RESUMEN
OBJECTIVE: Benign prostatic hyperplasia (BPH) is a common chronic disease affecting the health of the urinary system and the quality of life in older adults. Plasmakinetic resection of the prostate (PKRP) is one of the important surgical procedures for treating BPH; However, older adults may experience anesthesia complications and postoperative pain. This retrospective study aimed to assess the effects of preoperative oral gabapentin on anesthesia outcomes in older adults with BPH undergoing PKRP and to provide detailed clinical evidence for improving the impact of surgical treatment. METHODS: The medical records of 178 older adults with BPH who underwent PKRP in Tianjin Hospital from March 2021 to March 2023 were retrospectively analyzed. After excluding 18 patients who did not meet the inclusion criteria, 160 patients were finally included in the study. According to preoperative use of gabapentin, patients were divided into the observation group (n = 75, received gabapentin) and the control group (n = 85, did not receive gabapentin). The baseline data, visual analog scale (VAS) scores, postoperative Ramsay Sedation Scale (RSS) scores, and incidence of adverse reactions were collected. RESULTS: There were no significant differences observed between the two groups in terms of age, body mass index, prostate volume, surgery duration, International Prostate Symptom Score (IPSS), American Society of Anesthesiologists (ASA) classification, history of hypertension and diabetes mellitus, VAS scores at postoperative 36 hours and 48 hours, and RSS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours (p > 0.05). Compared to the control group, the observation group had significantly lower VAS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours (p < 0.001), and the incidence of adverse reactions was significantly lower within 24 hours after surgery (p < 0.05). CONCLUSIONS: Preoperative administration of gabapentin before PKRP could reduce pain severity and the incidence of adverse reactions and improve anesthetic effects in older adults with BPH, which is conducive to postoperative recovery.
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Gabapentina , Hiperplasia Prostática , Humanos , Masculino , Gabapentina/administración & dosificación , Gabapentina/uso terapéutico , Estudios Retrospectivos , Hiperplasia Prostática/cirugía , Anciano , Administración Oral , Cuidados Preoperatorios , Anestesia/métodos , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & controlAsunto(s)
Gabapentina , Humanos , Gabapentina/efectos adversos , Gabapentina/uso terapéutico , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Ácido gamma-Aminobutírico/efectos adversos , Aminas/efectos adversos , Pregabalina/efectos adversos , Pregabalina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/efectos adversos , Dolor/tratamiento farmacológico , Dolor/inducido químicamenteRESUMEN
OBJECTIVE: To co mpare the e ffica cy of transcutaneous elec trica l ner ve stimulation with commercially ava ilab le analgesics in alleviating symptoms of temporomandibular disorders. Methods: The cross-sectional, interventional study was conducted from March 11, 2020, to August 31, 2023, at the Oral and Maxillofa cial S urger y Department of the Armed Forces Institute o f Den tist r y, Rawalpindi, Pakistan, and comprised patients aged 18-65 years who were experiencing pain or distress in the temporomandibular joint region. The par ticipants were divided into intervention group A and control group B. Group A treatment involved applying electrodes near the temporomandibular joint, with parameters adjusted as per the treatment guidelines. Group B subjects received only analgesics along with basic care recommendations. Pain intensit y was assessed using visual analogue scale, while functional impairment and adverse effects were monitored. Data was analysed using SPSS 24. RESULTS: Of the 130 patients initially assessed, 100(77%) were included; 50(50%) in each group. In group A, there were 33(66.0%) fema les and 17(34.0 %) male s wit h overal l mean age 42.8±10.12 years. In group B, there were 30(60%) females and 20(40%) males with overall mean age 46.98±14.09 years. Pain intensity was significantly lower in group A compared to group B post-inter vention (p=0.009). Group A sub jec ts also showed significant post-intervention improvement in terms of mouth opening compared to group B patients (p<0.05). There was no significant intergroup difference with respect to adverse effects (p>0.05). Conclusion: Transcutaneous electrical nerve stimulation was significantly more effective than commercially available analgesics in alleviating symptoms of temporomandibular disorders.
