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1.
BMC Med Ethics ; 22(1): 17, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622293

RESUMO

BACKGROUND: Advances in biomedicine can substantially change human life. However, progress is not always followed by ethical reflection on its consequences or scientists' responsibility for their creations. The humanities can help health sciences students learn to critically analyse these issues; in particular, literature can aid discussions about ethical principles in biomedical research. Mary Shelley's Frankenstein; or, the modern Prometheus (1818) is an example of a classic novel presenting complex scenarios that could be used to stimulate discussion. MAIN TEXT: Within the framework of the 200th anniversary of the novel, we searched PubMed to identify works that explore and discuss its value in teaching health sciences. Our search yielded 56 articles, but only two of these reported empirical findings. Our analysis of these articles identified three main approaches to using Frankenstein in teaching health sciences: discussing the relationship between literature and science, analysing ethical issues in biomedical research, and examining the importance of empathy and compassion in healthcare and research. After a critical discussion of the articles, we propose using Frankenstein as a teaching tool to prompt students to critically analyse ethical aspects of scientific and technological progress, the need for compassion and empathy in medical research, and scientists' responsibility for their discoveries. CONCLUSION: Frankenstein can help students reflect on the personal and social limits of science, the connection between curiosity and scientific progress, and scientists' responsibilities. Its potential usefulness in teaching derives from the interconnectedness of science, ethics, and compassion. Frankenstein can be a useful tool for analysing bioethical issues related to scientific and technological advances, such as artificial intelligence, genetic engineering, and cloning. Empirical studies measuring learning outcomes are necessary to confirm the usefulness of this approach.


Assuntos
Pesquisa Biomédica , Medicina na Literatura , Inteligência Artificial , Humanos , Princípios Morais , Tecnologia
2.
BMC Med Educ ; 21(1): 509, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565375

RESUMO

BACKGROUND: Medical dramas have been popular since their inception, especially among medical students. We hypothesized that the recent increase in the availability of TV medical series through online streaming platforms has probably changed health science students' viewing habits as well as the representation of bioethical conflicts and health professionals. METHODS: We invited undergraduate students of medicine, nursing, and human biology to complete a self-administered questionnaire about their viewing habits and perceptions of the depictions of bioethical issues and professionalism in TV medical series. RESULTS: Of the 355 respondents, 98.6 % had watched TV in the last year, 93.5 % watched TV series, and 49.6 % watched medical dramas more than once a week. The most-viewed medical dramas were The Good Doctor, House MD, and Grey's Anatomy. The most-remembered bioethical topics were medical errors, inappropriate professional behaviors, and death. Most students considered that ideals of professionalism were depicted positively and professionals were portrayed as intelligent, professionally qualified, and competent. CONCLUSIONS: Medical dramas are very popular with health science students and are potentially useful as teaching tools for discussing issues related to bioethics and professionalism.


Assuntos
Bioética , Drama , Estudantes de Medicina , Hábitos , Humanos , Profissionalismo , Televisão
3.
J Perianesth Nurs ; 36(5): 553-558, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33966992

RESUMO

PURPOSE: The purpose of this study was to classify elements of patients' discomfort in the resuscitation room after open or laparoscopic abdominal surgery as per health care professionals' perceptions. DESIGN: A prospective cross-sectional study at a tertiary hospital in Spain. METHODS: Resuscitation room nurses administered the Postoperative Discomfort Inventory to physicians and nurses with >1 year experience working closely with patients who had undergone abdominal surgery, asking them to score nine items related to patients' discomfort in the first 8 hours after surgery on an 11-point scale (0 = absent to 10 = very severe). Interobserver agreement among proxy reporters was measured with the Spearman's ρ; correlations >0.35 was considered adequate agreement. FINDINGS: Of 125 eligible professionals, 116 (93%) participated (63 [54%] nurses and 53 [46%] physicians; mean age, 38 ± 12 years; 86 [74%] women). Professionals' perception of discomfort differed significantly between patients undergoing open surgery and those undergoing laparoscopic surgery; after open surgery, the most common types were pain (7.1 ± 1.8), movement restriction (7 ± 1.75), and dry mouth (6.6 ± 2.6), whereas after laparoscopic surgery, the most common types were dry mouth (5.85 ± 2.8), abdominal bloating (5.3 ± 2.5), and pain (5 ± 2.2). The Spearman's ρ correlations were inadequate for all items except for dry mouth in open surgery (r = 0.40). CONCLUSIONS: Pain, movement restriction, abdominal bloating, and dry mouth were the main causes of discomfort. Our findings highlight the need to be vigilant for all manifestations of discomfort after abdominal surgery to enable timely treatment.


