Search Results (56)

The search for effective pain management solutions remains a critical challenge, especially amidst growing concerns over the use of conventional opioids. In the US, opioid-related mortality rates have surged to as many as 80 deaths per 100,000 people in some states, with an estimated economic burden of USD 1.5 trillion annually—exceeding the gross domestic product (GDP) of most US industrial sectors. A remarkable breakthrough lies in the discovery that indole and oxindole alkaloids, produced by several genera within the plant Tribe Naucleeae, act on opioid receptors without activating the beta-arrestin-2 pathway, the primary driver of respiratory depression and overdose deaths. This systematic review explores the pharmacological properties, mechanisms of action, dosing considerations, interactions, and long-term effects of mitragynine and corynoxeine, alkaloids from the Southeast Asian plant Mitragyna speciosa (kratom) and others in the Tribe Naucleeae. Mitragynine, a partial opioid receptor agonist, and corynoxeine, known for its anti-inflammatory and neuroprotective effects, demonstrate significant therapeutic potential for managing diverse pain types—including neuropathic, inflammatory, nociceptive, visceral, and central pain syndromes—with a focus on cancer pain. Unlike traditional opioids, these compounds do not recruit beta-arrestin-2, avoiding key adverse effects such as respiratory depression, severe constipation, and rapid tolerance development. Their distinct pharmacological profiles make them innovative candidates for safer, non-lethal pain relief. However, challenges persist, including the unregulated nature of kratom products, inconsistencies in potency due to crude extract variability, potential for misuse, and adverse drug interactions. Addressing these issues requires establishing standardized quality control protocols, such as Good Manufacturing Practices (GMP), to ensure consistent potency and purity. Clear labeling requirements with dosage guidelines and warnings should be mandated to ensure safe use and prevent misuse. Furthermore, the implementation of regulatory oversight to monitor product quality and enforce compliance is essential. This review emphasizes the urgency of focused research to optimize dosing regimens, characterize the pharmacodynamic profiles of these alkaloids, and evaluate long-term safety. By addressing these gaps, the mitragynine- and corynoxeine-related drug classes can transition from promising plant-derived molecules to validated pharmacotherapeutic agents, potentially revolutionizing the field of pain management. Full article

The nasal cavity has become a focal point for drug delivery research. Beyond its use in treating local diseases, the nasal route is appealing due its ability to deliver systemically potent drugs with low oral bioavailability. Recent interest in nasal vaccination has driven significant pre-clinical and clinical advancements. Further R&D holds promise for expanding nasal medications, offering innovative healthcare solutions. This review explores strategies using polysaccharides to enhance nasal delivery of hydrophilic drugs, peptides, proteins, genes, and other active compounds that typically struggle to permeate the nasal epithelium. Polysaccharides are attractive excipients due to their potential to enhance nasal absorption, regulate drug release, and extend residence time in the nasal cavity through bioadhesive properties. Studies on their mechanisms affecting drug absorption, potential toxicities, and applications will also be reviewed considering the particularities of nasal epithelium anatomy and physiology. Most products with these excipients are in pre-clinical and clinical evaluation, but PecFent, a pectin-based formulation, is approved for nasal administration of opioids for breakthrough cancer pain, offering faster pain relief and a better benefit–risk ratio due to pectin. Other polysaccharides like chitosan, cyclodextrins, hyaluronic acid, and alginate have shown potential in enhancing nasal drug absorption. This approach also holds promise for enhancing drug transport from the nasal cavity to the CNS (nose-to-brain), potentially advancing treatments for neurodegenerative diseases. Full article

Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc’s location, compartmentalization, hypovascularization and delicate physiological environment. Furthermore, the imaging modalities currently used in practice are largely unable to accurately identify sources of pain ostensibly discogenic in origin. These obstacles are considerable; however, recent research has begun to shed light on possible breakthrough technologies. Such breakthroughs include revolutionary imaging to better identify tissue sources of pain. Furthermore, novel molecular therapies have been shown to be able to mediate the progression of degenerative disc disease in some large animal studies, and even provide some insight into suppressing the development of tissue sources of discogenic pain. These potential breakthrough technologies have yet to be translated for clinical use. Full article