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Trastornos de la Articulación Temporomandibular , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Trastornos de la Articulación Temporomandibular/terapia , Adulto , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto Joven , Adolescente , Dimensión del Dolor , Pakistán , Analgésicos/uso terapéutico , Anciano , Manejo del Dolor/métodosRESUMEN
Background: Limited availability and side effects of opioids have led to an increased use of non-opioid analgesia in animal disease models. However, by affecting the immune-inflammatory reactions, analgesia may disrupt the resolution of the host inflammation and modulate the survival in septic animals. This study used a clinically relevant sepsis mouse model of peritoneal contamination and infection (PCI) to investigate the antinociceptive and anti-inflammatory properties of two non-opioid analgesics. Methods: Adult C57BL/6J mice were intraperitoneally injected with a human feces suspension and received either no analgesics (Non-A), Meloxicam, or Metamizole orally. The mice were monitored for pain and illness. Mortality was assessed at 7 days post-PCI. A separate group of mice was sacrificed 24 hours after infection. Blood, peritoneal lavage fluid (PLF), liver, and spleen were harvested for pathogen load quantification via qPCR, macrophage phenotyping, neutrophil infiltration/activation, and systemic/tissue cytokine release by flow cytometry. Results: Meloxicam but not Metamizole reduced the mortality of septic mice by 31% on day 7 compared to the Non-A group. Both analgesics effectively alleviated pain but did not affect illness severity, body weight, and temperature. Meloxicam quadrupled the bacterial burden in the blood and PLF. In high IL-6 responders, Meloxicam treatment was associated with reduced circulating IL-10 and IL-1ß compared to the Non-A septic group. In low IL-6 responders, Meloxicam increased circulating MCP-1 levels and decreased PGE2 levels compared to Non-A septic mice. Notably, Meloxicam reduced spleen neutrophil infiltration by 20% compared to two other sepsis groups. Conclusion: Metamizole and Meloxicam effectively relieved pain and increased the animals' basal activity in the PCI sepsis model. Meloxicam prolonged survival yet triggered maladaptive responses due to its immunosuppressive features that decreased tissue bacterial clearance during sepsis. In contrast, Metamizole constitutes a safe and effective non-opioid alternative for analgesic control in the non-surgical PCI sepsis model.
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Dipirona , Modelos Animales de Enfermedad , Meloxicam , Ratones Endogámicos C57BL , Sepsis , Animales , Meloxicam/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Sepsis/mortalidad , Dipirona/uso terapéutico , Dipirona/farmacología , Ratones , Analgésicos/uso terapéutico , Analgésicos/farmacología , Inmunomodulación/efectos de los fármacos , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Masculino , Citocinas/metabolismo , Citocinas/sangre , Peritonitis/tratamiento farmacológico , Peritonitis/inmunología , Peritonitis/microbiología , Peritonitis/mortalidad , HumanosRESUMEN
Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP's efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1ß, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies.
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Analgésicos , Antiinflamatorios , Gynostemma , Osteoartritis , Extractos Vegetales , Animales , Gynostemma/química , Ratones , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Osteoartritis/inducido químicamente , Osteoartritis/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Células RAW 264.7 , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Cartílago Articular/metabolismo , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: This study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors. METHODS: From a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (< 30-day supply) and long-term (≥ 30-day supply) prescription fills] and healthcare resource utilization (healthcare costs, hospitalizations, and emergency department visits) were compared between acupuncture-treated and non-treated patients. RESULTS: Among 495 (3%) acupuncture-treated patients (median age: 55 years, stage 4: 12%, average 2.5 years post cancer diagnosis), most had commercial health insurance (92%) and experiencing musculoskeletal pain (98%). Twenty-seven percent were receiving antidepressants and 3% completed ≥ 2 long-term prescription fills of opioids. Prevalence of opioid usage reduced from 29 to 19% (P < 0.001) and NSAID usage reduced from 21 to 14% (P = 0.001) post-acupuncture. The relative prevalence of opioid and NSAID use decreased by 20% (P < 0.05) and 19% (P = 0.07), respectively, in the acupuncture-treated group compared to non-treated patients (n = 16,129). However, the reductions were not statistically significant after adjustment for confounding. Patients receiving acupuncture for pain (n = 264, 53%) were found with a relative decrease by 47% and 49% (both P < 0.05) in short-term opioid and NSAID fills compared to those treated for other conditions. High-utilization patients (≥ 10 acupuncture sessions, n = 178, 36%) were observed with a significant reduction in total healthcare costs (P < 0.001) unlike low-utilization patients. CONCLUSIONS: Although adjusted results did not show that patients receiving acupuncture had better outcomes than non-treated patients, exploratory analyses revealed that patients treated specifically for pain used fewer analgesics and those with high acupuncture utilization incurred lower healthcare costs. Further studies are required to examine acupuncture effectiveness in real-world settings.
