Mirogabalin: a novel gabapentinoid or another false dawn?

PURPOSE OF REVIEW: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects. RECENT FINDINGS: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking. SUMMARY: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids.

Supportive Psychotherapy Combined with Analgesic Management can Effectively Improve Pain and Quality of Life in Patients with Advanced Prostate Cancer: A Retrospective Study.

OBJECTIVE: Patients with advanced prostate cancer commonly experience psychological issues and have a low quality of life. This study aims to analyse the application of supportive psychotherapy combined with analgesic management on the pain and quality of life of patients with advanced prostate cancer. METHODS: Patients with advanced prostate cancer admitted to our hospital from February 2018 to December 2022 were continuously selected as the research objects. In accordance with the different management methods recorded in the medical record system, the patients were divided into a control group (routine nursing + analgesic management) and an observation group (routine nursing + analgesic management + supportive psychotherapy). The Athens Insomnia Scale (AIS), State Anxiety Scale (S-AI), Trait Anxiety Scale (T-AI), Numeric Rating Scale (NRS) and 36-Item Short-Form Health Survey (SF-36) scores between the two groups were compared. RESULTS: A total of 125 patients with advanced prostate cancer participated in this study, with 60 patients in the control group and 65 patients in the observation group. No significant difference was found in the scores of the AIS, S-AI, T-AI, NRS and SF-36 of the two groups before management (p > 0.05). After management, the AIS (4.00 vs. 5.00, p = 0.002), S-AI (38.88 vs. 41.12, p = 0.002), T-AI (39.17 vs. 41.65, p = 0.001) and NRS (3.00 vs. 3.00, p < 0.001) scores of the observation group were lower than those of the control group. However, the SF-36 scores of the observation group were higher than those of the control group in the dimensions of physiological enginery (75.85 vs. 68.75, p < 0.001), physiological function (71.85 vs. 67.75, p = 0.004), body pain (73.15 vs. 69.33, p = 0.006), social function (73.88 vs. 69.85, p = 0.004), emotional function (72.92 vs. 68.98, p = 0.006), mental health (73.52 vs. 69.83, p = 0.008), vitality (72.09 vs. 69.52, p = 0.044) and general health (70.65 vs. 66.23, p = 0.002). CONCLUSIONS: Supportive psychotherapy combined with analgesic management for patients with advanced prostate cancer may help improve the pain, anxiety and quality of sleep and life of patients.

Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

Protein Kinase A Inhibitor Attenuates the Antinociceptive Effect of NMDA-Receptor Channel Antagonists in the Capsaicin Test in Mice.

Acute nociceptive pain in mice caused by subcutaneous (intraplantar) injection of TRPV1 ion channel agonist capsaicin (1.6 µg/mouse) and the effects of protein kinase A inhibitor H-89 (0.05 mg/mouse, intraplantar injection) and NMDA receptor channel antagonists MK-801 (7.5 and 15 µg/mouse, topical application) and hemantane (0.5 mg/mouse, topical application) on the pain were assessed. MK-801 and hemantane were found to reduce the duration of the pain response. H-89 did not significantly affect the pain in animals, but preliminary administration of this drug abolished the antinociceptive effect of MK-801 (7.5 µg/mouse) and weakens the effect of hemantane (0.5 mg/mouse).

Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia.

AIMS: Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non-opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied. RESULTS: Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor-bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001-10 µg/kg) decreased hyperalgesia in both sexes with similar potency (ED50 = 0.0015 µg/kg) and efficacy. Repeated daily administration of 10 µg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex. CONCLUSION: In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex.

Exploring the Analgesic Initiation Mechanism of Tuina in the Dorsal Root Ganglion of Minor CCI Rats via the TRPV1/TRPA1-cGMP Pathway.

