, provides adequate postoperative analgesia, and promotes early mobilization. This study evaluates the effectiveness of the combined use of spinal anesthesia (SA) and transversus abdominis plane block (TAPB) in LsA procedures. Methods: This retrospective observational study included 220 patients who underwent LsA between 2020 and 2023. Patients were divided into two groups: Group 1 (n = 110) received bilateral TAPB, and Group 2 (n = 110) received unilateral TAPB, both under SA. Postoperative pain was assessed using the Visual Analog Scale (VAS), and outcomes such as time to first analgesic requirement, analgesic consumption, and patient satisfaction were recorded. Results: This study evaluated the effects of SA combined with TAPB in LsA. Bilateral TAPB significantly prolonged the time to first analgesic request (13.7 vs. 12.1 h; p = 0.001) and reduced analgesic requirements (p = 0.008) compared to unilateral TAPB. VAS scores were significantly lower in Group 1 at the 9th and 12th hours postoperatively (p = 0.003 and p = 0.039). Although overall satisfaction scores were similar, a higher proportion of patients in Group 1 reported being “very satisfied” or “excellent” (55.5% vs. 42.7%). Conclusions: The combination of spinal anesthesia and bilateral TAPB is a safe and effective anesthetic strategy for LsA. Compared to unilateral TAPB, it offers superior postoperative analgesia and improved patient satisfaction. Full article

Introduction: Postoperative pain management is complex and crucial in major gynecology oncological surgery. Currently, there is no well-defined standardized approach, resulting in significant variability in practices worldwide. This systematic review evaluates the effectiveness of analgesic strategies used postoperatively in gynecological cancer surgery. Methods: A systematic review was conducted from inception to June 26th 2024 to identify all randomized controlled trials (RCTs) assessing pain management following any surgery for gynecological cancer. This was performed on the CENTRAL, PubMed, Embase, and MEDLINE databases. Results: A total of 46 RCTs met the inclusion criteria. Of these 5316 patients, 1844 patients had cervical cancer, 99 had endometrial cancer, and 158 had ovarian cancer. The remaining 3215 participants had unspecified gynecological cancers or benign pathology. No studies focused on postoperative analgesia for vulval cancer. A meta-analysis was not feasible due to heterogeneity in study design, analgesic interventions (i.e., opioids, local anesthetics, paracetamol, NSAIDs, and holistic and complementary therapies), and multiple routes of administration (i.e., oral, parenteral, regional, neuraxial, local infiltration, intraperitoneal, intramuscular, patient-controlled, topical, and rectal). No single analgesic modality demonstrated clear superiority. The median Jadad score for methodological quality of the included trials was 4. Conclusions: The limited cancer-specific RCTs and diversity of analgesia modalities utilized reflect the wide range of applications. Postoperative pain is multifactorial and cannot be adequately managed with a single agent. National and international guidelines should aim to establish a standardized framework for postoperative pain management in gynecological cancers, ensuring accessible, evidence-based care that enhances both short- and long-term patient quality of life. Full article

Paracetamol (PAR) is a common antipyretic and analgesic extensively used to treat cold and flu symptoms. It has been proven to be effective in headaches and relieving fever and pain. It is usually found as an over-the-counter drug, which has been associated with an increase in cases of poisoning due to overdose. Therefore, the development of new analytical tools for the detection of PAR at low concentrations in different samples is necessary. In this work, a Molecularly Imprinted Polymer (MIP)-based electrochemical sensor was designed for the selective and sensitive determination of PAR using a glassy carbon electrode (GCE) modified with a polymeric film obtained through the electropolymerization of o-aminophenol. A complete characterization based on electrochemical techniques, such as electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), and scanning electron microscopy (SEM) was used to examine all steps involved in the construction of the MIP-based electrochemical sensor. In addition, all parameters affecting the MIP were optimized. As a result, the MIP-based electrochemical sensor showed a very low limit of detection (LOD) of 10 nM, with an analytical sensitivity of (3.4 ± 0.1) A M⁻¹. In addition, construction of the MIP-based electrochemical sensor showed highly reproducibility, expressed in terms of a variation coefficient lower than 4%. The MIP-based electrochemical sensor was successfully used in an assay for the determination of PAR in pharmaceutical products. The performance of the MIP-based electrochemical sensor was compared to High Performance Liquid Chromatography (HPLC) for the determination of PAR in pharmaceutical samples, showing excellent agreement between the two methodologies. A very important aspect of the developed sensor was its reusability for at least twenty times. The MIP-based electrochemical sensor is a reliable analytical tool for the determination of PAR. Full article

There is growing evidence regarding non-pharmacological therapies such as music as a supportive approach for the treatment of various clinical conditions in humans. Physiological and neurobiological research suggests that music exposure is related to endorphin, endocannabinoid and dopamine release, favourable effects on autonomic nervous system functioning and is associated with decreased pain perception and reduced stress response. Further evidence in humans demonstrates a beneficial role of music application during the perioperative period by improving various outcome measures, such as the perioperative stress and anxiety levels, the sedation or general anaesthetic requirements, the pain levels, the analgesic requirements and other parameters related to patient prognosis, without reported side effects. Accordingly, such interventions have been considered as a method of environmental enrichment for animal welfare enhancement, by masking potentially disturbing background noises and by ameliorating anxiety or aggressive behaviours in different stressful settings in dogs and cats. Furthermore, research has been lately extended to the potential music’s effect in these species during the perioperative period, considered a stressful setting, as well. This review presents the existing evidence of music application focusing on the perioperative period of dogs and cats, as part of a multimodal approach, to improve their surgical outcome and welfare. Full article