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Terapia por Acupuntura , Analgésicos , Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/terapia , Adulto , Terapia por Acupuntura/economía , Analgésicos/uso terapéutico , Analgésicos/economía , Aceptación de la Atención de Salud/estadística & datos numéricos , Estados Unidos/epidemiología , Adulto Joven , Adolescente , Manejo del Dolor/métodos , Dolor en Cáncer/terapia , Dolor en Cáncer/tratamiento farmacológicoRESUMEN
BACKGROUND: This study aims to investigate the efficacy of five analgesic strategies combined with conventional physiotherapy program (CPT) in managing chronic shoulder pain. METHODS: Two authors independently screened studies, extracted data using a pre-formatted chart, and assessed bias using the Cochrane Risk of Bias tool. A network meta-analysis was performed by the Stata 17.0 and R 4.3.2 software. RESULTS: A total of 14 studies with 862 subjects were identified. These analgesic strategies included extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). ESWT plus CPT was the most efficient intervention in alleviating pain intensity and improving physical function. SSNB plus CPT was the optimal intervention in improving shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility. CONCLUSION: Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Future rigorous clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results.
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Dolor Crónico , Metaanálisis en Red , Modalidades de Fisioterapia , Dolor de Hombro , Humanos , Dolor de Hombro/terapia , Dolor Crónico/terapia , Resultado del Tratamiento , Terapia Combinada , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Bloqueo Nervioso/métodos , Ácido Hialurónico/administración & dosificación , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Masculino , Femenino , Corticoesteroides/administración & dosificación , Analgesia/métodos , Cinta Atlética , Persona de Mediana EdadRESUMEN
BACKGROUND: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. OBJECTIVES: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. METHODS: This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. RESULTS: In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. CONCLUSION: Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate.
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Analgésicos , Ansiolíticos , Antidepresivos , Ansiedad , Depresión , Hogares para Ancianos , Casas de Salud , Dimensión del Dolor , Dolor , Calidad de Vida , Humanos , Masculino , Femenino , Ansiolíticos/uso terapéutico , Anciano , Anciano de 80 o más Años , Antidepresivos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/psicología , Dolor/diagnóstico , Depresión/tratamiento farmacológico , Depresión/psicología , Depresión/diagnóstico , Ansiedad/psicología , Ansiedad/tratamiento farmacológico , Ansiedad/diagnóstico , Analgésicos/uso terapéutico , Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.
