Abstract: Background: Although upper and lower respiratory tract diseases coexist, studies discussing the relationship between chronic rhinitis (CR) and chronic obstructive pulmonary disease (COPD) are limited. Fluticasone nasal sprays are common treatment options for patients with rhinitis. Therefore, we aimed to investigate the effects of fluticasone nasal spray on patients with both CR and COPD. Methods: A retrospective review was performed using data from former smokers with CR and COPD at China Medical University Hospital (CMUH). Based on their medication history, patients were allocated into Group A, who had received treatment with fluticasone nasal spray, and Group B, who had never received this treatment. Pulmonary function test results, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were collected for both groups before treatment and one year after treatment. Statistical analysis was performed to evaluate the impact of fluticasone nasal spray treatment on pulmonary function. Results: A total of 123 former smokers were included, with 62 patients in Group A and 61 patients in Group B. At the baseline, there was no significant difference in age, sex, and pulmonary function between the two groups. After one year of treatment, Group A showed an upward trend in pulmonary function, with FEV1 increasing from 1.613 ± 0.554 to 1.708 ± 0.675 (P < 0.05) and FVC increasing from 2.540 ± 0.694 to 2.670 ± 0.839 (P < 0.05). Whereas, Group B exhibited a downward trend in pulmonary function after one year, with FEV1 decreasing from 1.609 ± 0.554 to 1.544 ± 0.517 (P < 0.05) and FVC decreasing from 2.586 ± 0.665 to 2.495 ± 0.679 (P < 0.05). Conclusions: The use of fluticasone nasal spray can improve pulmonary function in former smokers with both CR and COPD. This finding supports the "one airway, one disease" theory.

Abstract: This study aimed to elucidate the pathological features of thrombus-associated amyloid deposition. Thes features were validated by immunohistochemistry combined with proteomic analyses using liquid chromatography–tandem mass spectrometry with laser microdissection. Our findings revealed that thrombus-associated amyloid deposits within the thrombus and vessel wall primarily comprised apolipoprotein A-I, with a mixture of amyloid fibrils derived from amyloidogenic proteins, including transthyretin and lactoferrin. Given that these proteins are present in the blood, our results support a previous hypothesis that is, proteins denatured during thrombus aging are a source of amyloid. Furthermore, phagocytes were infiltrated around the intramural and extravascular deposits rather than around the amyloid deposits within the thrombus. Therefore, amyloid deposits generated within the thrombus may be transported from regions with limited blood flow to the vessel wall and surrounding tissues, where blood flow is present, during thrombus processing. These deposits were primarily removed by phagocytic cells. Our results suggest that a facilitative effect on deposition occurs via a cross-seeding mechanism between amyloid fibrils and that phagocytes can remove amyloid deposits. These findings help elucidate the pathogenesis of localized amyloidosis.

Abstract: Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analysed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified “completed suicide” (β = 0.35) and “product use for unknown indication” (β = 0.33) as the strongest predictors of fatal outcomes. Age revealed a modest negative association with fatal outcome (β = -0.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. It is here suggested tat clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine.

Abstract: Background: Periodontal disease and gingival inflammation are globally highly prevalent and may entail distal consequences on systemic health. While professional mechanical plaque removal (PMPR) is the standard treatment, dietary interventions may provide additional benefits. The French maritime pine bark extract Pycnogenol® has anti-inflammatory and antioxidant properties, but its impact on inflammatory biomarkers in saliva and serum has not been studied in a controlled clinical trial. Methods: In this randomized, double-blind, placebo-controlled clinical trial, a total of 91 participants received Pycnogenol® (100 mg twice daily; n = 46) or a placebo (n = 45) following PMPR. Saliva and serum samples were collected at baseline, and after two and three months. Biomarkers associated with inflammation (IL-1β, IL-6, MMP-8, MMP-9) and polyphenol concentrations were analyzed using enzyme-linked immunosorbent assays (ELISA) and liquid chromatography-tandem mass spectrometry (LCMS/MS). Results: Pycnogenol® supplementation resulted in a significant reduction in salivary MMP8 levels (p = 0.0261), and lower serum IL-6 levels compared to placebo after three months (p = 0.0409). Additionally, ferulic acid, caffeic acid, and the gut microbial metabolite 5-(3,4-dihydroxyphenyl)-γ-valerolactone (M1) significantly increased in saliva following Pycnogenol® intake. Correlation analysis revealed a significant inverse association between the percentage of bleeding on probing and M1 concentration in saliva (r = -0.3476, p = 0.0167). Conclusion: Dietary supplementation with Pycnogenol® significantly reduced key inflammatory biomarkers and increased polyphenol concentrations in saliva. These findings suggest a potential anti-inflammatory effect of Pycnogenol® on gingival inflammation.