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health. Full article

Background/Objectives: Rhomboid intercostal block (RIB) is a new interfascial plane block. RIB is a simple and clinically effective technique. Paravertebral block (PVB) is offered as a first-line regional anesthesia technique for thoracoscopic surgeries. In this study, we aim to compare the analgesic efficacy of RIB to PVB in video-assisted thoracoscopic surgeries (VATSs). Methods: This is a prospective randomized study with 84 patients aged 18–75 and ASA I–III, undergoing VATS for primary lung cancer. The study was approved by an ethical committee and registered under clinicaltrials.org. With informed consent, patients were randomized to receive ultrasound-guided RIB or PVB at T5-level with 20 mL of %0.25 bupivacaine preoperatively. Surgeries were performed under general anesthesia. Postoperatively, patient-controlled IV fentanyl analgesia was prescribed, delivering 10 μg boluses upon request with 10 min of a lock-out period. Patients received paracetamol 1 g IV three times a day and tramadol 50 mg IV for breakthrough pain. The postoperative Numeric Rating Scale (NRS) for pain, total opioid consumption, and rescue analgesic requirements were recorded postoperatively at 1, 3, 6, 12, and 24 h. Results: There were no significant differences in 24 h total opioid consumption between the RIB and PVB groups [PVB: 48.5 (39.5–55) mcg; RIB: 48.6 (40.2–65) mcg; p = 0.258], nor in rescue analgesic requirements [PVB: seven patients (20%); RIB: seven patients (17.1%); p = 0.570]. NRS pain scores were also similar between the groups, with no significant difference in overall pain control efficacy (p = 0.833). Conclusions: RIB is comparable to PVB in analgesic efficacy for VATS and can be considered as an alternative analgesic modality. Full article

Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy’s transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential. Full article

Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions. Full article

Infants, children and young people with life-limiting or life-threatening conditions often experience acute, transient pain episodes known as breakthrough pain. There is currently no established way to assess breakthrough pain in paediatric palliative care. Anecdotal evidence suggests that it is frequently underdiagnosed and undertreated, resulting in reduced quality of life. The development of a standardised paediatric breakthrough pain assessment, based on healthcare professionals’ insights, could improve patient outcomes. This study aimed to explore how healthcare professionals define and assess breakthrough pain in paediatric palliative care and their attitudes towards a validated paediatric breakthrough pain assessment. This was a descriptive qualitative interview study. Semi-structured interviews were conducted with 29 healthcare professionals working in paediatric palliative care across the UK. An inductive thematic analysis was conducted on the data. Five themes were generated: ‘the elusive nature of breakthrough pain’, ‘breakthrough pain assessment’, ‘positive attitudes towards’, ‘reservations towards’ and ‘features to include in’ a paediatric breakthrough pain assessment. The definition and assessment of breakthrough pain is inconsistent in paediatric palliative care. There is a clear need for a validated assessment questionnaire to improve assessment, diagnosis and management of breakthrough pain followed by increased healthcare professional education on the concept. Full article

The measurement of partial pressures of oxygen (O₂) and carbon dioxide (CO₂) is fundamental for evaluating a patient’s conditions in clinical practice. There are many ways to retrieve O₂/CO₂ partial pressures and concentrations. Arterial blood gas (ABG) analysis is the gold standard technique for such a purpose, but it is invasive, intermittent, and potentially painful. Among all the alternative methods for gas monitoring, non-invasive transcutaneous O₂ and CO₂ monitoring has been emerging since the 1970s, being able to overcome the main drawbacks of ABG analysis. Clark and Severinghaus electrodes enabled the breakthrough for transcutaneous O₂ and CO₂ monitoring, respectively, and in the last twenty years, many innovations have been introduced as alternatives to overcome their limitations. This review reports the most recent solutions for transcutaneous O₂ and CO₂ monitoring, with a particular consideration for wearable measurement systems. Luminescence-based electronic paramagnetic resonance and photoacoustic sensors are investigated. Optical sensors appear to be the most promising, giving fast and accurate measurements without the need for frequent calibrations and being suitable for integration into wearable measurement systems. Full article

Regional anesthesia has shown to be successful in controlling major pain in trauma patients. However, the possibility of masking acute compartment syndrome (ACS) after peripheral nerve blocks for limb injuries is still controversially discussed. Therefore, we aimed to summarize the current literature regarding this topic to shed light on the impact of peripheral regional anesthesia on the diagnosis of ACS in trauma patients. We searched Pubmed, Google Scholar and the Cochrane Library for literature following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The analysis of these reports was included in the context of the current literature concerning this topic. We found no (randomized) studies, and only six case reports dealing with the impact of peripheral nerve blocks and ACS in patients after a limb trauma met our criteria and were included in our review. Only one reported a delay in the diagnosis of ACS. In most of the cases (5 of 6), the breakthrough pain, despite the nerve block, proved to be a good indicator of a developing ACS. However, despite some narrative articles about the topic including some recommendations about the possibly safe use of regional anesthesia techniques for limb trauma, there is still no international consensus and only one national guideline focusing on the possibly safe use of peripheral nerve blocks in trauma patients at risk of ACS. After reviewing the respective literature, we consider that intra-articular analgesia, sensory blocks, fascial plane blocks and low-concentration continuous peripheral nerve blocks are effective for analgesia and a low-risk analgesia tool for trauma and postsurgical patients at risk of ACS due to the fact that they do not lead to a dense block. Finally, we summarized suggestions based on the results of the literature for the different regional anesthesia modalities in these patients in a table to facilitate the use of these techniques. Full article

Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients’ quality of life. Patients with DNP often experience spontaneous pain and evoked pain such as mechanical allodynia and thermal hyperalgesia, meaning that their physical and psychological health are severely impaired. Unfortunately, the mechanisms of DNP remain highly elusive, so substantial breakthrough in effective DNP targeted treatments is still clinically challenging. This article will hence summarise the main mechanisms currently known to underlie DNP pathogenesis, along with describing some of the current and potential treatment methods against diabetic neuropathic pain. Full article

Background: Our aim was to examine the frequency and prescription pattern of breakthrough (BTO) and scheduled (SCH) opioids and their ratio (BTO/SCH ratio) of use, prior to and after referral to an inpatient supportive care consult (SCC) for cancer pain management (CPM). Methods and Materials: Patients admitted at the MD Anderson Cancer Center and referred to a SCC were retrospectively reviewed. Cancer patients receiving SCH and BTO opioids for ≥24 h were eligible for inclusion. Patient demographics and clinical characteristics, including the type and route of SCH and BTO opioids, daily opioid doses (MEDDs) of SCH and BTO, and BTO/SCH ratios were reviewed in patients seen prior to a SCC (pre-SCC) and during a SCC. A normal BTO ratio was defined as 0.5–0.2. Results: A total of 665/728 (91%) patients were evaluable. Median pain scores (p < 0.001), BTO MEDDs (p < 0.001), scheduled opioid MEDDs (p < 0.0001), and total MEDDs (p < 0.0001) were higher, but the median number of BTO doses was fewer (2 vs. 4, p < 0.001), among patients seen at SCC compared to pre-SCC. A BTO/SCH ratio over the recommended ratio (>0.2) was seen in 37.5% of patients. The BTO/SCH ratios in the pre-SCC and SCC groups were 0.10 (0.04, 0.21) and 0.17 (0.10, 0.30), respectively, p < 0.001. Hydromorphone and Morphine were the most common BTO and SCH opioids prescribed, respectively. Patients in the early supportive care group had higher pain scores and MEDDs. Conclusions: BTO/SCH ratios are frequently prescribed higher than the recommended dose. Daily pain scores, BTO MEDDs, scheduled opioid MEDDs, and total MEDDs were higher among the SCC group than the pre-SCC group, but the number of BTO doses/day was lower. Full article

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients’ quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation. Full article

Cardiovascular diseases (CVDs) are a group of diseases with a very high rate of morbidity and mortality. The clinical presentation of CVDs can vary from asymptomatic to classic symptoms such as chest pain in patients with myocardial infarction. Current therapeutics for CVDs mainly target disease symptoms. The most common CVDs are coronary artery disease, acute myocardial infarction, atrial fibrillation, chronic heart failure, arterial hypertension, and valvular heart disease. In their treatment, conventional therapies and pharmacological therapies are used. However, the use of herbal medicines in the therapy of these diseases has also been reported in the literature, resulting in a need for critical evaluation of advances related to their use. Therefore, we carried out a narrative review of pharmacological and herbal therapeutic effects reported for these diseases. Data for this comprehensive review were obtained from electronic databases such as MedLine, PubMed, Web of Science, Scopus, and Google Scholar. Conventional therapy requires an individual approach to the patients, as when patients do not respond well, this often causes allergic effects or various other unwanted effects. Nowadays, medicinal plants as therapeutics are frequently used in different parts of the world. Preclinical/clinical pharmacology studies have confirmed that some bioactive compounds may have beneficial therapeutic effects in some common CVDs. The natural products analyzed in this review are promising phytochemicals for adjuvant and complementary drug candidates in CVDs pharmacotherapy, and some of them have already been approved by the FDA. There are insufficient clinical studies to compare the effectiveness of natural products compared to approved therapeutics for the treatment of CVDs. Further long-term studies are needed to accelerate the potential of using natural products for these diseases. Despite this undoubted beneficence on CVDs, there are no strong breakthroughs supporting the implementation of natural products in clinical practice. Nevertheless, they are promising agents in the supplementation and co-therapy of CVDs. Full article

Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 (p = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, p < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief. Full article