Tuina is a treatment method in traditional Chinese medicine which has analgesic effects and effectively alleviates the symptoms of neuropathic pain (NP). Transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) play major roles in transmitting nociceptive sensory signals in the nociceptive primary sensory dorsal root ganglion (DRG) nerve. The nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate(cGMP) pathway exerts both nociceptive and antinociceptive effects in various chronic pain models. TRPV1 and TRPA1 mediate the influx of calcium, which stimulates the generation of NO. Subsequently, NO activates the NO/cGMP/protein kinase G (PKG) signaling pathway, thereby improving hyperalgesia. In the present study, oa rat model of NP with minor chronic constriction injury (CCI) of the right sciatic nerve of NP was established. The results of behavioral testing showed that, after a one-time tuina intervention, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were prolonged to varying degrees in the tuina group compared with the model group. Similarly, the expression of TRPV1, TRPA1, NO, soluble guanylate cyclase ß (sGCß), cGMP, and PKG1 was significantly decreased in the DRG of the tuina and tuina + TRPV1/TRPA1 antagonist group was significantly decreased. These findings suggest that the tuina intervention can effectively improve the symptoms of thermal and mechanical allodynia caused by peripheral nerve injuries. Tuina exerts immediate analgesic effects through the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

Quantitative analysis of nortriptyline's analgesic properties: a comparative systematic review and meta-analysis.

OBJECTIVES: This study aims to quantitatively analyse nortriptyline's analgesic potency, safety and tolerability. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The systematic search was conducted in Scopus, Web of Science and PubMed in February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical trials evaluating the efficacy of nortriptyline in reducing pain scores (open-label studies and comparisons of nortriptyline with placebo or other analgesics) in different pain types were included. DATA EXTRACTION AND SYNTHESIS: The data extraction procedure and the screening phases were carried out based on predetermined eligibility criteria. To pool the data, the standardised mean difference (SMD) and standardised mean change (SMC) methods, along with random-effect and fixed-effect meta-analysis, were used. The risk of bias was assessed using the Cochrane Collaboration method, and the Grading of Recommendations Assessment, Development and Evaluation criteria were used to measure the certainty of the results. RESULTS: 14 of the initial 648 studies were eventually imported. Nortriptyline was reported to significantly reduce pain severity in chronic low back pain, painful symptoms in major depressive disorder, neuropathy, chronic pelvic pain and neuropathic corneal pain. However, it was not superior to placebo in fibromyalgia and knee osteoarthritis. In comparison to placebo and various alternative analgesics, the pooled SMD for lowering pain scores was 0.43 (0.23-0.64) and -0.18 (-0.39 to 0.03), respectively. In the pretreatment and post-treatment analyses, the pooled SMC was -1.20 (-1.48 to -0.93). Although constipation and xerostomia were the most commonly reported side effects, all references indicated that the adverse events were well tolerated at the administered dosages. CONCLUSION: While nortriptyline is effective in some chronic pains, such as neuropathies, it lacks efficacy in some other chronic pains, such as fibromyalgia and osteoarthritis. Nortriptyline is well tolerated when administered in doses intended for its analgesic effects. Moreover, several studies suggested that the analgesic effects of nortriptyline are comparable to those of amitriptyline and gabapentin.

Pain medication tapering for patients with Persistent Spinal Pain Syndrome Type II, treated with Spinal Cord Stimulation: A RCT-study protocol of the PIANISSIMO study.

BACKGROUND: Spinal Cord Stimulation (SCS) may provide pain relief in patients with therapy-refractory Persistent Spinal Pain Syndrome Type II (PSPS-T2). Despite the evidence that SCS can reduce disability and reduce pain medication usage, only 25% of the patients is able to completely omit pain medication usage after 12 months of SCS. To tackle the high burden of patients who consume a lot of pain medication, tapering programs could be initiated before starting a trajectory with SCS. The current objective is to examine whether a pain medication tapering program before SCS alters disability in PSPS-T2 patients compared to no tapering program. METHODS AND DESIGN: A three-arm, parallel-group multicenter randomized controlled trial will be conducted including 195 patients who will be randomized (1:1:1) to either (a) a standardized pain medication tapering program, (b) a personalized pain medication tapering program, or (c) no tapering program before SCS implantation, all with a follow-up period until 12 months after implantation. The primary outcome is disability. The secondary outcomes are pain intensity, health-related quality of life, participation, domains affected by substance use, anxiety and depression, medication usage, psychological constructs, sleep, symptoms of central sensitization, and healthcare expenditure. DISCUSSION: Within the PIANISSIMO project we propose a way to reduce the risks of adverse events, medication-induced hyperalgesia, tolerance, and dependence by providing pain medication tapering before SCS. Due to the lack of a commonly accepted in-hospital tapering approach, two different tapering programs will be evaluated in this study. If pain medication tapering programs are deemed to be more effective than no tapering on disability, this would add to the evidence towards an improved patient-centered care model in this patient group and set a clear path to advocate for pain medication tapering before SCS as the new standard treatment guideline for these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05861609. Registered on May 17, 2023.

