RESUMEN
Objective: Relying on anthropomorphism research, Illness Personification Theory (ILL-PERF) posits that individuals living with a chronic illness ascribe human-like characteristics to their illness. Herein we examine the personification of chronic pain using a new measure: the Ben-Gurion University Illness Personification Scale (BGU-IPS). Method: Three samples of chronic pain patients (Sample 1 and 2 are distinct samples sharing similar characteristics, collected in the context of a cross-sectional design, Ns = 259, 263; Sample 3: a 2-waves longitudinal, N =163) completed the 12-item BGU-IPS, and measures of pain and related factors. Results: An orthogonal, two-factor structure was revealed for the BGU-IPS pertaining to negative vs. positive personifications. Negative personification was associated with pain intensity and illness-related distress (e.g., depression and low adjustment to pain). Positive personification was correlated with hope, pain-related sense of control, and low depression. However, positive personification also augmented the associations between negative personification and several risk factors. Conclusions: Pain personification, particularly as assessed via the BGU-IPS, plays a major role in (mal)adaptation to chronic pain.
Asunto(s)
Dolor Crónico , Humanos , Universidades , Estudios TransversalesRESUMEN
OBJECTIVE: We examined the effects of exposure to missile attacks on patients' pain and depressive symptoms, moderated by pain-related catastrophizing. METHOD: One-hundred Israeli chronic pain patients were assessed both prior and subsequent to military operation "Protective Edge," during which thousands of missiles landed on populated areas across the country. Baseline assessment included pain, depression, and catastrophizing, and postwar assessment tapped exposure to missiles, pain, and depression. RESULTS: Media exposure predicted an increase in sensory pain under high levels of catastrophizing (1 SD above the mean; unstandardized simple slope = 0.57, p = .01), and depression in the entire sample (b = 0.61, p = .01). Perceived stress related to the missiles exhibited an expected effect, predicting an increase in depressive symptoms (b = 1.45, p = .03). Unexpectedly, perceived stress predicted a decrease in sensory pain under high levels of catastrophizing (unstandardized simple slope = -0.49, p = .02). CONCLUSIONS: Media exposure to acute stress may render chronic pain patients more vulnerable to experiencing pain and depressive symptoms, depending on their use of pain-based catastrophizing. High catastrophizers may attend more to outside threats, amplifying the sensory and affective aspects of pain they experience. Perceived stress also plays a significant role in eliciting depressive symptoms in this population. (PsycINFO Database Record
Asunto(s)
Catastrofización/psicología , Dolor Crónico/complicaciones , Dolor Crónico/psicología , Medios de Comunicación de Masas , Estrés Psicológico/complicaciones , Exposición a la Guerra , Adulto , Anciano , Catastrofización/complicaciones , Depresión/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Chronic physical pain is one of modern medicine's principal challenges. Recently, there has been a keen research interest in the role of depressive personality vulnerability (DPV) in the course of chronic pain. This is the first attempt to examine the role of three leading DPV dimensions-sociotropy, autonomy, and self-criticism-in chronic pain. METHOD: Chronic pain patients (N = 428) were assessed four times as to their pain, disability, anxious depression, and pain-based catastrophizing. At Time 1, sociotropy, autonomy, and self-criticism were also assessed. The effects of sociotropy, autonomy, and self-criticism on pain, disability, anxious depression, and pain-based catastrophizing were examined using structural equation modeling analyses. RESULTS: All DPV dimensions uniquely predicted Time 1, but not Time 2, anxious depression. Sociotropy predicted Time 1 pain and catastrophizing over and above anxious depression, as well as an increase in catastrophizing over time. Autonomy predicted a decrease in catastrophizing and disability, and Time 1 anxious depression predicted an increase in self-criticism. CONCLUSIONS: Sociotropy appears to be a unique dimension of DPV in chronic pain.