Background/Objectives: Intravenous patient-controlled analgesia (IV-PCA) is commonly used for pain control following arthroscopic rotator cuff repair (ARCR), but its use is limited by adverse effects such as nausea and vomiting. The suprascapular nerve block (SSNB) has emerged as an effective regional analgesic alternative. This retrospective cohort study aimed to compare the analgesic efficacy and safety of continuous intra-operative suprascapular nerve block (CI-SSNB) alone versus CI-SSNB combined with fentanyl-based IV-PCA (CI-SSNB + IV-PCA). Methods: A total of 40 patients undergoing ARCR under general anesthesia with a single-shot interscalene block (ISB) were allocated to either CI-SSNB alone (n = 20) or CI-SSNB + IV-PCA (n = 20). Pain scores were assessed using a 0–10 visual analog scale from 0 to 72 h postoperatively at predetermined intervals, along with opioid consumption and adverse events. Results: At post-operative day 0 (POD 0, 10 p.m.), mean pain scores were 5.75 ± 2.59 in the CI-SSNB + IV-PCA group vs. 3.95 ± 3.00 in the CI-SSNB group (p = 0.050). The total number of rescue pethidine doses up to post-operative day 3 was 1.80 ± 2.02 vs. 0.95 ± 1.10, respectively (p = 0.108). However, adverse effects such as nausea and vomiting occurred only in the CI-SSNB + IV-PCA group. Conclusions: CI-SSNB provides comparable analgesia to CI-SSNB + IV-PCA, while avoiding IV-PCA-related side effects, suggesting that IV-PCA may not be necessary when CI-SSNB is employed for post-operative analgesia following ARCR. Full article

Background: Chronic musculoskeletal pain (CMP) is a multidimensional condition involving both peripheral and central mechanisms, with increasing evidence supporting an interplay between subjective pain perception and autonomic nervous system (ANS) function. However, few studies have explored whether a single non-invasive intervention can concurrently modulate both domains. Objectives: To evaluate the short-term effects of a single session of Pulsed Electromagnetic Field (PEMF) therapy—administered via the PAP Ion Magnetic Induction (PAPIMI™) device—on subjective pain intensity and heart rate variability (HRV) parameters in individuals with CMP. The relationship between perceived pain relief and physiological autonomic adaptations was also explored. Methods: Thirty adults with CMP underwent a single PAPIMI™ session. Subjective pain intensity was measured using the Numeric Pain Rating Scale (NPRS), while autonomic function was assessed via HRV. Pre- to post-intervention changes were analyzed using the Wilcoxon Signed-Rank test, while Spearman’s correlation was computed to assess associations between post-intervention changes in subjective perceived pain and HRV parameters. Results: A significant reduction in NPRS scores (p < 0.001) was found after PAPIMI intervention. Also, a significant increase in specific parasympathetic-related HRV indices, namely, RMSSD (p = 0.015) and HF power (p = 0.029), was observed. No significant correlations were found between post-intervention changes in pain perception and HRV metrics. Conclusions: A single PAPIMI session induced both analgesic effects and improvements in autonomic balance in individuals with CMP. These findings underscore the potential of PAPIMI as a non-pharmacological approach for rapid pain modulation and systemic rebalancing. Full article

Background/Objectives: Pain is a growing public health concern worldwide, and the use of combinations of drugs can improve their analgesic effects while minimizing their adverse effects. Drugs such as metformin (antidiabetic) and melatonin (sleep regulator) have analgesic potential in combination. In this study, we evaluated the pharmacological interaction between metformin and melatonin when orally administered in a rat model, using the formalin test. Methods: Female Wistar rats (220–350 g) were injected with 50 µL of 1% formalin in the dorsal surface of the right hind paw. Formalin produces pain-related flinching behavior, and antinociception was evaluated as the reduction in this response. The percentage of the antinociceptive effect was determined after the oral administration of metformin (30–1000 mg/kg), melatonin (10–150 mg/kg), and their combination (MMC). To establish the nature of the interaction, isobolographic analysis was performed in a fixed-dose ratio (0.5:0.5), based on the effective dose 50 (ED₅₀) values for each drug: metformin (947.46 ± 242.60 mg/kg) and melatonin (126.86 ± 37.98 mg/kg). To evaluate the mechanism of action, the receptor antagonist for metformin compound C (dorsomorphin) for AMPK inhibition, MT1 and MT2 melatonin receptor antagonists (4-P-PDOT, luzindole), and an opioid antagonist (naloxone) were employed. The rotarod test was used to evaluate the safety profile of the combination. Results: The metformin–melatonin combination significantly reduced the number of flinches in the second phase of the formalin test. The theoretical ED₅₀ for the combination (ED₅₀ T) was 537.15 ± 122.76 mg/kg. Experimentally, the ED₅₀ (ED₅₀ E) was significantly lower (360.83 ± 23.36 mg/kg), indicating a synergistic interaction for the combination involving opioidergic pathways, MT2 receptors, and AMPK activation. Conclusions: Oral metformin–melatonin coadministration could provide a therapeutic alternative for inflammatory pain. Full article