Assuntos
Abdome , Pessoal de Saúde , Abdome/cirurgia , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos
4.
Eur J Clin Pharmacol ; 76(12): 1653-1658, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32886177

RESUMO

PURPOSE: Feature films are increasingly being used in teaching health sciences. However, few publications address the effectiveness of this approach. We hypothesized that using feature films could help students learn. We aimed to assess the effectiveness of using a feature film to teach students about adverse drug reactions and pharmacovigilance. METHODS: The study population comprised third-, fifth-, and sixth-year undergraduate students of medicine, third-year undergraduate students of human biology, and graduate students in a master's degree program about the pharmaceutical and biotechnology industry. Students watched clips from the film 150 Miligrams (La fille de Brest) and discussed them afterward. To measure learning, we administered a 10-question multiple-choice test about pharmacovigilance concepts. We assessed students' satisfaction with the activity through a questionnaire. An exploratory comparative analysis was performed. RESULTS: A total of 237 students participated. Postintervention assessment scores were significantly higher than preintervention scores for the entire population and for all subgroups. The mean number of correct answers was 4.41 on the preintervention assessment and 5.78 on the postintervention assessment (mean gain: 1.37; 95% CI: 1.10-1.65). Similar results were found when analyzing groups of students from each group. Student satisfaction with this teaching activity was high in all groups. CONCLUSIONS: Cinemeducation is a useful tool for teaching about adverse drug reactions and pharmacovigilance processes. Most students were highly satisfied.


Assuntos
Instrução por Computador/métodos , Educação de Graduação em Medicina/métodos , Filmes Cinematográficos , Farmacologia Clínica/educação , Farmacovigilância , Biologia/educação , Biotecnologia/educação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Avaliação Educacional/estatística & dados numéricos , Estudos de Viabilidade , Humanos , Aprendizagem , Satisfação Pessoal , Projetos Piloto , Estudos Prospectivos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Estudantes de Farmácia/psicologia , Estudantes de Farmácia/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos
5.
Dermatology ; 236(3): 255-261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31694025

RESUMO

BACKGROUND/AIMS: The term vulvodynia refers to vulvar pain of unknown origin lasting at least 3 months. Psychiatric comorbidities are a common feature and, along with pain, may severely affect patients' wellbeing. We aimed to determine the characteristics of pain in vulvodynia, to correlate characteristics with symptoms of anxiety and depression, and to analyse the impact of these factors on patients' quality of life. METHODS: This cross-sectional observational study analysed pain, anxiety, and depression and the effects of these factors on quality of life. Pain, anxiety, and depression were assessed using validated tools in 110 women. RESULTS: Statistical analyses found correlations between pain and anxiety and between anxiety and worsened quality of life. Patients often reported stinging, burning, pain, itching, and dyspareunia, pointing to the importance of temporal, localisation, punctate pressure, thermal, tactile sensitivity, and emotional tension characteristics. Most patients had severe pain related to psychiatric comorbidities and decreased quality of life. CONCLUSION: Using descriptors of pain quality and assessing anxiety and depression might help to define subgroups of patients that may benefit from different therapeutic approaches and thus enable treatments to be tailored to individual patients.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Qualidade de Vida , Vulvodinia/epidemiologia , Vulvodinia/psicologia , Adaptação Psicológica , Adulto , Idoso , Ansiedade/etiologia , Comorbidade , Estudos Transversais , Depressão/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Vulvodinia/complicações , Adulto Jovem
6.
Sci Eng Ethics ; 26(5): 2791-2808, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533445