Abstract: Intermediate and advanced-stage hepatocellular carcinoma (HCC) continues to present significant therapeutic challenges. Hepatic artery infusion chemotherapy (HAIC), a well-established locoregional treatment for unresectable HCC, has recently demonstrated promising clinical outcomes both as monotherapy and in combination with systemic therapies. This comprehensive review examines recent clinical advances in HAIC for HCC, with particular emphasis on evolving treatment regimens and their therapeutic efficacy.

Abstract: Background: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. Objectives: To assess whether the previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and March 2025. Patients were divided into the xylazine era (Sept 2022–July 2024) and medetomidine era (Aug 2024–Mar 2025). The primary outcome was change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission. Results: Among 1269 encounters, 616 occurred during the xylazine era and 653 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs −5.0 points, p < 0.0001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs 14.2%, p < 0.0001). ICU admission occurred in 10.6% of xylazine-era patients and 25.7% of medetomidine-era patients. AMA discharge rates were higher during the medetomidine era (8.0% vs 5.9%). Conclusions: The protocol was significantly less effective during the medetomidine era. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply.

Abstract: Streptococcus pneumoniae remains a leading cause of bacterial pneumonia and meningitis in children globally, despite pneumococcal conjugate vaccine (PCV) implementation. We report a case of fatal pneumococcal meningitis in a fully vaccinated 2-year-old male. Despite prior PCV13 vaccination, the patient developed meningitis caused by S. pneumoniae serotype 15B in the cerebrospinal fluid and 15C in the blood. Genomic sequencing revealed nearly identical isolates differing by a capsular switch mutation. This case highlights the limitations of PCV13 against emerging serotypes like 15B and 15C. The recent approval of PCV20, which includes serotype 15B, represents a significant advancement. We propose a PCV20 booster dose for children under five previously vaccinated with PCV13 to enhance protection against the evolving landscape of pneumococcal serotypes and reduce invasive disease. Continued surveillance and adaptive vaccination strategies are crucial, as S. pneumoniae continues to pose a significant threat to young children worldwide.

Abstract: Originally identified as a potential receptor for opioids, sigma-1 receptor is a class of intracellular receptors expressed in various tissues including neurons. As a resident protein in the mitochondria-associated endoplasmic reticulum (ER) membrane, sigma-1 receptor has been found involved in various biological and disease processes including stress responses, neurotransmission, and neurodegenerative diseases. Herein we discuss the history, structure, functions, and pharmacology of sigma-1 receptor and its pathological implications in neurodegenerative diseases.

Abstract: Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PS) of-fers promising cancer treatment potential but requires rigorous safety evaluation. Conju-gated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphy-rin-doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photo-dynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and char-acterized for colloidal stability in parenteral solutions. Hemolysis assays assessed blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 hours for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated ad-ministrations revealed no significant changes in body/organ weights, hematological pa-rameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclu-sions: Platinum porphyrin-doped F8BT CPNs exhibited minimal acute and subacute tox-icity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology.

Abstract: Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Candidate CCMs included genes involved in several immune response pathways, such as POU2F2, which encodes a transcription factor that regulates B-cell maturation. Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays.

Abstract: Background/Objectives: Water and alcohol extracts of Epilobium have gained attention due to the high concentration of its bioactive compounds and associated health benefits. This review aimed to evaluate the effects of Epilobium parviflorum Shreb. (Onagraceae) preparations on vasculature in the light of its medical application on human health over the last five years. Materials and Methods: A literature search of databases such as PubMed/Medline, Scopus, and Google Scholar for original articles published between March 2000 and March 2025 was undertaken. The keywords used were: “aortic rings”, “ellagitannins”, “Epilobium”, “hypotension”, “oenothein B”, “Onagraceae”, “systolic blood pressure”, “vasorelaxation”, “willow herb”. Only one study was found, and this was discussed in this review. Results: Herb of E. parviflorum Shreb. is used as a remedy in folk medicine with a variety of therapeutic properties, including its preventive effects and ability to relieve symptoms in patients with benign prostate hyperplasia, prostatitis, and cancer. Other properties include kidney and urinary tract diseases, skin infections and antibacterial properties. E. parviflorum contains bioactive compounds such as oenothein B, quercetin-3-O-glucuronide and myricetin-3-O-rhamnoside. In a low dose they contribute to the reduction of oxidative stress due to their antioxidant and immunostimulant effects, positively reducing inflammation that causes certain conditions. At higher concentrations Epilobium generates reactive oxygen species that stimulate the body’s defense mechanisms against a variety of cancers. Conclusions: Although the potential application of E. parviflorum in metabolic disorders was not extensively studied before, its antioxidant and anti-inflammatory properties are well documented, which suggests potential pathways for future research and therapeutic development of preparations to benefit vascular health.