Asunto(s)
Ansiedad/fisiopatología , Catastrofización/fisiopatología , Dolor Crónico/fisiopatología , Depresión/fisiopatología , Relaciones Interpersonales , Autonomía Personal , Personalidad/fisiología , Autoimagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: In chronic pain, patients' coping affects their adaptation. In two studies, we examined the role of pain catastrophizing, a maladaptive coping strategy, in pain, distress, and disability. In Study 2 we compared catastrophizing to pain acceptance and to other coping strategies. METHODS: Study 1. Chronic pain patients (N = 428) were assessed four times as to their pain, disability, catastrophizing, and distress (depression and anxiety). Study 2. Patients (N = 165) were assessed as to coping and pain acceptance, pain, related distress, depression, hope, suicidal ideations, perceived burdensomeness, and thwarted belongingness. RESULTS: Study 1. A Structural Equation Modeling (SEM) analysis revealed that Time 1 Pain-based catastrophizing prospectively predicted pain (ß =.36, p < .001). Distress prospectively predicted pain related disability (ß = .34, p <.001). Study 2. Pain-based catastrophizing predicted sensory pain (ß = .22, p = .018), depression (ß = .43, p < .001), and suicidal ideation (O.R. = 1.88), which were also predicted by depression and perceived burdensomeness. Distraction predicted sensory pain (ß = .21, p = .017, respectively). Activity engagement predicted low levels of depression (ß = -.29, p < .001, respectively), and willingness to accept pain predicted low pain-related distress (ß = -.16, p = .05). CONCLUSIONS: Pain catastro-phizing and pain acceptance constitute risk and resilience factors. Both should be assessed and targeted in pain management.
Asunto(s)
Ansiedad/psicología , Catastrofización/psicología , Dolor Crónico/psicología , Depresión/psicología , Ideación Suicida , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/complicaciones , Catastrofización/complicaciones , Dolor Crónico/complicaciones , Depresión/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings.
Asunto(s)
Dolor Agudo/diagnóstico , Dolor Agudo/fisiopatología , Algoritmos , Frecuencia Cardíaca/fisiología , Adulto , Femenino , Humanos , Masculino , Procesamiento de Señales Asistido por Computador , Análisis de Ondículas , Adulto JovenRESUMEN
OBJECTIVE: The current study sets out to examine the longitudinal relationship between pain, pain-related disability, and symptoms of depression and anxiety. The latter symptoms are highly prevalent in chronic pain and seriously impede functioning and quality of life. Nevertheless, the direction of the relationship involving these variables among individuals with chronic pain is still unclear. METHODS: Four-hundred twenty-eight individuals with chronic pain (238 women, mean age 54.84 years, mean pain duration 85.21 months) treated at two pain clinics completed questionnaires regarding their pain (Short-Form McGill Pain Questionnaire), depression (Center for Epidemiological Studies-Depression Scale), state anxiety (State-Trait Anxiety Inventory), and pain-related disability (Pain Disability Index) at four time points, with an average of 5 months between measurements. Cross-lagged, structural equation modeling analyses were performed, enabling the examination of longitudinal associations between the variables. RESULTS: Significant symptoms of both depression and anxiety were reported by more than half of the sample on all waves. A latent depression/anxiety variable longitudinally predicted pain (ß = .27, p < .001) and pain-related disability (ß = .38, p < .001). However, neither pain (ß = .10, p = .126) nor pain-related disability (ß = -.01, p = .790) predicted depression/anxiety. CONCLUSIONS: Among adult patients with chronic pain treated at specialty pain clinics, high levels of depression and anxiety may worsen pain and pain-related disability.