RESUMO

Two hundred years after it was first published, Mary Shelley's Frankenstein; or, the modern Prometheus remains relevant. This novel has endured because of its literary merits and because its themes lend themselves to analysis from multiple viewpoints. Scholars from many disciplines have examined this work in relation to controversial scientific research. In this paper, we review the academic literature where Frankenstein is used to discuss ethics, bioethics, science, technology and medicine. We searched the academic literature and carried out a content analysis of articles discussing the novel and films derived from it, analyzing the findings qualitatively and quantitatively. We recorded the following variables: year and language of publication, whether it referred to the novel or to a film, the academic discipline in which it was published, and the topics addressed in the analysis. Our findings indicate that the scientific literature on Frankenstein focuses mainly on science and the personality of the scientist rather than on the creature the scientist created or ethical aspects of his research. The scientist's responsibility is central to the ethical interest of Frankenstein; this issue entails both the motivation underlying the scientist's acts and the consequences of these acts.


Assuntos
Literatura Moderna , Medicina na Literatura , Humanos , Princípios Morais , Tecnologia
7.
BMC Med Educ ; 19(1): 134, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068154

RESUMO

BACKGROUND: Biomedicine needs innovative professionals. Inquiry-based learning (IBL) aims to develop higher order thinking skills, such as creativity and research. Stimulatory techniques and interprofessional education, which requires students from different fields to collaborate, also enhances creativity. In this study, the effectiveness of an interprofessional IBL course that introduces a creativity workshop based on stimulatory techniques to develop creative and research skills is examined. METHODS: 529 undergraduate human biology and medical students performed the interprofessional IBL course, 198 with the creativity workshop and 331 without. Students' perceptions of learning processes and outcomes were assessed in surveys and focus groups by the authors of this study. As well, the final learning results from both groups of students were analyzed by the teachers of the course and the researchers. RESULTS: The results show that the open IBL approach promoted the development of these skills, interprofessionality acted as a creativity enhancer and stimulatory techniques contributed to improve the learning outcomes. CONCLUSIONS: This study provides insight into how open interprofessional IBL fosters acquisition of complex skills and knowledge, pointing out the benefits and limitations of this approach in health sciences studies.


Assuntos
Pesquisa Biomédica/educação , Currículo , Educação de Graduação em Medicina/métodos , Educação , Aprendizagem Baseada em Problemas/métodos , Pesquisadores/educação , Estudantes de Medicina , Pensamento , Criatividade , Interpretação Estatística de Dados , Prática Clínica Baseada em Evidências , Humanos , Relações Interprofissionais , Modelos Educacionais
9.
J Adv Nurs ; 71(2): 441-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25168967

RESUMO

AIM: To compare the effectiveness and safety of fentanyl with placebo as pre-emptive treatment for pain associated with turning in patients in intensive care units. BACKGROUND: Turning is frequently a painful procedure in this setting. Pre-emptive administration of supplementary analgesia may help decrease this pain. However, medical literature on pre-emptive analgesia in these patients is scarce. DESIGN: A randomized, double-blind, controlled clinical trial. METHODS: This study will assess the benefits and risks of pre-emptive analgesia with fentanyl compared with placebo on turning-associated pain. Eighty patients will be recruited from among those older than 18 years and needing mechanical ventilation for at least 24 hours. Pain intensity will be assessed using the Behavioral Pain Scale. Primary outcome will be pain intensity between the baseline and 30 minutes after turning, measured by the area under the curve of the pain scale scores. Secondary outcomes will be the usefulness of physiological parameters and the Bispectral Index to measure pain and the safety of pre-emptive fentanyl in turning. The study protocol was approved in February 2011. DISCUSSION: If pre-emptive fentanyl is more effective than placebo and reasonably safe, the results of the current study may change nursing attitude in managing turning in critically ill patients. As a consequence, pain may be decreased during this nursing procedure.