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Analgésicos , Neuropatías Diabéticas , Formaldehído , Quercetina , Animales , Ratones , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/inducido químicamente , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Modelos Animales de Enfermedad , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Yohimbina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Naloxona/farmacología , Naloxona/uso terapéutico , Estreptozocina , Dimensión del Dolor/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
Background: Rheumatoid arthritis (RA) is one of the most common forms of arthritis. Extracorporeal shockwave therapy (ESWT) has been identified as a viable alternative therapeutic approach in light of the present protracted clinical course of pharmacological treatment, and changes in levels of marker proteins in the blood samples of RA patients can be utilized to assess treatment outcomes. Methods: A randomized controlled trial was conducted involving forty patients diagnosed with rheumatoid arthritis (RA) who were assigned randomly to two groups. The first group received a combination of diclofenac and methotrexate (MTX) consisting of 25 mg of diclofenac administered thrice daily and 15 mg of MTX administered once weekly. Individual follow-up assessments were carried out after 7 and 14 days. Meanwhile, patients in the second group underwent two sessions of Extracorporeal Shockwave Therapy (ESWT), with a 7-day interval between sessions. Evaluations were conducted on day 7 and day 14. Patients who displayed pain control and stability were advised to continue the treatment, whereas those who had inflammation and discomfort were administered specific medications, and their progress was closely monitored until day 28. Blood samples were collected from both groups prior to treatment, after the first treatment, and after the second treatment. Four marker proteins (NRP-1, CELF-6, COX-2, and RGS-1) and two inflammatory cytokines (IL-6 and IL-17) were measured using western blot and RT-PCR techniques. A statistical analysis was conducted on the levels of specific proteins and inflammatory factors before and after treatment to evaluate its impact. Result: Both groups exhibited statistically significant differences in the serum level of target biomarkers before and after the intervention. However, the ESWT group demonstrated a more noticeable effect, while the diclofenac + MTX group exhibited a delayed anti-inflammatory effect compared to ESWT. Conclusion: Both treatments significantly improved joint function, relieved pain, and reduced inflammation in patients. However, ESWT demonstrated a more prominent clinical analgesic effect compared to the combination treatment of diclofenac and MTX. Furthermore, ESWT produced a more immediate and noteworthy anti-inflammatory impact by regulating NRP-1 expression, a trophic factor receptor that facilitates vascular endothelial cell migration and tissue repair through angiogenesis, and regulating RGS-1 to limit inflammatory signal transmission and immune cell activation.
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Artritis Reumatoide , Biomarcadores , Diclofenaco , Tratamiento con Ondas de Choque Extracorpóreas , Metotrexato , Humanos , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Diclofenaco/uso terapéutico , Diclofenaco/administración & dosificación , Artritis Reumatoide/sangre , Artritis Reumatoide/terapia , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Adulto , Biomarcadores/sangre , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Resultado del Tratamiento , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia Combinada , Analgésicos/uso terapéutico , AncianoRESUMEN
INTRODUCTION: We aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR). METHODS: We performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010-2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88-0.97), SYSADOA (0.87;0.83-0.91) and acetaminophen (0.84;0.79-0.89), and an high risk for metamizole (1.07;1.03-1.12), and antiplatelet drugs (1.07;1.03-1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88-0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03-1.15) and Coxibs (1.19;1.08-1.30). Medium and high use of major opioids shows a high risk (1.15;1.03-1.29). Triflusal showed high risk at medium (1.23;1.02-1.48) and high use (1.68;1.40-2.01). CONCLUSION: We observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.
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Analgésicos , Antiinflamatorios no Esteroideos , Bases de Datos Factuales , Tasa de Filtración Glomerular , Inhibidores de Agregación Plaquetaria , Humanos , Femenino , Masculino , Anciano , Antiinflamatorios no Esteroideos/uso terapéutico , Estudios de Casos y Controles , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Tasa de Filtración Glomerular/efectos de los fármacos , Analgésicos/uso terapéutico , Anciano de 80 o más Años , Persona de Mediana Edad , España/epidemiología , Riñón/efectos de los fármacos , Riñón/fisiopatologíaRESUMEN
Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays a pivotal role in nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, and physical stressors. Dysregulation of TRPV1 signaling further contributes to the pathophysiology of neuropathic pain. Therefore, targeting TRPV1 is a promising strategy for developing novel analgesics with improved efficacy and safety profiles. Several pharmacological approaches to modulate TRPV1 activity, including agonists, antagonists, and biological TRPV1 RNA interference (RNAi, small interfering RNA [siRNA]) have been explored. Despite preclinical success, the clinical translation of TRPV1-targeted therapies has encountered challenges, including hyperthermia, hypothermia, pungency, and desensitization. Nevertheless, ongoing research efforts aim to refine TRPV1-targeted interventions through structural modifications, development of selective modulators, and discovery of natural, peptide-based drug candidates. Herein, we provide guidance for researchers and clinicians involved in the development of new interventions specifically targeting TRPV1 by reviewing the existing literature and highlighting current research activities. This study further discusses potential future research endeavors for enhancing the efficacy, safety, and tolerability of TRPV1 candidates, and thereby facilitates the translation of these discoveries into effective clinical interventions to alleviate neuropathic pain disorders.