Asunto(s)
Actividades Cotidianas , Ansiedad/epidemiología , Dolor Crónico/epidemiología , Depresión/epidemiología , Dimensión del Dolor , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Dolor Crónico/psicología , Estudios de Cohortes , Depresión/psicología , Evaluación de la Discapacidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Low back pain (LBP) is a well-known reason people worldwide seek medical help and it is a Leading cause of chronic pain and disability among people of working age. Recent research reveals that the female gender is not only a risk factor for developing LBP but it may also influence the management of this common condition. OBJECTIVES: Our objective was to evaluate gender-related differences in the management of LBP patients in a specialized hospital-based chronic pain unit. METHODS: A cross-sectional survey was carried out through telephone interviews and the hospital computerized database (N = 129). Socio-demographic, Lifestyle, occupational and medical variables were collected, and their association with the frequency of use of five different diagnostic and/or therapeutic modalities was examined using gender stratification. RESULTS: After adjustment for age, religion, socioeconomic data and the number of co-morbid conditions, women were more prone to poly-pharmacy of analgesic medications prescribed in the previous year compared to men (p = 0.024) and exhibited an increased rate of treatment cessations due to adverse effects (p < 0.001). Interestingly, while women tended to utilize more healthcare services besides the pain clinic (p = 0.097), men tended on average to have more visits than women to the pain clinic for their complaints (p = 0.019). Among those who applied for insurance compensation for LBP-related disability, women exhibited increased use of imaging procedures compared to men (p = 0.038). CONCLUSIONS: This cross-sectional study reveals gender-related differences in management and health services utilization for treatment of LBP in the chronic pain clinic. If confirmed in other centers, these findings should inspire gender-sensitive resource management of the treatment of chronic pain patients. Moreover, the findings suggest that increased awareness of gender bias when seeking insurance compensation for LBP-related disability is warranted.
Asunto(s)
Analgésicos/uso terapéutico , Dolor Crónico/terapia , Servicios de Salud/estadística & datos numéricos , Dolor de la Región Lumbar/terapia , Adulto , Analgésicos/administración & dosificación , Analgésicos/efectos adversos , Estudios Transversales , Recolección de Datos , Personas con Discapacidad/estadística & datos numéricos , Femenino , Humanos , Seguro de Salud/estadística & datos numéricos , Israel , Masculino , Persona de Mediana Edad , Clínicas de Dolor/estadística & datos numéricos , Polifarmacia , Factores Sexuales , Sexismo/estadística & datos numéricosRESUMEN
BACKGROUND: Aseptic technique and handwashing have been shown to be important factors in perioperative bacterial transmission, however compliance often remains low despite guidelines and educational programs. Infectious complications of neuraxial (epidural and spinal) anesthesia are severe but fortunately rare. We conducted a survey to assess aseptic technique practices for neuraxial anesthesia in Israel before and after publication of international guidelines (which focused on handwashing, jewelry/watch removal and the wearing of a mask and cap). METHODS: The sampling frame was the general anesthesiology workforce in hospitals selected from each of the four medical faculties in Israel. Data was collected anonymously over one week in each hospital in two periods: April 2006 and September 2009. Most anesthesiologists received the questionnaires at departmental staff meetings and filled them out during these meetings; additionally, a local investigator approached anesthesiologists not present at these staff meetings individually. Primary endpoint questions were: handwashing, removal of wristwatch/jewelry, wearing mask, wearing hat/cap, wearing sterile gown; answering options were: "always", "usually", "rarely" or "never". Primary endpoint for analysis: respondents who both always wash their hands and always wear a mask ("handwash-mask composite") - "always" versus "any other response". We used logistic regression to perform the analysis. Time (2006, 2009) and hospital were included in the analysis as fixed effects. RESULTS: 135/160 (in 2006) and 127/164 (in 2009) anesthesiologists responded to the surveys; response rate 84% and 77% respectively. Respondents constituted 23% of the national anesthesiologist workforce. The main outcome "handwash-mask composite" was significantly increased after guideline publication (33% vs 58%; p = 0.0003). In addition, significant increases were seen for handwashing (37% vs 63%; p = 0.0004), wearing of mask (61% vs 78%; p < 0.0001), hat/cap (53% vs 76%; p = 0.0011) and wearing sterile gown (32% vs 51%; p < 0.0001). An apparent improvement in aseptic technique from 2006 to 2009 is noted across all hospitals and all physician groups. CONCLUSION: Self-reported aseptic technique by Israeli anesthesiologists improved in the survey conducted after the publication of international guidelines. Although the before-after study design cannot prove a cause-effect relationship, it does show an association between the publication of international guidelines and significant improvement in self-reported aseptic technique.
