Serotonin Receptors as a Potential Target in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide that has an increasing impact on aging societies. Besides its critical role in the control of various physiological functions and behavior, brain serotonin (5-HT) system is involved in the regulation of migration, proliferation, differentiation, maturation, and programmed death of neurons. At the same time, a growing body of evidence indicates the involvement of 5-HT neurotransmission in the formation of insoluble aggregates of ß-amyloid and tau protein, the main histopathological signs of AD. The review describes the role of various 5-HT receptors and intracellular signaling cascades induced by them in the pathological processes leading to the development of AD, first of all, in protein aggregation. Changes in the functioning of certain types of 5-HT receptors or associated intracellular signaling mediators prevent accumulation of ß-amyloid plaques and tau protein neurofibrillary tangles. Based on the experimental data, it can be suggested that the use of 5-HT receptors as new drug targets will not only improve cognitive performance in AD, but will be also important in treating the causes of AD-related dementia.

Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a]pyrimidin-4-imines as potent 5-HT6 antagonists.

Comprehensive structure activity relationship (SAR) studies were conducted on a focused screening hit, 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine (1, IC50: 4.0 nM), as 5-HT6 selective antagonists. Activity was improved some 2-4 fold when small, electron-donating groups were added to the central core as observed in 19, 20 and 26. Molecular docking of key compounds in a homology model of the human 5-HT6 receptor was used to rationalize our structure-activity relationship (SAR) findings. In pharmacokinetic experiments, compound 1 displayed good brain uptake in rats following intra-peritoneal administration, but limited oral bioavailability.

The 5-HT1F receptor as the target of ditans in migraine - from bench to bedside.

Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans - a group of selective serotonin 5-HT1F receptor agonists - has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.

Serotonin receptors in epilepsy: Novel treatment targets?

Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5-HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each "5-HT subtype" separately and its relation to "epilepsy or seizures." Most research underlines the antiseizure activity of 5-HT1A,1D,2A,2C,3 agonism and 5-HT6 antagonism. Consistently, FA, which has recently been approved for the treatment of seizures in Dravet syndrome, is an agonist of 5-HT1D,2A,2C receptors. Even though each study focused on a distinct seizure/epilepsy type and generalization of different findings could lead to false interpretations, we believe that the available preclinical and clinical studies emphasize the role of serotonergic modulation, especially stimulation, as a promising avenue in epilepsy treatment.

Atypical antipsychotic use and mortality risk in Parkinson disease.

INTRODUCTION: Dopamine receptor blocking atypical antipsychotic (DRB-AAP) use has previously been associated with increased adverse effects and mortality risk among persons with Parkinson disease (PD). Pimavanserin, the only AAP indicated for PD psychosis in the U.S., is a serotonin receptor inverse agonist/antagonist with no known DRB activity. Early observational data have reported inconsistent findings regarding mortality risk associated with pimavanserin. The objective of this study was to estimate all-cause mortality risks of pimavanserin as compared to DRB-AAPs. METHODS: We conducted a retrospective cohort study using a large U.S. commercial insurance database. Cox proportional hazards models were used to compare all-cause mortality risks between propensity score-matched groups of PD patients who were new users of pimavanserin or a DRB-AAP, further dividing DRB-AAPs into preferred (quetiapine, clozapine) and non-preferred (other remaining AAPs). RESULTS: We identified 775, 4,563, and 1,297 individuals on pimavanserin, preferred, and non-preferred DRB-AAPs, respectively. There was no difference in mortality risk for pimavanserin vs. preferred DRB-AAPs [adjusted hazard ratio (aHR) 0.99, 95% CI: 0.81-1.20], or pimavanserin vs. non-preferred DRB-AAPs (aHR 0.98, 95% CI: 0.79-1.22) in intention-to-treat analyses. CONCLUSION: Mortality risk among PD patients using AAPs did not differ by antipsychotic drug categorization based on mechanism of action. Research on the comparative efficacy and morbidity of AAPs, and the mortality associated with psychosis itself is needed to guide clinical decision-making in the PD population.

Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20-30%, and satisfactory treatment is obtained in 40-60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients' function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms. In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. METHODS: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS. RESULTS: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron plus sertraline and 27.5 to 19.3 for placebo plus sertraline group with a slightly greater drop for granisetron plus sertraline group), while the granisetron plus sertraline group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57) = 4.52,p-value = 0.01). Moreover, in comparison with the placebo plus sertraline group, the proportion of the patients showing complete response was considerably higher among the granisetron plus sertraline group (P-value < 0.01). No major adverse effects were observed in any of the groups. CONCLUSION: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.