AR71, Histamine H3 Receptor Ligand-In Vitro and In Vivo Evaluation (Anti-Inflammatory Activity, Metabolic Stability, Toxicity, and Analgesic Action).

The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H3R (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H1, H3, and H4 receptors. In in vitro tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models.

Advancements in Non-Addictive Analgesic Diterpenoid Alkaloid Lappaconitine: A Review.

The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors.

German Chamomile (Matricaria chamomilla L.) Flower Extract, Its Amino Acid Preparations and 3D-Printed Dosage Forms: Phytochemical, Pharmacological, Technological, and Molecular Docking Study.

German chamomile (Matricaria chamomilla L.) is an essential oil- containing medicinal plant used worldwide. The aim of this study was to gain knowledge of the phytochemical composition and the analgesic and soporific activity of Matricaria chamomilla L. (German chamomile) flower extract and its amino acid preparations, to predict the mechanisms of their effects by molecular docking and to develop aqueous printing gels and novel 3D-printed oral dosage forms for the flower extracts. In total, 22 polyphenolic compounds and 14 amino acids were identified and quantified in the M. chamomilla extracts. In vivo animal studies with rodents showed that the oral administration of such extracts revealed the potential for treating of sleep disorders and diseases accompanied by pain. Amino acids were found to potentiate these effects. Glycine enhanced the analgesic activity the most, while lysine and ß-alanine improved the soporific activity. The molecular docking analysis revealed a high probability of γ-aminobutyric acid type A (GABAA) and N-methyl-D-aspartate (NMDA) receptor antagonism and 5-lipoxygenase (LOX-5) inhibition by the extracts. A polyethylene oxide (PEO)-based gel composition with the M. chamomilla extracts was proposed for preparing a novel 3D-printed dosage form for oral administration. These 3D-printed extract preparations can be used, for example, in dietary supplement applications.

International Headache Society global practice recommendations for the acute pharmacological treatment of migraine.

BACKGROUND: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. METHODS: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. RESULTS: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. CONCLUSION: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.

Pain Medication and Pain Intensity Following Hip Fractures-Analyses Based on the ProFem Cohort Study.

PURPOSE: Pain is a common symptom following proximal femoral fractures (PFF), however, information on its treatment in terms of agents and type of use (scheduled vs. pro re nata [PRN]) is scarce. The main objective of this study was to examine pain medication regimens according to pain intensity following PFF. Furthermore, we explored the utilization of medication plans. METHODS: The "ProFem"-study on healthcare provision, functional ability, and quality of life after PFF is a German population-based prospective cohort study based on statutory health insurance data and individually linked survey data from different time points including information on the currently used medication. This present analysis refers to the participants' baseline interviews (about 3 months following PFF) conducted from 2018 to 2019 in the participants' private surroundings. RESULTS: The study population comprised 444 participants (mean age: 81.2 years, 71.0% female). Half of them reported high intensity pain, and the mean value for the EuroQol visual analogue scale was 50.8. Most commonly used analgesics were metamizole and tilidine/naloxone. Among participants with high intensity pain, 21.9% received only PRN pain medication and 17.2% no pain medication at all. Overall, 61.5% of participants presented any (printed) medication plan and only 25.2% a "federal standardized medication plan" (BMP). CONCLUSION: As a substantial number of patients reports high intensity pain about 3 months following a PFF, the large proportion of those receiving no or only PRN pain medication raises questions regarding the appropriateness of the therapy. The overall low utilization of the BMP indicates potential for improvement.

Anticancer, anti-inflammatory and analgesic activities of aminoalcohol-based quinoxaline small molecules.

PURPOSE: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. METHODS: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. RESULTS: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1ß and TNF-ß levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. CONCLUSIONS: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.

Orofacial antinociceptive activity of codeine-associated geraniol in mice: a controlled triple-blind study.

This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.

Pain Relief, Functional Recovery, and Chondroprotective Effects of Angelica gigas Nakai in Osteoarthritis Due to Its Anti-Inflammatory Property: An In Vitro and In Vivo Study.