Assuntos
Analgésicos Opioides/uso terapêutico , Fentanila/uso terapêutico , Movimentação e Reposicionamento de Pacientes/efeitos adversos , Dor/prevenção & controle , Respiração Artificial/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Adulto Jovem
10.
J Perianesth Nurs ; 30(4): 272-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26210558

RESUMO

PURPOSE: Patients who have surgery may experience distress in the following days. Although postoperative distress is a common experience, few studies have analyzed these patient complaints in-depth. The purpose of the present study was to analyze the potential causes of patients' discomfort after abdominal surgery. DESIGN: This was a prospective and observational study. METHODS: Patients (N = 131) were asked to rate their discomfort twice using a list of nine items in the first 6 to 8 hours after surgery and at 24 hours after its completion. Participants were asked to score intensity from 0 (absent) to 10 (unbearable). FINDINGS: The main causes of discomfort at 24 hours were pain (82%), movement restriction (79%), and dry mouth (70%). These items also had the highest scores (by gender, women scored higher than did men in insomnia, dry mouth, and abdominal distension). No significant differences were observed between patients who had undergone open or laparoscopic surgery. CONCLUSION: It was concluded that pain, movement restriction, and dry mouth were the most disturbing causes of discomfort. Therefore, symptoms other than pain should be considered to improve the well-being of patients after abdominal surgery.


Assuntos
Abdome/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Dor Pós-Operatória , Xerostomia , Adulto Jovem
11.
J Clin Nurs ; 23(9-10): 1421-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24720578

RESUMO

AIMS AND OBJECTIVES: To determine which unpleasant conditions might contribute to postoperative physical well-being, as judged by patients, nurses and physicians. BACKGROUND: Healthcare professionals have rarely assessed holistic postoperative well-being. Most studies have focused on specific symptoms, and a broader survey is lacking. DESIGN: A prospective study, which collected information on the causes of decreased physical well-being in the postoperative period. METHODS: The study was carried out in 101 patients who subsequently underwent elective surgery, in 82 physicians and in 40 nurses, all from the same hospital. A questionnaire was used for each sample, which included an inventory of 12 items, which have been associated with the worsening of postoperative physical well-being in the literature. Patients were asked to fill out the questionnaire on the second or third postoperative day and score each item from 0-10. RESULTS: Physicians rated pain (8·45), vomiting (6·68) and nausea (6·55) the highest. Nurses scored pain (8·48), nasogastric tube (7·13) and nausea (7·10) at the top. Insomnia and oxygen mask were scored significantly higher by nurses than by physicians. Patients scored pain (5·41) and movement restriction (4·62) the highest. When departments were compared, statistical differences were seen in nausea, vomiting, intravenous drips, nasogastric tube and oxygen mask. CONCLUSIONS: This survey shows that there is a general agreement between nurses and physicians regarding what contributes to decreased postoperative physical well-being, with few exceptions. However, healthcare professionals may differently rate some items that patients find as the most troubling. RELEVANCE TO CLINICAL PRACTICE: This survey shows that, besides pain, other symptoms can affect the physical well-being of patients during the postoperative period. Alleviation of some symptoms and the use of medical devices only when they are really needed may help to improve the well-being of patients.


Assuntos
Atitude do Pessoal de Saúde , Procedimentos Cirúrgicos Eletivos , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Dor Pós-Operatória/enfermagem , Médicos , Período Pós-Operatório , Estudos Prospectivos , Qualidade da Assistência à Saúde , Espanha , Inquéritos e Questionários
12.
PLoS One ; 19(4): e0301681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574095

RESUMO

Dopesick (2021) is the first TV series whose plot deals exclusively with the opioid crisis in the United States. The current study uses narrative analysis and framing theory to explore this series, discussing its portrayal of the people and themes involved in the opioid crisis. Our analysis found that although Dopesick attempts to portray multiple dimensions of the opioid crisis, its narrative oversimplifies the story in attributing the cause of the problem almost exclusively to Purdue Pharma and its director Richard Sackler, while downplaying other factors that contributed to the opioid crisis. Thus, the narrative in this TV series tends to offer simple explanations to a complex problem for which simple solutions are likely to be inadequate.


