ABSTRACT
3,4-Methylenedioxypyrovalerone (MDPV) acts as a dopamine transporter blocker and exerts powerful psychostimulant effects. In this study we aimed to investigate the bidirectional cross-sensitization between MDPV and cocaine, as well as to evaluate the role of the BDNF-TrkB signaling pathway in the development of locomotor sensitization to both drugs. Mice were treated with MDPV (1.5â¯mg/kg) or cocaine (10 or 15â¯mg/kg) once daily for 5â¯days. After withdrawal (10â¯days), animals were challenged with cocaine (8â¯mg/kg) or MDPV (1â¯mg/kg). For biochemical determinations, MDPV (1.5â¯mg/kg) or cocaine (15â¯mg/kg) were administered acutely or repeatedly, and BDNF, D3R and G9a transcription levels as well as pro- and mature BDNF protein levels were determined. Our results demonstrate that repeated administration of MDPV or cocaine sensitizes to cocaine and MDPV locomotor effects. After an acute or a repeated exposure to MDPV, cortical mRNA BDNF levels were increased, while a decrease in mBDNF protein levels in the nucleus accumbens 2â¯h after repeated exposure was evidenced. Interestingly, such decline was involved in the development of locomotor sensitization, thus the pretreatment with 7,8-dihydroxyflavone (10â¯mg/kg), a TrkB agonist, blocked the development of sensitization to MDPV but not to cocaine, for which no changes in the BDNF-TrkB signaling pathway were observed at early withdrawal. In conclusion, a bidirectional cross-sensitization between MDPV and cocaine was evidenced. Our findings suggest that decreased BDNF-TrkB signaling has an important role in the behavioral sensitization to MDPV, pointing TrkB modulation as a target to prevent MDPV sensitization.
Subject(s)
Benzodioxoles/pharmacology , Brain-Derived Neurotrophic Factor/physiology , Cocaine/pharmacology , Flavones/pharmacology , Membrane Glycoproteins/physiology , Motor Activity/drug effects , Protein-Tyrosine Kinases/physiology , Pyrrolidines/pharmacology , Animals , Dopamine Uptake Inhibitors/pharmacology , Dose-Response Relationship, Drug , Male , Mice , Motor Activity/physiology , Signal Transduction/drug effects , Signal Transduction/physiology , Synthetic CathinoneABSTRACT
Antecedentes y objetivos: El dolor crónico oncológico es una experiencia compleja que resulta de la interacción de múltiples factores. Identificar qué factores juegan un papel importante en la configuración de esta experiencia permitiría reducir sus efectos. El objetivo fundamental de este trabajo era identificar qué factores están relacionados con la cronificación del dolor oncológico, a juicio de un grupo de expertos. Y de forma secundaria, se trataba de explorar qué factores podrían actuar de protectores. Material y método: Se invitó a un grupo multidisciplinar de expertos en oncología. Se utilizó la metodología Delphi como forma de llegar al consenso entre los expertos participantes. Resultados: Dos rondas fueron suficientes para alcanzar el consenso. Un total de 22 expertos participaron en ambas rondas. Los principales factores de riesgo identificados fueron: el proceso oncológico, el dolor mal controlado y los factores psicológicos, particularmente el catastrofismo. Entre los factores protectores destacaron: soporte social, tratamiento precoz del dolor, personalidad optimista y adherencia al tratamiento. Conclusiones: Este estudio contribuye a identificar los principales factores que pueden contribuir a la cronificación del dolor oncológico, también aporta información sobre potenciales protectores. Si se confirman por investigaciones futuras, estos resultados pueden ayudar a desarrollar instrumentos diagnósticos específicos con los que identificar las personas en situación de riesgo, así como a crear programas preventivos
Background and objectives: Chronic cancer pain is a complex experience that results from the interaction of multiple factors. Identifying which factors play an important role in shaping this experience would reduce its effects. The main objective of this study was to identify which factors are related to the chronification of cancer pain, in the opinion of a group of experts. And secondarily, to explore which factors might act as protectors. Material and methods: A multidisciplinary group of experts in oncology from various fields was invited. The Delphi methodology was used as a way to reach consensus among the participating experts. Results: Two rounds were enough to reach consensus. A total of 22 experts participated in both rounds. The main risk factors were the oncological process, a poorly controlled pain, and psychological factors, particularly pain catastrophic thinking. Among the main protective factors there were: social support, early pain treatment, optimism, and adherence to treatment. Conclusions: This study contributes to identifying the main factors that can contribute to the chronification of cancer pain, and also provides information on potential protectors. If confirmed by future research, these results can help develop specific diagnostic tools to help identify people at risk, as well as create preventive programs