Abstract: Abstract: With around 40 species spread throughout temperate and subtropical environments, mostly in East Asia and North America, the genus Lespedeza (L.) (Fabaceae) include Particularly in antioxidant, anti-inflammatory, anticancer, and antidiabetic uses, L. species show notable pharmacological promise due in great part to their high polyphenolic content. The polyphenolic profiles and bioactivities of L. capitata, L. cuneata, and L. bicolor are investigated in this work with an eye on extraction efficiency, total polyphenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity. Corresponding with its higher DPPH radical scavenging IC50 (35.4 µg/mL) and ferric reducing antioxidant power (FRAP) of 912.3 µmol Fe²⁺/g, L. bicolor showed the greatest TPC (190.4 mg GAE/g) and TFC (109.2 mg QE/g). While L. bicolor exhibited strong neuroprotective and anticancer activity, L. cuneata showed strong α-glucosidase inhibition (IC50 = 28.1 µg/mL). L. capitata is nevertheless a great source of bioactive molecules even with its modest bioactivity. The results highlight the possibilities of L. species in nutraceutical and medicinal uses, therefore justifying further study on their bioavailability and molecular processes.

Abstract: Introduction: The treatment of MBC patients is guided by receptor status, with re-biopsy at relapse recommended to reassess hormone receptor (HR) status. Various treatment options are available for HER2- MBC, including CDK4/6 inhibitors, PARP inhibitors, and checkpoint inhibitors. The study highlights the importance of determining receptor subtype for guiding treatment choices. Patients and Methods: The GIM 13 AMBRA study is a longitudinal cohort study involving 42 centers in Italy. It includes data from 939 HER2- MBC patients enrolled between May 2015 and September 2020. The study analyzes the impact of HR expression changes on clinical outcomes using Kaplan-Meier survival curves and other statistical methods. Results: Among the 939 patients, 588 were re-biopsied at first relapse. The study found no significant differences in disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS) between patients whose tumors changed molecular subtype and those who did not. However, post-progression survival from first-line treatment (PPS1) was different between the two groups. Discussion: The study confirms the phenomenon of receptor discordance between primary tumors and metastases. It emphasizes the need for re-biopsy in recurrent MBC to guide treatment strategies. The findings align with previous studies and highlight the importance of understanding receptor changes for improving patient outcomes. Conclusion: The GIM 13 AMBRA study provides valuable insights into the impact of molecular subtype changes on survival outcomes in Luminal MBC patients. It underscores the importance of re-biopsy and personalized treatment strategies in managing metastatic breast cancer.

Abstract: Psilocybin, a psychedelic compound in certain mushrooms, has been used for centuries in spiritual ceremonies and neuropsychiatric therapy. Despite its stigmatization as a Schedule I substance in 1970, research into psilocybin has resurged since the early 2000s, particularly in psychiatry and palliative care. This review examines psilocybin's potential to improve the quality of life in palliative care by reducing psychological distress and enhancing emotional well-being. The discussion includes its historical context, pharmacokinetics, pharmacodynamics, legal status, and future perspectives in palliative care.

Abstract: Background: Forearm fractures are common presentations to the emergency department (ED), frequently requiring reduction and immobilization. In the pediatric population, procedural sedation is the gold standard to allow for appropriate analgesia, patient compliance, and ultimate successful reduction. Hematoma block is another means of analgesia prior to reduction. Hematoma block, however, is often associated with less pain control, limiting quality of reduction. Procedural sedation increases length of stay, resource allocation, and can be associated with complications. A possible alternative for analgesia to facilitate reduction of forearm fractures in the ED, are ultrasound-guided nerve blocks. This is especially significant for the pediatric population, as non-surgical treatment is frequently the standard of care. Methods: Illustrative case series of three pediatric patients who underwent supraclavicular nerve block for management of distal forearm fracture at a tertiary hospital. Results: The indication for supraclavicular nerve block was unique in all patients; avoiding procedural sedation to monitor Glasgow Coma Scale, avoidance of numerous doses of opioids for analgesia, and parental preference to avoid risks of complications associated with procedural sedation. Each reduction was successful on the first attempt. There was no surgical intervention or adverse events in our patients. Conclusions: Supraclavicular nerve block provided a successful alternative to procedural sedation for reduction, analgesia, without adverse events. It holds exceptional potential as an alternative to procedural sedation in a variety of clinical scenarios.