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Neuralgia , Canales Catiónicos TRPV , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Humanos , Animales , Analgésicos/farmacología , Analgésicos/uso terapéuticoRESUMEN
Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.
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Analgésicos , Epóxido Hidrolasas , Neuralgia , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Animales , Neuralgia/tratamiento farmacológico , Masculino , Ratones , Analgésicos/farmacología , Analgésicos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Urea/análogos & derivados , Urea/farmacología , Evaluación Preclínica de Medicamentos , Edema/tratamiento farmacológico , Ratas , Adamantano/análogos & derivados , Adamantano/farmacología , Adamantano/uso terapéuticoRESUMEN
OBJECTIVE: Patients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients. METHODS: This retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment. RESULTS: A total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P < 0.05), with no differences between groups (P > 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P < 0.05), but no significant differences were observed at 1 month, 2 months, and 3 months (P > 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P < 0.05), with no statistical differences at 1 month, 2 months, and 3 months post-treatment (P > 0.05). CONCLUSION: Both PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.
Asunto(s)
Analgesia Controlada por el Paciente , Depresión , Ketamina , Neuralgia Posherpética , Humanos , Neuralgia Posherpética/tratamiento farmacológico , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Depresión/tratamiento farmacológico , Depresión/complicaciones , Analgesia Controlada por el Paciente/métodos , Sufentanilo/uso terapéutico , Sufentanilo/administración & dosificación , Analgésicos/uso terapéutico , Analgésicos/administración & dosificación , Administración Intravenosa , Dimensión del DolorRESUMEN
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.
Asunto(s)
Aconitina , Aconitum , Analgésicos , Aconitina/análogos & derivados , Aconitina/farmacología , Aconitina/uso terapéutico , Humanos , Analgésicos/uso terapéutico , Analgésicos/farmacología , Animales , Aconitum/química , Diterpenos/uso terapéutico , Diterpenos/farmacología , Diterpenos/químicaRESUMEN
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.
Asunto(s)
Trastornos Migrañosos , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Analgésicos/uso terapéutico , Sociedades Médicas/normasRESUMEN
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.
Asunto(s)
Analgésicos , Antiinflamatorios , Antineoplásicos , Apoptosis , Supervivencia Celular , Quinoxalinas , Animales , Quinoxalinas/farmacología , Quinoxalinas/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos/farmacología , Ratones , Apoptosis/efectos de los fármacos , Humanos , Supervivencia Celular/efectos de los fármacos , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Masculino , Células HT29 , Ensayo de Inmunoadsorción Enzimática , Peritonitis/tratamiento farmacológicoRESUMEN
Neuropeptides, including tachykinins, CGRP, and somatostatin, are localized in a peptidergic subgroup of nociceptive primary afferent neurons. Tachykinins and CGRP are pronociceptive, somatostatin is an antinociceptive mediator. Intensive drug research has been performed to develop tachykinin and CGRP antagonists, and somatostatin agonists as analgesics. CGRP receptor antagonists are efficacious and well-tolerated drugs in migraine. Monoclonal antibodies against CGRP or its receptor are used for the prophylactic treatment of migraine. Tachykinin NK1 receptor antagonists failed as analgesics but are used for chemotherapy-induced nausea and vomiting. New, orally active somatostatin 4 receptor agonists are promising drug candidates for treating various pain conditions.