Subject(s)
Humans , Cancer Pain/epidemiology , Chronic Pain/epidemiology , Catastrophization/epidemiology , Psychosocial Deprivation , Protective Factors , Risk Factors , Catastrophization/prevention & control , Risk Adjustment/methods , Expert Testimony/statistics & numerical dataABSTRACT
Introducción: El dolor neuropático es el problema más habitual en la neuropatía inducida por quimioterapia (NIQ) y el que más interfiere en la calidad de vida de los pacientes. Su detección precoz resulta fundamental para reducir o eliminar los problemas que de este se derivan. Los objetivos de este estudio eran: 1) determinar la incidencia y las características de NIQ y dolor neuropático en pacientes con mieloma múltiple (MM) tratados con bortezomib, y 2) evaluar el impacto del dolor neuropático en las actividades de la vida diaria (AVD). Método: Todos los pacientes diagnosticados de MM candidatos a tratamiento con bortezomib atendidos en el Hospital Joan XXIII durante 2013, participaron. Los participantes eran entrevistados individualmente e informaban sobre la presencia, las características y el impacto del dolor, así como de los efectos adversos del bortezomib. Resultados: Participaron 22 personas, de las cuales la mitad presentaron NIQ, siendo el grado 2 el predominante. La localización más habitual del dolor neuropático era manos y pies; aparecía de manera espontánea y progresiva empeorando en reposo y durante la noche, con predominio de síntomas positivos. El impacto del dolor se reflejó en todas las AVD. La limitación principal fue la incapacidad para disfrutar de la vida. La neuropatía periférica ocupó el primer lugar en orden de importancia subjetiva para el paciente seguido de la fatiga y el estreñimiento. Conclusiones: Una adecuada evaluación y detección precoz del dolor neuropático es fundamental para minimizar su impacto en la calidad de vida del paciente (AU)
Introduction: The neuropathic pain is the most habitual problem in the neuropathy induced by chemotherapy (NIQ) and the one that more interferes in the quality of life of the patients. His precocious detection turns out to be fundamental to reduce or to eliminate the problems that from this one stem. The aims of this study were: 1) determine the incident and NIQ's characteristics and neuropathic pain in patients with mieloma multiple (MM) treated with bortezomib, and 2) to evaluate the impact of the neuropathic pain in the activities of the daily life (AVD). Method: All the patients diagnosed of MM candidates for treatment with bortezomib attended in the Hospital Joan XXIII during 2013, took part. The participants were interviewed individually and were reporting on the presence, the characteristics and the impact of the pain, as well as of the adverse effects of the bortezomib. Results: There took part 22 persons, of which NIQ presented the half, being the degree 2 the predominant one. The most habitual location of the neuropathic pain was hands and feet; it was appearing in a spontaneous and progressive way deteriorating in rest and during the night, with predominance of positive symptoms. The impact of the pain was reflected in all the AVD. The principal limitation was the disability to enjoy the life. The peripheral neuropathy occupied the first place in order of subjective importance for the patient followed by the fatigue and the constipation. Conclusions: A proper assessment and early detection of neuropathic pain is critical to minimizing its impact on the quality of life of patients (AU)
Subject(s)
Cancer Pain/drug therapy , Cancer Pain/etiology , Multiple Myeloma/complications , Bortezomib/adverse effects , Paraneoplastic Polyneuropathy , Quality of Life , Interviews as Topic/methods , Bortezomib/toxicity , Early DiagnosisABSTRACT
INTRODUCTION: The neuropathic pain is the most habitual problem in the neuropathy induced by chemotherapy (NIQ) and the one that more interferes in the quality of life of the patients. His precocious detection turns out to be fundamental to reduce or to eliminate the problems that from this one stem. The aims of this study were: 1) determine the incident and NIQ's characteristics and neuropathic pain in patients with mieloma multiple (MM) treated with bortezomib, and 2) to evaluate the impact of the neuropathic pain in the activities of the daily life (AVD). METHOD: All the patients diagnosed of MM candidates for treatment with bortezomib attended in the Hospital Joan XXIII during 2013, took part. The participants were interviewed individually and were reporting on the presence, the characteristics and the impact of the pain, as well as of the adverse effects of the bortezomib. RESULTS: There took part 22 persons, of which NIQ presented the half, being the degree 2 the predominant one. The most habitual location of the neuropathic pain was hands and feet; it was appearing in a spontaneous and progressive way deteriorating in rest and during the night, with predominance of positive symptoms. The impact of the pain was reflected in all the AVD. The principal limitation was the disability to enjoy the life. The peripheral neuropathy occupied the first place in order of subjective importance for the patient followed by the fatigue and the constipation. CONCLUSIONS: A proper assessment and early detection of neuropathic pain is critical to minimizing its impact on the quality of life of patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Bortezomib/therapeutic use , Multiple Myeloma/drug therapy , Neuralgia/drug therapy , Activities of Daily Living , Female , Humans , Male , Middle Aged , SpainABSTRACT