Abstract: Background/Objectives: Carvacrol is a naturally occurring phenolic monoterpene that is one of the major constituents of the essential oils of oregano (Origanum vulgare), thyme (Thymus vulgaris) and other herbs. Carvacrol has anti-inflammatory and antinociceptive effects. At the systemic level, carvacrol is able to activate and inhibit several second messengers and ion channels. However, there is no evidence on the peripheral antinociception of carvacrol and its probable mechanism of action. The aim of this study was to investigate whether the local antinociception of carvacrol involves the opioid receptor-nitric oxide (NO)-GMP-K+ channel pathway. Methods: Formalin (1%) was injected into the dorsal surface of the right hind paw of Wistar rats. Rats received a subcutaneous injection into the dorsal surface of the paw of vehicle or carvacrol (100-300 µg/paw). To determine whether the local antinociception induced by carvacrol was mediated by the opioid receptor-NO-cGMP-K+ channel pathway and a biguanide-dependent mechanism, the effect of pretreatment (10 min before formalin injection) with the corresponding vehicles, naltrexone, L-NAME, 1 H-(1,2,4)-oxadiazolo (4,2-a) quinoxalin-1-one (ODQ), K+ channel blockers, and metformin on the antinociceptive effects induced by local carvacrol (300 µg/paw) were evaluated. Results: Carvacrol produced antinociception during both phases of the formalin test. Naltrexone, L-NAME, ODQ, glibenclamide and glipizide (both ATP-sensitive K+ channel blockers), tetraethylammonium and 4-aminopyridine (both voltage-gated K+ channel blockers), apamin and charybdotoxin (both Ca2+-activated K+ channel blockers), and metformin reversed the carvacrol-induced peripheral antinociception. Conclusions: Local peripheral administration of carvacrol was able to produce significant antinociception and activate the opioid receptor-NO-cGMP-K+ channel pathway. In addition, carvacrol activated a metformin-dependent mechanism at the peripheral level.

Abstract: Background: Tuberculosis and COVID-19 co-infection poses significant clinical challenges, with pulmonary TB (PTB) and extrapulmonary TB (extraPTB) potentially influencing disease progression and outcomes differently. This study aims to compare the clinical manifestations, inflammatory markers, and outcomes between PTB and extraPTB patients with SARS-CoV-2 co-infection. Methods: A retrospective, cross-sectional study was conducted on 55 hospitalized adults with TB-COVID-19 co-infection from March 2020 to March 2022. Patients were divided into PTB (n=32) and extraPTB (n=23) groups. Demographic, clinical, laboratory, and imaging data were collected and analyzed using statistical models, including ANCOVA, LASSO regression, and Random Forest classification, to identify key predictors of hospitalization duration and mortality. Results: PTB patients had significantly lower BMI, worse oxygenation status, and greater lung involvement on CT compared to extraPTB patients. CRP was elevated in PTB, while IL-6 levels were higher in extraPTB. Hospitalization duration was primarily influenced by inflammatory and coagulation markers (IL-6, D-dimer, neutrophil count, systemic inflammatory index), while higher BMI was associated with shorter stays. Mortality risk was strongly correlated with oxygenation impairment (worst SpO₂, SpO₂ at diagnosis), inflammatory burden (CRP, LDH), and CT severity score, rather than TB localization. Conclusions: TB localization did not independently affect hospitalization duration or mortality risk. Instead, severe lung involvement, systemic inflammation, and hypoxemia were the strongest predictors of poor outcomes. These findings emphasize the importance of early risk stratification based on respiratory and inflammatory markers to optimize patient management. Further research is needed to clarify the long-term impact of TB-COVID-19 co-infection, particularly in extraPTB cases.

