Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review.

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers' presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Dexketoprofen más pamabrom versus acetaminofen en dismenorrea primaria: estudio controlado, randomizado, doble ciego, multicéntrico / Dexketoprofen plus pamabrom versus acetaminophen in primary dysmenorrhea: a controlled, randomized, double-blind, multicenter study

RESUMEN Introducción: se sabe que las concentraciones plasmáticas de hormona antidiurética o vasopresina son más altas en las mujeres con dismenorrea primaria (DiPr) y podría ser causa de retención de agua con signos y síntomas concomitantes que agravan su cuadro clínico. La monoterapia con AINEs en ocasiones alcanza solo un alivio parcial porque no incide sobre la vasopresina. Objetivo: evaluar la eficacia y tolerabilidad del dexketoprofeno + pamabrom en la DiPr tomando como referencia el acetaminofén. Materiales y métodos: estudio doble ciego, controlado, randomizado, en pacientes con DiPr asignados al azar. Fueron aleatorizadas 172 pacientes, 86 en cada grupo 1) Grupo casos (DP): dexketoprofeno + pamabrom o 2) Grupo control (AC): acetaminofén. Se evaluó la evolución de la intensidad del dolor, el alivio del dolor, la gravedad de otros síntomas presentes y la satisfacción global del médico y paciente. Se registró las reacciones adversas. Resultados: la disminución de la intensidad del dolor, de los síntomas acompañantes y el alivio del dolor evaluados por la EVA, la PID, la SPID, el PAR y el TOTPAR respectivamente es mayor y más rápida de modo significativo en todos los tiempos para la combinación DP. Las reacciones adversas fueron mínimas. La satisfacción global de pacientes y médicos respecto al tratamiento es significativa a favor de la combinación DP. Conclusiones: dexketoprofeno + pamabrom es significativamente más eficaz y rápido en el control del dolor y otros síntomas presentes en la dismenorrea primaria que acetaminofén demostrando la validez de añadir un diurético suave a un AINE para incrementar su eficacia. El tratamiento DP es bien tolerado (AU).

ABSTRACT Background: It is known that plasma concentrations of antidiuretic hormone or vasopressin are higher in women with primary dysmenorrhea (DiPr) and could cause water retention with concomitant signs and symptoms that aggravate the illness. Monotherapy with NSAIDs sometimes achieves only partial relief because it does not affect vasopressin. Objective: The aim was to evaluate the efficacy and tolerability of dexketoprofen + pamabrom in DiPr taking as reference acetaminophen. Materials and methods: Double-blind, controlled, randomized study in patients with DiPr random to 1) Case group (PD): dexketoprofen + pamabrom or 2) Control group (CA): acetaminophen. The evolution of pain intensity, pain relief, severity of other present symptoms and overall satisfaction of the doctor and patient were evaluated. Adverse reactions were recorded. Results: 172 patients were randomized, 86 in each group. The decrease in pain intensity, accompanying symptoms and pain relief evaluated by VAS, PID, SPID, PAR and TOTPAR respectively is significantly greater and faster at all times for the combination DP. Adverse reactions were minimal. The overall satisfaction of patients and doctors regarding treatment is significant in favor of the DP combination. Conclusions: Dexketoprofen + pamabrom is significantly more effective and faster in the control of pain and other symptoms present in primary dysmenorrhea than acetaminophen demonstrating the validity of adding a mild diuretic to an NSAID to increase its effectiveness. DP treatment is well tolerated (AU).

Estudio de niveles séricos de cobre y zinc y su posible rol como indicadores de dismenorrea primaria / Study of serum levels of copper and zinc and its possible roll like indicators of primary dysmenorrheal

En este trabajo se ha determinado el contenido de cobre y zinc en suero sanguíneo de 39 mujeres con edades comprendidas entre 17 y 21 años de edad, n = 25 con dismenorrea primaria diagnosticada clínicamente y n = 14 grupo control con diagnóstico negativo para la patología estudia-da. Las muestras de suero sanguíneo se obtuvieron antes (a) y durante (d) la menstruación. Fueron analizadas por Espectroscopia de Absorción Atómica con inyección en flujo continuo (EAA-IFC). Las concentraciones obtenidas fueron de 1,56 ± 0,43 mgL-1 de cobre y 1,28 ± 0,34 mgL-1 de zinc antes de la menstruación y 1,06 ± 0,23 mgL-1 de co bre y 1,21 ±0,4 mgL-1 de zinc durante la menstruación, para el grupo control y 1,64 ± 0,52 mgL-1 de cobre y 1,88 ± 0,61 mgL-1 de zinc antes de la menstruación y 1,21 ± 0,34 mgL-1 de cobre y 0,94 ± 0,27 mgL-1 de zinc durante la mens ruaciónt en el grupo estudio. Los elementos determinados en ambos grupos antes del periodo menstrual, no observaron diferencias significativas con p= 0,63 y 0,16 para cobre y zinc, respectivamente. Sin embargo, durante la menstruación, fue evidente una diferencia con p < 0,005. Este resultado nos hace presumir, que el aumento brusco de los niveles séricos de cobre se deba probablemente por la alteración de las prostaglandinas, siendo este bioelemento uno de los responsables de las molestias que se presentan en esta patología y otros efectos secundarios motivados por el descenso brusco del zinc. La relación cobre/zinc se calculo en ambos grupos, con valores de 1,47 y 1,06 antes y durante, respectivamente para el grupo control y para el grupo bajo estudio 1,36 y 1,97 antes y durante, respectivamente.

In this work has determined the copper content and zinc in sanguineous serum of women with primary dysmenorrheal diagnosed clinically and a group of women control with I diagnose negative for the studied pathology. The samples of sanguineous serum taken before (a) and during (d) the second day of the menstruation come from 39 women in ages between 17 and 21 years of age, n = 14 controls and n = 25 women with primary dysmenorrheal. They were processed by Spectroscopy of Atomic Absorption with injection in con-tinuous flow (EAA-IFC). The concentrations obtained of 1.56± 0.43 mgL-1 of copper and 1.28± 0.34 mgL-1 of zinc before menstruation and 1.06 ±0.23 mgL-1 of copper and 1.21 ±0.4 mgL-1 of zinc during the menstruation (second day), for the group control and 1.64 ±0.52 mgL-1 of copper and 1.88 ±0.61 mgL-1 of zinc before menstruation and 1.21± 0.34 mgL-1 of copper and 0.94± 0.27 mgL-1 of zinc during the menstruation in the group study. In relation to the serum levels it initiates to them in both groups were not significant differences (p = 0.63). The zinc, observe he himself behavior, between both groups before the menstruation was not observed significant differences with p = 0.16, nevertheless, during the menstruation I throw p = 0.0033. This result evi-dence that indeed the copper is affected by the alteration of the prostaglandins, being probably one of the people in charge of the annoyances that appear in this pa hologyt and other indirect effect motivated by the abrupt reduction of the zinc, such as alteration in the synthesis and excretion of the hormone stimulating follicle (FSH), of the luteinizante hormone (LH), abnormal development of the ovary, alterations of the menstrual cycle. The copper/zinc re ationl I calculate both groups, with values of 1.47 and 1,06 before and during res pectively for the group control and the group under study 1,36 and 1.97 before and during respectively.