Evaluation and Management of Pruritus in Primary Biliary Cholangitis.

Chronic pruritus is a classic symptom in patients with primary biliary cholangitis. It affects up to two-thirds of patients in the course of the disease. Efficient therapy consists of topical treatment combined with systemic options such as anion exchangers, rifampicin, bezafibrate, µ-opioid receptor antagonists, selective-serotonin receptor uptake inhibitors, and gabapentinoids. Future therapeutic approaches may contain the selective blockade of the enterohepatic cycle by inhibiting the ileal bile acid transporter, the agonism at κ-opioid receptors, and antagonism of the mas-related G protein-coupled receptor X4. As nondrug treatment, ultraviolet B therapy, albumin dialysis, and biliary drainage are available at specialized centers.

[The efficacy of the second generation triptan migrepam in the treatment of migraine attacks: results of the comparative study]. / Éffektivnost' triptana vtorogo pokoleniia migrepama v kupirovanii pristupov migreni: rezul'taty sravnitel'nogo issledovaniia.

AIM: To evaluate the efficacy and safety of migrepam in the treatment of migraine attacks. MATERIAL AND METHODS: Sixty patients with episodic migraine with and without aura, aged between 18 and 65 years, were included in the randomized prospective, open, comparative study. Patients of group I (n=30) received migrepam (zolmitriptan) in a dose of 2.5 mg, group II (n=30) received sumatriptan, 50 mg. The following parameters were assessed: intensity of headache, photo-, phonophobia, frequency, severity of the associated symptoms, indicators of the degree of impact of the headache on general condition and quality of life, headache-related disability, functional activity, as well as patient satisfaction with the therapy. RESULTS AND CONCLUSION: A comparison of the initial indicators of the groups did not reveal any significant differences between them both in demographic characteristics and main parameters analyzed. As a result of therapy, a similar pattern of influence of the studied drugs on the intensity of pain and accompanying symptoms is shown. The more significant effect of migrepam on the characteristics of daily functioning, which is accompanied by a higher subjective assessment of the effectiveness of the relief of migraine attacks by the patients, is noted.

Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting.

GR38032F is a specific 5-HT3 (serotonin) receptor antagonist with antiemetic activity in animal and early human studies. We performed a dose-ranging phase I study of GR38032F in 43 evaluable patients receiving cisplatin 60 120 mg/m2 for the first time (38 of these patients were chemotherapy-naive). Intravenous GR38032F was administered over a dose range from 0.01 to 0.48 mg/kg given three times at four-hour intervals beginning one half hour before cisplatin, and patients were observed for 24 hours. An additional five patients were treated with 0.18 mg/kg given three times at six-hour intervals. Excellent antiemetic efficacy was noted, with 44% of patients experiencing no vomiting and 26% no nausea. Major protection from vomiting (less than or equal to 2 episodes) and from nausea (less than or equal to 2 hours) was experienced by 81% and 44%, respectively. Mild to moderate headache (40%), lightheadedness (21%), and elevated transaminase (19%) were the most common adverse events reported. One patient experienced an apparent hypersensitivity reaction that responded to conventional medications. No extrapyramidal reactions or akathisia were seen. GR38032F was effective through most of the dose range. However, efficacy decreased at the 0.01 mg/kg level and number and intensity of adverse events increased at the 0.48 mg/kg level. Analysis of those patients receiving high-dose cisplatin (100 to 120 mg/m2) revealed a positive association of GR38032F dose and antiemetic activity (Fisher's exact test, two-sided; P less than .05). The 5-HT3 receptor antagonists may provide antiemetic efficacy similar to high-dose metoclopramide without antidopaminergic toxicity. The maximum recommended dose on this schedule of GR38032F is 0.36 mg/kg.

Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility.

Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.

[Prevention of side reactions--present status and problems--special references].

The toxicity of chemotherapy affects adversely the QOL of patients and limits the dose of chemotherapy that can be administered. In the last decade, several agents have been developed that offer possible reduction from the toxicity of a range of anticancer agents. Clinical trials to evaluate these agents are intrinsically more difficult to perform. Standardized assessment and management of chemotherapy-induced toxicities have been required to control these adverse events. Recently, practice guidelines are systematically developed statements to assist the practitioner and patients decision about appropriate management for specific clinical circumstances. Guidelines may be useful in producing better care and decreasing cost. Further clinical research is warranted to address significant questions about the most effective way to assess and treat these adverse events. However, it is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Dr. Rothenberg stated in his recent special article titled "Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel" (J Clin Oncol 19: 3801-3807, 2001) that "Close clinical monitoring, early recognition of toxicities and toxicity syndromes, aggressive therapeutic interventions, and with holding therapy in the presence of unsolved drug-related toxicities is recommended for patients receiving intensive chemotherapy regimens".