Abstract: Background: Tendons, along with joints, are among the most affected structures in musculoskeletal disorders. This multicenter, single-cohort, retrospective clinical study evaluated the clinical benefits of Polynucleotides (PNs) injections in reducing pain and improving functionality in patients with tendinopathies. Methods: This retrospective study included 68 patients with different tendinopathies, all diagnosed with persistent pain lasting at least six weeks, accompanied by functional impairment and swelling. Three periarticular/peritendinous injections of a PNs-based medical device were administered at T0 (baseline), FU-1 (two weeks post-T0), and FU-2 (four weeks post-T0), with efficacy and safety assessments at FU-1, FU-2, FU-3 (eight weeks post-FU-2), and FU-4 (24 weeks post-FU-2) groups. The primary outcome measure was pain reduction, assessed using a numerical rating scale (NRS). Secondary outcomes were the Clinical Global Impression–Improvement scale (CGI-I), and patient satisfaction using a 5-point Likert scale. Results: Longitudinal analysis showed an average NRS score reduction of -1.76±0.08 at each follow-up, with statistically significant reductions observed between each follow-up and the final one (FU-4). Based on the CGI-I scale, 78% of the clinicians rated the clinical condition of tendinopathies at FU-4 as "very much improved" or "much improved." Additionally, 88% of patients reported being "satisfied" or "very satisfied" with treatment at the final follow-up (FU-4). No adverse events were reported. Conclusions: As demonstrated by the positive outcomes reported in this study, PNs injections may offer a promising therapeutic option for the treatment of tendinopathies. This study may open up new frontiers for the implementation of conservative approaches in patients affected by tendinopathies.

Abstract: During tissue injury or infection, leukocytes are activated to produce proinflammatory mediators, which trigger the immune system to produce anti-inflammatory and analgesic molecules. Our previous studies provide evidence that synthetic microneurotrophins, like BNN27, exert significant analgesic and anti-inflammatory effects during Complete Freund’s Adjuvant (CFA)-induced inflammation and pain. Thus, the aim of the present study was to examine if the effect of BNN27 on inflammatory pain is mediated at least in part by activation of T-lymphocytes. For this purpose, six hr following the injection of CFA, spleens were harvested in PBS, lymphocytes were collected and placed in medium containing concanavalin-A and IL-2 to prompt T-lymphocyte proliferation and differentiation. Cells were then treated with BNN27 at different concentrations and the media and cells were collected for ELISA and PCR assays. The proliferation rate of T-cells was also examined using the MTT assay. Our results showed that BNN27 significantly increased the proliferation of T-lymphocytes. In addition, BNN27 significantly decreased IL-6 and TNF-α protein levels, while it increased the mRNA expression of μ-opioid receptor and opioid peptides PENK and POMC at different time points. Our data demonstrate considerable anti-inflammatory and analgesic effects of BNN27, making it a promising molecule for inflammation and pain management.

Abstract: Objectives: This study aims to investigate the analgesic potential of extracts from 3 Capsicum species, namely Capsicum chinense (CC), Capsicum frutescens (CF), and Capsicum annuum (CA), using a hot plate test in mice. In addition, the study identified the key bioactive compounds in the extracts through a combined analysis of Fourier Transform Infrared Spectroscopy (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and molecular docking studies. Materials and Methods: During the experimental procedures, extracts from the fruit, stem, and leaves of 3 Capsicum species were prepared using methanol, hexane, and distilled water (aquadest) as solvents. The chemical composition of these extracts was profiled and classified through Fourier-transform infrared (FTIR) spectroscopy combined with cluster analysis. Subsequently, the analgesic activity of the samples was assessed in vivo using the hot plate test in mice. Gas chromatography-mass spectrometry (GC-MS) was used to identify the bioactive compounds present in both the most potent and least potent extracts. Molecular docking studies were then conducted to predict the interactions between these compounds and specific analgesic protein targets, namely 5IKQ, 4TLM, and 4EJ4. Results: The results showed that the aquadest fruit extract of CC had the highest analgesic activity, while extracts from CF and CA had minimal effects. GC-MS analysis showed that the extract with minimal effects contained terpenoids, sterols, vitamins, hydrocarbons, and fatty acids. However, CC was rich in alkaloids capsaicin (4.38%) and dihydrocapsaicin, O-acetyl- (2.26%), terpenoids (nerolidyl acetate) (11.32%), phenolics (2-methoxy-phenol) (1.37%), and fatty acid derivatives. Molecular docking studies confirmed that capsaicin and dihydrocapsaicin, O-acetyl- exhibited strong binding affinities with analgesic protein targets 5IKQ (-8.0 kcal/mol), 4TLM (-5.3 and -4.9 kcal/mol), and 4EJ4 (-7.3 and -6.5 kcal/mol) outperforming the reference drug sodium diclofenac (-8.3, -5.9, and -6.6 kcal/mol). Conclusion: This study described the significant analgesic potential of CC extracts, particularly the aquadest fruit extract, as a promising candidate for developing new pain management therapies.