RESUMEN
This study focused on the effects of exposure to terrorist missile attacks on the physical and mental well being of chronic pain patients. In this prospective and longitudinal design, 55 chronic pain patients treated at a specialty pain clinic completed self-report questionnaires regarding their pain, depression and anxiety pre- and post a three week missile attack on the southern region of Israel. In addition, levels of direct and indirect exposure to the attacks were measured. Results of regression analyses showed that exposure to the attacks through the media predicted an increase in pain intensity and in the sensory component of pain during the pre-post war period, but did not predict depression, anxiety or the affective component of pain. These findings contribute to the understanding of the effects of terrorism on physical and emotional distress and identify chronic pain patients as a vulnerable population requiring special attention during terrorism-related stress.
Asunto(s)
Dolor Crónico/psicología , Medios de Comunicación de Masas , Televisión , Terrorismo/psicología , Guerra , Adaptación Psicológica , Adulto , Anciano , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Estudios de Cohortes , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Femenino , Humanos , Israel , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Clínicas de Dolor , Dimensión del Dolor , Factores de Riesgo , Encuestas y Cuestionarios , Poblaciones Vulnerables/psicologíaRESUMEN
OBJECTIVE: To examine the predictive value of physician's prognosis after patient's first visit to a pain specialty clinic. DESIGN: This is a prospective-longitudinal study in which patients completed questionnaires regarding their pain and psychological constructs before their first visit to a pain specialist and again after an average of 5 months. Physicians rated patient's prognosis immediately after the first visit. SETTING: This study was conducted at the outpatient specialty pain clinic at Soroka University Medical Center. PATIENTS: Forty-five chronic pain patients suffering from a range of nonmalignant pain conditions. OUTCOME MEASURES: Sensory and affective pain measured by the Short-Form McGill Pain Questionnaire and depressive symptoms measured by the Center for Epidemiological Studies-Depression Scale. RESULTS: Multiple regression analysis revealed that physician's rating of patient prognosis at Time 1 uniquely predicted subsequent depressive symptoms and affective pain but not sensory pain at Time 2 even after controlling for Time 1 levels of these variables. CONCLUSION: Physician's pessimistic evaluation of patient's prognosis after the first visit was longitudinally associated with an increase in depression and in the affective dimension of pain over time, but not with changes in the sensory component of pain. Referring to physician pessimism as a marker for pre-depressed patient may lead to early preventive interventions.
Asunto(s)
Trastorno Depresivo/psicología , Trastornos del Humor/psicología , Dolor/diagnóstico , Dolor/psicología , Adulto , Anciano , Actitud del Personal de Salud , Enfermedad Crónica , Trastorno Depresivo/etiología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Trastornos del Humor/etiología , Dolor/complicaciones , Dimensión del Dolor , Pacientes Desistentes del Tratamiento , Pronóstico , Estudios Prospectivos , Análisis de Regresión , Encuestas y CuestionariosRESUMEN
In this study, we examined the overlap between pain and depression in a sample of 342 chronic pain patients treated at a specialty pain clinic. Confirmatory factor analysis was conducted to test the differentiation of pain and depression measured as latent factors derived from the subscales of the Short Form McGill Pain Questionnaire and the Center for Epidemiological Studies Depression Scale. The affective pain subscale did not load on latent depression and the somatic depression subscale loaded weakly on latent pain. Although pain and depression are linked, we found that affective pain is distinct from depression, and that somatic depression is distinct from pain. This finding justifies further examination of the casual relationship between pain and depression.