[Palliative therapy in cancer. 5. Side effects by anticancer drugs and their treatments].

Many chemotherapeutic agents have been evaluated during the last 40 years and some have now an established place in the management of malignant disease. However these agents have a level of toxicity well above any other group of drugs. Chemotherapeutic agents do not discriminate between normal and neoplastic tissue. Chemotherapeutic regimens that are toxic to rapidly dividing malignant cells, are liable to be particularly harmful to lymphoid tissues, bone marrow and the epithelium of the gastrointestinal tract. The side effects due to chemotherapy are classified as immediate, early, delayed and late. Immediate side effects are those that may occur within the first 24 hours of treatment. The most common immediate side effect is nausea and vomiting, due to direct central effect on the vomiting center of the brain. Cisplatin and nitrogen mustard are particularly prone to this complication. The antiemetics usually used are metoclopramide, domperidone and steroid. The efficacies of these drugs are not so good for nausea and vomiting due to cisplatin administration, however several blockades against serotonin M-receptor recently developed are quite effective to nausea and vomiting of chemotherapeutic regimens including cisplatin. Early side effects commence within about one month of therapy. The most common is bone marrow toxicity and can occur after therapy with the vast majority of anticancer drugs. The relative importance of leukopenia and thrombocytopenia vary between the drugs and their route of administration. Recently, hematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSP) have been introduced to granulocytopenia developed by cancer chemotherapy. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy and marked efficacy on infection in granulocytopenic patients were observed. In addition to this, autologous bone marrow transplantation after chemotherapy has been described in patients with solid tumors.

Avances y líneas de investigación en el tratamiento y diagnóstico del tabaquismo / Advances research in the treatment and diagnosis of smoking

En el momento actual con el arsenal terapéutico disponible para ayudar a dejar de fumar las tasas de abstinencia se elevan hasta el 50% en el mejor de los casos. Es por ello que estamos en la necesidad de buscar nuevos tratamientos que consigan mejorar las tasas de abstinencia al año, teniendo en cuenta que los fumadores que van quedando son aquellos con una mayor dependencia. Debemos ahondar en el análisis de nuevas posibilidades con la vareniclina. Disponemos de investigación activa en la búsqueda de nuevas dianas terapéuticas como son los agonistas y antagonistas del GABA y del glutamato, receptores de acetilcolina, agonistas serotoninérgicos, inhibidores selectivos de la monoaminooxidasa, y agonistas noradrenérgicos. Por otra parte, el cigarrillo electrónico requiere posicionarse en el momento actual como tratamiento para dejar de fumar, debiendo profundizar en la investigación de las posibilidades de la estimulación intracraneal magnética, el mindfullness y la vacuna antinicotina, además de buscar biomarcadores que consigan unidos una mayor abstinencia

At the present time, the tobacco abstinence rates increase up to 50% with the therapeutic arsenal available, in the best-case scenario. That is why we are in the need for new treatments that achieve higher abstinence rates per year, given that smokers who remain are those with greater dependence. Also, we must give a thorough look into new possibilities for varenicline. There are on-going investigations searching for new therapeutic targets such as agonists and antagonists of GABA and glutamate, acetylcholine receptors, serotonin agonists, selective inhibitors of monoamine oxidase, and noradrenergic agonists. Moreover, the electronic cigarette requires a position at the present time as a treatment for smoking cessation, and other therapeutic approaches like magnetic intracranial stimulation, mindfulness or nicotine vaccine should be explored as well, added to seeking biomarkers in order to obtain higher abstinence with all these combined

Náuseas y vómitos postoperatorios: fisiopatología, factores de riesgo, profilaxis y tratamiento / Postoperative nausea and vomiting: physiopathology, risk factors, prophylaxis and treatment

Reconocer la importancia de prevenir y tratar precozmente las náuseas y los vómitos postoperatorios (NVPO) es fundamental para evitar complicaciones postoperatorias, mejorar la satisfacción del paciente y permitir el desarrollo de la cirugía mayor ambulatoria y de la cirugía fast-track. El tema de las NVPO podría parecer estancado, pero seguimos avanzando. Aparecen nuevos conceptos y problemas como las náuseas y vómitos postalta, nuevos factores de riesgo y nuevos fármacos. Por otro lado, siguen existiendo ideas erróneas, como asociar las NVPO con la estancia en la unidad de recuperación postanestésica o asumir como factores de riesgo características del paciente, de la anestesia o de la cirugía que realmente no lo son. Debemos enfrentarnos a las NVPO de otro modo, implementando el uso de las guías clínicas en nuestros centros y apostando por una profilaxis más agresiva en determinados grupos de pacientes. Presentamos a continuación una amplia revisión del tema (AU)