Assuntos
Narração , Epidemia de Opioides , Humanos , Estados Unidos , Analgésicos Opioides/efeitos adversos
13.
Nurse Educ Today ; 138: 106198, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38583344

RESUMO

BACKGROUND: Nursing students need to learn about sexually transmitted infections and preeclampsia. Cinenureducation is a rigorous method that uses materials from commercial movies or television series to teach health sciences students. OBJECTIVES: Using content analysis of the television series Call the Midwife, design a cinenureducation activity teaching nursing students about sexually transmitted infections and preeclampsia. Evaluate its effectiveness in knowledge acquisition. DESIGN, IMPLEMENTATION, AND PRE-POST ASSESSMENT OF KNOWLEDGE GAIN FOR TEACHING ACTIVITIES: The study comprised three main steps: designing the teaching activity, implementing it, and analyzing its pedagogical effectiveness through a pre-and-post study to assess knowledge acquisition resulting from the teaching activity. PARTICIPANTS: A six-member panel assessed the suitability of materials for the teaching goals. All second-year undergraduate nursing students in the course "Nursing management and leadership" at a nursing school in the 2022-2023 academic year were invited to participate (N = 160). METHODS: The panel conducted a content analysis of the first two seasons of the series to determine the usefulness of each episode for teaching the chosen topics. Students were randomly assigned to groups watching episodes emphasizing either sexually transmitted infections or preeclampsia, followed by discussion. Learning was gauged through a pre-post viewing 20-question multiple-choice test. Additionally, students' satisfaction was evaluated. RESULTS: A total of 142 nursing students participated. Significant differences between mean scores before and after intervention were found [6.90 vs. 6.42 on the preintervention assessment, p < 0.05; mean gain, 0.49 (95 % CI: 0.22-0.76)]. Most students were satisfied with the activity. CONCLUSIONS: The activity was useful for teaching about sexually transmitted infections and preeclampsia. The use of a television series portraying nurses enables the exploration of these critical topics. This has potential implications for integrating similar methods into nurse education curricula, emphasizing the broader impact of the research on pedagogical practices in healthcare education.


Assuntos
Filmes Cinematográficos , Pré-Eclâmpsia , Infecções Sexualmente Transmissíveis , Estudantes de Enfermagem , Humanos , Feminino , Infecções Sexualmente Transmissíveis/prevenção & controle , Estudantes de Enfermagem/estatística & dados numéricos , Estudantes de Enfermagem/psicologia , Gravidez , Pré-Eclâmpsia/enfermagem , Filmes Cinematográficos/estatística & dados numéricos , Bacharelado em Enfermagem/métodos , Tocologia/educação , Avaliação Educacional/métodos , Ensino/normas , Currículo , Adulto
15.
Croat Med J ; 51(6): 552-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21162168

RESUMO

AIM: To present the experience of running workshops for members of research ethics committees (REC) in Spain from 2001-2008 by a non-profit institution. METHODS: We analyzed data from 7 sessions of the course, involving 165 health professionals. Data were taken from an opinion survey conducted at the end of each seminar and a deferred questionnaire sent after the workshops. RESULTS: Opinions of 122 participants who completed the first questionnaire (84% of the 146 attendees) on these training courses were very positive (median, ≥ 4.5 out of 5). The second questionnaire was administered a few months after each session, and a total of 43 participants responded (36% of 118). The participants improved their knowledge, attitude, and skills (median, 4.0 out of 5) in most of the areas evaluated. Furthermore, they believed that training for REC members should be mandatory (median, 5.0 out of 5) and carried out regularly (median, 4.0 out of 5). The lack of communication between RECs and limitations in monitoring clinical trials (median, 4.5 out of 5) were the main problems according to respondents. Training was rated as a strong necessity (median, 4.0 out of 5). CONCLUSION: The courses were well received, they contributed to the overall learning of the participants, and served to highlight some of the major problems faced by REC members. These results emphasize the importance of training.