Asunto(s)
Depresión/complicaciones , Depresión/psicología , Dolor/complicaciones , Dolor/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Depresión/diagnóstico , Análisis Factorial , Femenino , Humanos , Israel , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dimensión del Dolor , Autoevaluación (Psicología) , Trastornos Somatomorfos/psicología , Adulto JovenRESUMEN
UNLABELLED: The experience of pain is influenced by patients' personality, social and cultural background, and patient-doctor interaction. This study examines the role of self-reported pain, pain diagnosis, age, gender, depression, and the personality trait of self-criticism (defined as individuals' tendency to set unrealistically high self-standards and to adopt a punitive stance toward one's self), in determining physicians' view of expected prognosis in response to chronic pain management. Before the first visit to a tertiary chronic pain clinic, patients provided information regarding their perceived pain, depression, and self-criticism. Immediately subsequent to the visit, physicians' evaluated expected prognosis. Participating physicians were blinded to the patient's psychosocial variables collected. Sixty-four patients with chronic pain (34 women and 30 men) with various diagnoses were included. Patients' age, gender, pain diagnosis, self-reported pain, and depression did not significantly correlate with physician's estimation of expected prognosis. In contrast, patients' self-criticism emerged as an independent predictor of physicians' pessimism regarding outcome. Thus, in the chronic pain clinic setting, patients' personality, rather than self-reported pain experience, determines doctor's clinical judgment of expected prognosis. PERSPECTIVE: Chronic pain is a multimodal negative experience that is determined by physiological, cognitive, personological, and interpersonal factors. In line with this observation, we found patients' personality, specifically, their self-criticism, determines physicians' clinical judgment of expected prognosis.
Asunto(s)
Dimensión del Dolor , Dolor/diagnóstico , Dolor/psicología , Relaciones Médico-Paciente , Médicos/psicología , Autoimagen , Enfermedad Crónica , Depresión/etiología , Femenino , Humanos , Masculino , Dolor/complicaciones , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Our purpose was to reassess the effectiveness of phenol 4% in aqueous solution for neurolysis in patients with severe chronic nonmalignant pain syndromes who did not achieve adequate pain control (visual analog scale [VAS] Asunto(s)
Manejo del Dolor
, Fenol
, Simpaticolíticos
, Adulto
, Anciano
, Anciano de 80 o más Años
, Enfermedad Crónica
, Medios de Contraste
, Femenino
, Fluoroscopía
, Estudios de Seguimiento
, Humanos
, Yopamidol
, Masculino
, Persona de Mediana Edad
, Dolor/diagnóstico
, Dimensión del Dolor
, Estudios Prospectivos
RESUMEN
BACKGROUND: The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. OBJECTIVE: The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. METHODS: A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. RESULTS: Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. CONCLUSIONS: A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.
Asunto(s)
Analgésicos Opioides/efectos adversos , Oxicodona/efectos adversos , Convulsiones/inducido químicamente , Analgésicos Opioides/administración & dosificación , Preparaciones de Acción Retardada , Cefalea/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificaciónRESUMEN
Clonidine is frequently added to opioids in implantable intrathecal pumps for the management of chronic pain. In such devices, a small non-retrievable volume is always present in the reservoir, and its effect on drug stability is unknown. Furthermore, stability of clonidine, when mixed with hydromorphone, has not been previously determined. This study examined the stability of clonidine when co-administered with hydromorphone in implanted intrathecal pumps. Samples of hydromorphone-clonidine before pump refill and from residual solution at subsequent refill were obtained from chronic pain patients. Clonidine concentration was measured using HPLC. Twenty paired samples from 3 patients were analyzed. All 3 patients had a SynchroMed pump implanted for 3-5 years. We found no loss in clonidine concentration during the time between refills (35 +/- 13 days), and no correlation between clonidine concentration and time interval between refills. In conclusion, clonidine, mixed with hydromorphone, is stable when delivered by implantable intrathecal pump for long-term use.