Osteoarthritis (OA), characterized by chronic pain and joint degradation, is a progressive joint disease primarily induced by age-related systemic inflammation. Angelica gigas Nakai (AG), a medicinal plant widely used in East Asia, exhibits promising results for such conditions. This study aimed to evaluate the potential of AG as a drug candidate for modulating the multifaceted pathology of OA based on its anti-inflammatory properties. We evaluated the efficacy of AG in pain relief, functional improvement, and cartilage erosion delay using monosodium iodoacetate-induced OA rats and acetic acid-induced writhing mice, along with its anti-inflammatory effects on multiple targets in the serum and cartilage of in vivo models and lipopolysaccharide-stimulated RAW 264.7 cells. In vivo experiments demonstrated significant analgesic and chondroprotective effects of AG, along with functional recovery, in model animals compared with the active controls. AG dose-dependently modulated inflammatory OA pathology-related targets, including interleukin-1ß, tumor necrosis factor-α, matrix metalloproteinase-13, and cyclooxygenase-2, both in vitro and in vivo. In conclusion, AG could be a potential drug candidate for modulating the multifaceted pathology of OA. Nevertheless, further comprehensive investigations, involving a broader range of compounds, pathologies, and mechanisms, are warranted to validate these findings.

Efficacy of preoperative and postoperative medications in reducing pain after non-surgical root canal treatment: an umbrella review.

OBJECTIVE: This study analyzed, using an umbrella review, existing systematic reviews on medications to prevent and control postoperative endodontic pain to guide professionals in choosing the most effective drug. MATERIALS AND METHODS: An electronic search in the PubMed (MEDLINE), LILACS, SciELO, EMBASE, Scopus, Web of Science, Cochrane Reviews, and Data Archiving and Networked Services (DANS) databases retrieved 17 systematic reviews. The study included only systematic reviews of clinical trials with or without meta-analyses evaluating effectiveness of medications in reducing pain after non-surgical endodontic treatment. RESULTS: The evidence showed that steroidal and non-steroidal anti-inflammatory drugs and opioids effectively controlled pain within six to 24 h. CONCLUSIONS: Dexamethasone, prednisolone, paracetamol, and mainly ibuprofen provided higher postoperative pain relief. The quality of evidence of the reviews ranged from very low to high, and the risk of bias from low to high, suggesting the need for well-designed clinical trials to provide confirmatory evidence. CLINICAL RELEVANCE: This review emphasizes the efficacy of developing protocols for pain control after endodontic therapy.

The Anti-Inflammatory, Analgesic, and Antioxidant Effects of Polyphenols from Brassica oleracea var. capitata Extract on Induced Inflammation in Rodents.

This study investigates the anti-inflammatory, analgesic, and antioxidant properties of polyphenols extracted from Brassica oleracea var. capitata (cabbage) ethanolic extract (BOE). Given the historical use of cabbage in traditional medicine for treating various ailments, this research aims to validate these effects scientifically. The study involved the characterization of BOE's bioactive compounds using Fourier Transform Infrared Spectroscopy (FTIR) and Liquid Chromatography-Diode Array Detection-Electro-Spray Ionization Mass Spectrometry (HPLC-DAD-ESI MS) analysis. We assessed the anti-inflammatory and analgesic effects of topical and oral BOE administration on rodent models with acute and subacute inflammation. Additionally, the antioxidant capacity of orally administered BOE was evaluated. The results showed that BOE possesses significant levels of phenolic compounds with a potent antioxidant activity. The topical administration of BOE demonstrated notable anti-inflammatory effects in the tested rodent models, which were comparable with nonsteroidal anti-inflammatory drugs. These findings suggest that BOE could be a valuable natural remedy for inflammation-related conditions, supporting its traditional uses and highlighting its potential for further pharmacological development.

Ketamine for Pain in Hospice Patients - A Transdermal Gel Applied to the Painful Site.

The author has been using ketamine to treat hospice patients for several years, with varying degrees of success, and reports being most successful with the transdermal-gel form. He has also had success with ketamine administered as a nasal spray. In addition to providing general comments on the use of ketamine in this context, he presents four brief case reports demonstrating the use of ketamine and other medications in treating pain associated with various types of cancer.