Recognising the importance of the prevention and early treatment of postoperative nausea and vomiting (PONV) is essential to avoid postoperative complications, improve patient satisfaction and enable the development of major outpatient surgery and fast-track surgery. The topic of PONV might seem to have become stagnant, but we are moving forward. New concepts and problems like post-discharge nausea and vomiting, new risk factors and new drugs are appearing. However, there continue to be mistaken notions about PONV, such as the association between PONV and post-anaesthesia care unit stays, or assuming that it is a risk factore characteristic of the patient, anaesthesia or surgery when it is not. Perhaps, now is the moment to tackle PONV in a different manner, implementing guidelines and going for more aggressive prophylaxis in some groups of patients. We present an extensive review of this topic (AU)

Efecto de la restricción física: sobre el papel de los receptores 5-HT1A en la proliferación linfocitaria / Effect of phisical restraints: the role of the 5-HT1A in lymphocyte proliferation

El estrés afecta el sistema inmunológico, sin embargo, no hay reportes sobre receptores de serotonina en linfocitos. Se estudiaron los receptores 5-HT1A y la proliferación linfocitaria de ratas macho adultas luego de restricción física. Fueron colocadas en cajas de Plexiglass durante 5 horas diarias por 1, 3 ó 5 días. Se extrajo sangre cardíaca, se aislaron los linfocitos por gradiente de densidades y adhesión al plástico; se cultivaron con el agonista 8-hidroxi-di-n-propil-aminotetralina(8-OH-DPAT) ó el antagonista N-(2-(4-(2-metoxifenil)-1-piperazinetil)-N-(2-piridinil) ciclohexanocarboxamida (WAY-100635) de los receptores 5-HT1A y del mitógeno concanavalina A. La proliferación se midió con sales de tetrazolio. La 8-OH-DPAT no afectó la proliferación. El WAY-100635 disminuyó la proliferación. La restricción física aumentó la sensibilidad al efecto del WAY-100635, lo cual podría deberse a cambios en la expresión o a una modulación funcional de los receptores por efecto del estrés, como se ha reportado previamente en cerebro de rata.

Stress affects the immune system, however, little is known about the effects on specific modifications of lymphocytes serotonin receptors. The effects of restraint stress on the role of 5-HT1A receptors in lymphocyte proliferation were evaluated in male adult rats. They were placed in Plexiglass boxes, during 5 daily hours for 1, 3 or 5 consecutive days. Next day a blood sample was obtained by cardiac punction. Lymphocytes were isolated by density gradient and adhesionto plastic. They were cultured with agonist 8-hydroxy-di-n-propyl-aminotetralin (8-OH-DPAT) or antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2-pyridiyl) cyclohexanecarboxamide (WAY-100635) of 5-HT1A receptors and the mitogen concanavalin A. Proliferation was measured by tetrazolium salts. 8-OH-DPAT did not modify cell proliferation; WAY-100635 diminished it. Restraint stress increased the susceptibility to effect of WAY-100635. These results suggest changes in the expression or functional modulation of 5-HT1A receptors in lymphocytes by stress, similar to previous reports on serotonergic system in rat brain.

The influence of the 5-HT3 receptor antagonist tropisetron on pain in fibromyalgia: a functional magnetic resonance imaging pilot study.

OBJECTIVE: Central pain processing is altered in patients with fibromyalgia syndrome (FMS). The serotonin metabolism, especially the 5-HT3 receptor, seems to play an important role. METHODS: We investigated the effect of the local injection of the 5-HT3 receptor antagonist tropisetron on the perception and central processing of pain in FMS patients using painful mechanical stimulation and functional magnetic resonance imaging (fMRI) within the framework of a pre-/posttreatment double-blind design. RESULTS: In the contralateral primary somatosensory cortex, contralateral posterior insula, and anterior cingulate cortex, we found that the activation was significantly reduced after treatment. On average, patients rated the stimulation-induced pain intensity as stronger in the session after treatment compared to before treatment, although the individual data revealed a heterogeneous pattern. All patients showed sensitisation during the painful stimulation, which was not influenced by the treatment. CONCLUSIONS: Both the sensory-discriminative and motivational-affective components of pain as measured by fMRI were altered by tropisetron.

Tender points as predictors of distress and the pharmacologic management of fibromyalgia syndrome.