OBJECTIVES: To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. BACKGROUND: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. METHODS: One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. RESULTS: The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. CONCLUSIONS: This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Histamine/administration & dosage , Migraine Disorders/drug therapy , Migraine Disorders/prevention & control , Adolescent , Adult , Botulinum Toxins, Type A/adverse effects , Double-Blind Method , Female , Histamine/adverse effects , Histamine Agonists/administration & dosage , Histamine Agonists/adverse effects , Humans , Injections, Intramuscular/methods , Injections, Subcutaneous/methods , Male , Middle Aged , Migraine Disorders/physiopathology , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Treatment Outcome , Young AdultABSTRACT
Paralelamente a los cambios sociales que se desarrollan encada etapa de la vida en el transcurso de la historia, laEnfermería, como profesión dinámica, se ha ido adaptandoa nuevos escenarios y nuevas realidades que traspasan elámbito cotidiano del desempeño de su trabajo.La profesión enfermera, ha ido evolucionando creándoseun espacio, ahora imprescindible, en áreas tan importantescomo la cooperación internacional y ayuda humanitaria.Esta ayuda humanitaria está regulada por las leyes delDerecho Internacional y humanitario, y su contribución sebasa en la prevención, asistencia y posterior reconstrucciónde la zona afectada, pudiéndose tratar de una misiónde paz o armada. Esta contribución ha puesto muchasveces en peligro la propia integridad del cooperante enfermero.Esta evolución además ha evolucionado hacia estándaresde alta cualificación basados en el rigor científico,tiene cada vez mayor protagonismo e implicación en temasde mantenimiento y promoción de la salud, no sólo ensociedades estructuradas, sino también en entornos de riesgo,socialmente vulnerables e inseguros(AU)
Parallel to the social changes taking place in everystage of life in the course of history nursing, and dynamicprofession, has adapted to new scenarios an new realitiesthan transcend the everyday level of job performance. Thenursing profession has evolved, creating a space, nowindispensable in such an important areas as internationalcooperation and humanitarian aid. This humanitarian aidis governed by the laws of international law and humanitarianlaw, and its contribution is based on prevention,assistance and the reconstruction of the affected area,being able to try a mission of peace or armed. The contributionhas often threatened the very integrity of the cooperatingnurse. This development has also evolvedtowards a higher qualification standards based on soundscience, is increasingly greater role and involvement inissues of maintenance and health promotion, not only instructured societies, even in environments of risk, sociallyvulnerable and insecure(AU)
Subject(s)
Humans , Male , Female , History of Nursing , Nursing/organization & administration , Nursing/statistics & numerical data , Legislation, Nursing/ethics , Legislation, Nursing/organization & administration , Legislation, Nursing/standards , Nurse Clinicians/education , Nurse Clinicians/history , Nurses/ethics , Nurses/organization & administration , Nurses/trends , Legislation, Nursing/classification , Legislation, Nursing/history , Legislation, NursingABSTRACT
BACKGROUND: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. OBJECTIVE: To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. METHODS: Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. RESULTS: The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). CONCLUSION: The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.
Subject(s)
Fructose/analogs & derivatives , Histamine Agonists/administration & dosage , Histamine/administration & dosage , Migraine Disorders/prevention & control , Neuroprotective Agents/administration & dosage , Adolescent , Adult , Double-Blind Method , Female , Fructose/administration & dosage , Fructose/adverse effects , Histamine/adverse effects , Histamine Agonists/adverse effects , Humans , Injections, Subcutaneous , Male , Middle Aged , Neuroprotective Agents/adverse effects , TopiramateABSTRACT
Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t- test was used to compare means and the Mann-Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.