Asunto(s)
Clonidina/administración & dosificación , Clonidina/análisis , Estabilidad de Medicamentos , Hidromorfona/administración & dosificación , Hidromorfona/análisis , Bombas de Infusión Implantables , Inyecciones Espinales/métodos , Dolor/tratamiento farmacológico , Analgésicos/administración & dosificación , Analgésicos/análisis , Enfermedad Crónica , Mezclas Complejas/administración & dosificación , Mezclas Complejas/análisis , Combinación de Medicamentos , Almacenaje de Medicamentos/métodos , Humanos , Garantía de la Calidad de Atención de Salud/métodosRESUMEN
OBJECTIVE: To evaluate the effectiveness of dronabinol for the treatment of neuropathic pain refractory to previous treatment. METHODS: We studied the response (reduction of pain intensity and functional improvement) to dronabinol (5 mg/day to 25 mg/day) in two adolescents with neuropathic pain and depression refractory to previous treatments over two and five years, respectively. RESULTS: Reduction in pain intensity (45%) was achieved in patient 2 and was unchanged in patient 1. Functional improvement was markedly increased in terms of academic performance, mood and sleep in both patients over four to five months, without major adverse effects. While these improvements dissipated over time, the patients were more reconnected with rehabilitation and focused less on the intrusiveness of their pain problem in their every day lives. CONCLUSIONS: Dronabinol appeared to be effective in improving pain affect and psychosocial functioning in the treatment of refractory neuropathic pain and may be considered as an adjuvant medication in the rehabilitation process. Well-controlled placebo studies are required for further evaluation.
Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Dronabinol/uso terapéutico , Dolor/tratamiento farmacológico , Adolescente , Enfermedad Crónica , Femenino , Humanos , Masculino , Dimensión del Dolor/efectos de los fármacos , Resultado del TratamientoRESUMEN
OBJECTIVE: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B(2) receptors improves neurological status after brain injury, but the effect of B(2) antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B(2) receptor antagonist, on brain tissue PGE(2) after closed head trauma (CHT). METHODS: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE(2) (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. RESULTS: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE(2) (77.7+/-65.9 pg/mg tissue, mean+/-SD) was less than in the group receiving CHT+saline (368.1+/-186.2 pg/mg tissue) and not different than sham+saline (78.7+/-30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. CONCLUSION: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE(2) increase in injured brain tissue.
Asunto(s)
Encéfalo/efectos de los fármacos , Dinoprostona/biosíntesis , Traumatismos Cerrados de la Cabeza/metabolismo , Quinolinas/farmacología , Animales , Antagonistas de los Receptores de Bradiquinina , Encéfalo/metabolismo , Técnicas de Cultivo , Dinoprostona/análisis , Modelos Animales de Enfermedad , Presión Intracraneal/efectos de los fármacos , Masculino , Análisis Multivariante , Probabilidad , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Estadísticas no ParamétricasRESUMEN
Bradykinin is an endogenous inflammatory agent that enhances vascular permeability and produces tissue edema. We investigated whether LF 16-0687 Ms, a potent nonpeptide antagonist of bradykinin type-2 (B(2)) receptor, was able to reduce brain swelling and to improve the recovery of neurological function following closed head trauma (CHT) in rats. In dose-effect studies, LF 16-0687 Ms doses of 0.75-4.5 mg/kg given 1 h after trauma significantly reduced the development of edema in the injured hemisphere by a maximum of 70%. It had no effect on the brain water content of sham-operated rats. LF 16-0687 Ms also significantly improved neurological recovery evaluated by a Neurological Severity Score (NSS) based on motor, reflex, and behavioral tests. In time-window studies LF 16-0687 Ms (2.25 mg/kg) was given 1, 2, 4, and 10 h after CHT. The extent of edema was significantly reduced when LF 16-0687 Ms was given 1 h (-45%), 2 h (-52%), and 4 h (-63%) but not 10 h (-24%) after CHT. Given at any time-point, LF 16-0687 Ms significantly improved the recovery of the NSS at 24 h. In duration of treatment studies, rats tended to recover normal neurological function over 14 days after CHT. However, time to recovery was longer in severely than in moderately injured animals, unless they were treated with LF 16-0687 Ms. This study provides further evidence that blockade of bradykinin B(2) receptors represents a potential effective approach to the treatment of focal cerebral contusions.