The object of this study was to determine the association between tender point pain ratings, tender point counts and distress in people with fibromyalgia and to review the pharmacotherapy of fibromyalgia. Demographic, psychosocial, and health status information was collected from 316 health maintenance organization members with fibromyalgia. A manual tender point exam was conducted. Tender point counts predicted 3.0%, and tender point severity ratings predicted 8.3%, of the variance in distress. Little difference was found between the variance predicted for physical versus psychologic distress. A principal components analysis of all measures produced four distinct factors: global-physical functioning, tender points, psychologic, and physical. Tender point pain ratings and counts predicted a small but significant amount of variance in distress. In addition, FMS involves at least four rather distinct factors, one of which is related to tender points. Pharmacotherapeutic management is provided on a patient-specific basis including pharmacokinetics, pharmacodynamic, pathophysiologic, and psychosocial needs designed and modulated for each individual patient.

Evaluación del dolor lumbo-pélvico tras la aplicación de la manipulación global de la pelvis en pacientes con dismenorrea primaria: estudio piloto / Assessment of low back and pelvic pain after applying the pelvis global manipulation technique in patients with primary dysmenorrhea: a pilot study

Introducción: La dismenorrea primaria (DP) es un desorden ginecológico común en mujeres en edad reproductiva. Se define como el conjunto de síntomas que preceden a la menstruación, siendo el más característico de ellos el dolor en la zona baja del abdomen seguido del dolor lumbo-pélvico. Objetivos: Valorar el efecto de la manipulación global de la pelvis (MGP) sobre el dolor lumbar en pacientes con DP a través de: (i) el dolor lumbo-pélvico percibido; (ii) el umbral del dolor a la presión (UDP) en las articulaciones sacroilíacas (ASIS); (iii) la respuesta endógena del cuerpo frente al dolor con la liberación de catecolaminas y serotonina. Material y Métodos: Estudio experimental, controlado, aleatorizado, doble ciego. Han participado 20 pacientes con DP, 10 formaron parte del Grupo Experimental (GE) y 10 del Grupo Control (GC). Se midió el dolor lumbo-pélvico con una escala visual analógica (EVA), el UDP con un dinamómetro digital y los niveles de catecolaminas/serotonina con una analítica sanguínea. Resultados: El GE obtuvo una mejoría significativa en el UDP de ambas ASIS (p=0.001), no así en el dolor lumbo-pélvico percibido (p=0.129). Asimismo, aumentaron los niveles de serotonina y dopamina en el GE aunque no de manera significativa (p=0.447) y (p=0.255) respectivamente, mientras que disminuyó la concentración en plasma de adrenalina (p=0.819) y noradrenalina (p=0.218). Conclusiones: La MGP mejora el UDP en ambas ASIS en pacientes con DP, no así el dolor lumbo-pélvico medido con EVA. La MGP también aumenta los niveles de serotonina, aunque no de manera significativa, mientras que no produce ningún cambio en los niveles plasmáticos de catecolaminas (AU)

Introduction: Primary Dysmenorrhea (PD) is a common gynaecological disorder in women of childbearing age. The most common premenstrual symptom is pain in the lower abdomen, followed by low back and pelvic pain. Objectives: We aim to assess the effect of global pelvic manipulation (GPM) on low back pain in subjects with PD through the evaluation of the: (i) self-perceived low back-pelvic pain; (ii) pressure pain threshold (PPT) in right and left sacroiliac joints (SIJ), and (iii) endogenous response of the organism to pain following catecholamines and serotonin release. Material and Methods: A randomized, double-blind, controlled clinical trial was performed to evaluated the efficacy of the GPM in the treatment of women with PD. Twenty patients (n=20) with PD were screened, ten (n=10) belonged to the control group (CG) and ten (n=10) to the experimental group (EG). The low back-pelvic pain was measured using Visual Analogue Scale (VAS) scores, the PPT was determined with a digital algometer, and a blood test was performed to determine catecholamines (adrenaline, noradrenalin, and dopamine) and serotonin levels. Results: A significant improvement of the PPT of both SIJ (p = 0.001) was observed in the EG, although there were no differences in the self-perceived low back-pelvic pain (p = 0.129). There was a nonstatistically significant increase in serotonin (p=0.447) and dopamine (p = 0.255) levels, as well as a nonsignificantly decrease in plasma levels of adrenaline (p = 0.819) and noradrenalin (p=0.218) in the EG. Conclusions: The bilateral GPM technique improves the PPT in both SIJ in patients with PD, but it does not affect the self-perceived low back-pelvic pain. The GPM also increases serotonin levels, but not significantly, although no changes are detected in the catecholamines plasma levels(AU)