Assuntos
Pesquisa Biomédica/organização & administração , Currículo , Comitês de Ética em Pesquisa/organização & administração , Ética em Pesquisa/educação , Pesquisa Biomédica/ética , Pesquisa Biomédica/normas , Coleta de Dados , Escolaridade , Comitês de Ética em Pesquisa/normas , Comitês de Ética em Pesquisa/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Espanha , Estatísticas não Paramétricas , Inquéritos e Questionários
16.
Br J Pharmacol ; 177(5): 1187-1205, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31655493

RESUMO

BACKGROUND AND PURPOSE: Mu and delta opioid receptors(MOP, DOP) contribution to the manifestations of pathological pain is not understood. We used genetic approaches to investigate the opioid mechanisms modulating neuropathic pain and its comorbid manifestations. EXPERIMENTAL APPROACH: We generated conditional knockout mice with MOP or DOP deletion in sensoryNav1.8-positive neurons (Nav1.8), in GABAergic forebrain neurons (DLX5/6) orconstitutively (CMV). Mutant mice and wild-type littermates were subjected topartial sciatic nerve ligation (PSNL) or sham surgery and their nociception wascompared. Anxiety-, depressivelike behaviour and cognitive performance were also measured. Opioid receptor mRNA expression, microgliosis and astrocytosis were assessed in the dorsalroot ganglia (DRG) and/or the spinal cord (SC). KEY RESULTS: Constitutive CMV-MOP knockouts after PSNL displayed reduced mechanical allodynia and enhanced heat hyperalgesia. This phenotype was accompanied by increased DOP expression in DRG and SC, and reduced microgliosis and astrocytosis in deep dorsal horn laminae. Conditional MOP knockouts and control mice developed similar hypersensitivity after PSNL, except for anenhanced heat hyperalgesia by DLX5/6-MOP male mice. Neuropathic pain-induced anxiety was aggravated in CMV-MOP and DLX5/6-MOP knockouts. Nerve-injured CMV-DOP mice showed increased mechanical allodynia, whereas Nav1.8-DOP and DLX5/8-DOP mice had partial nociceptive enhancement. CMV-DOP and DLX5/6-DOP mutants showed increased depressive-like behaviour after PSNL. CONCLUSIONS AND IMPLICATIONS: MOP activity after nerve injury increased anxiety-like responses involving forebrain GABAergic neurons and enhanced mechanical pain sensitivity along with repression of DOP expression and spinal cord gliosis. In contrast, DOP shows a protective function limiting nociceptive and affective manifestations of neuropathic pain.


Assuntos
Nociceptividade , Receptores Opioides delta , Animais , Hiperalgesia , Masculino , Camundongos , Camundongos Mutantes Neurológicos , Receptores Opioides , Receptores Opioides delta/genética , Receptores Opioides mu/genética
17.
J Neurosci ; 28(46): 12125-35, 2008 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19005077

RESUMO

Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB(2) cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB(2) knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB(2) receptors. These results demonstrate the crucial role of CB(2) cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB(2) knock-outs, thus demonstrating the implication of the CB(2) receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.


Assuntos
Neuralgia/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Receptor CB2 de Canabinoide/imunologia , Medula Espinal/imunologia , Animais , Astrócitos/imunologia , Astrócitos/metabolismo , Transplante de Medula Óssea , Modelos Animais de Doenças , Feminino , Gliose/imunologia , Gliose/metabolismo , Gliose/fisiopatologia , Células-Tronco Hematopoéticas/imunologia , Hiperalgesia/imunologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Microglia/imunologia , Microglia/metabolismo , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Células do Corno Posterior/imunologia , Células do Corno Posterior/patologia , Células do Corno Posterior/fisiopatologia , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Neuropatia Ciática/imunologia , Neuropatia Ciática/metabolismo , Neuropatia Ciática/fisiopatologia , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia
18.
J Neurosci ; 28(46): 12136-45, 2008 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19005078

RESUMO

Nerve injuries often lead to neuropathic pain syndrome. The mechanisms contributing to this syndrome involve local inflammatory responses, activation of glia cells, and changes in the plasticity of neuronal nociceptive pathways. Cannabinoid CB(2) receptors contribute to the local containment of neuropathic pain by modulating glial activation in response to nerve injury. Thus, neuropathic pain spreads in mice lacking CB(2) receptors beyond the site of nerve injury. To further investigate the mechanisms leading to the enhanced manifestation of neuropathic pain, we have established expression profiles of spinal cord tissues from wild-type and CB(2)-deficient mice after nerve injury. An enhanced interferon-gamma (IFN-gamma) response was revealed in the absence of CB(2) signaling. Immunofluorescence stainings demonstrated an IFN-gamma production by astrocytes and neurons ispilateral to the nerve injury in wild-type animals. In contrast, CB(2)-deficient mice showed neuronal and astrocytic IFN-gamma immunoreactivity also in the contralateral region, thus matching the pattern of nociceptive hypersensitivity in these animals. Experiments in BV-2 microglia cells revealed that transcriptional changes induced by IFN-gamma in two key elements for neuropathic pain development, iNOS (inducible nitric oxide synthase) and CCR2, are modulated by CB(2) receptor signaling. The most direct support for a functional involvement of IFN-gamma as a mediator of CB(2) signaling was obtained with a double knock-out mouse strain deficient in CB(2) receptors and IFN-gamma. These animals no longer show the enhanced manifestations of neuropathic pain observed in CB(2) knock-outs. These data clearly demonstrate that the CB(2) receptor-mediated control of neuropathic pain is IFN-gamma dependent.


Assuntos
Interferon gama/imunologia , Neuralgia/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Receptor CB2 de Canabinoide/imunologia , Transdução de Sinais/imunologia , Medula Espinal/imunologia , Animais , Astrócitos/imunologia , Células Cultivadas , Técnicas de Inativação de Genes/métodos , Hiperalgesia/imunologia , Hiperalgesia/fisiopatologia , Interferon gama/genética , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , Neuralgia/genética , Neuralgia/metabolismo , Neurônios/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismos dos Nervos Periféricos , Nervos Periféricos/imunologia , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Receptores CCR2/imunologia , Receptores CCR2/metabolismo , Transdução de Sinais/genética , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Regulação para Cima/imunologia
19.
Int J Neurosci ; 119(2): 185-203, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19125373

RESUMO

Endoneurial nerve growth factor (30 ng) produced significant heat hyperalgesia in rats on postinjection days 3 and 5. The percentage of neuron profiles expressing the sensory neuropeptide substance P in the dorsal root ganglion (DRG), and the density and distribution of substance P immunoreactivity at the DRG and the dorsal horn remained essentially unchanged throughout the 10 days of study. NGF increased pain scores in the second phase of the formalin test on postinjection day 3, but not on days 5 and 10. Our results indicate that the observed heat hyperalgesia is not dependent on NGF-induced changes in SP content and release from primary sensory neurons.


Assuntos
Hiperalgesia/metabolismo , Fator de Crescimento Neural/metabolismo , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Substância P/metabolismo , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Animais , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Imuno-Histoquímica , Masculino , Fator de Crescimento Neural/farmacologia , Nociceptores/efeitos dos fármacos , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/efeitos dos fármacos
20.
Eur J Pain ; 23(3): 435-454, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30318675

RESUMO

Injury to peripheral nerves often leads to abnormal pain states (hyperalgesia, allodynia and spontaneous pain), which can remain long after the injury heals. Although opioid agonists remain the gold standard for the treatment of moderate to severe pain, they show reduced efficacy against neuropathic pain. In addition to analgesia, opioid use is also associated with hyperalgesia and analgesia tolerance, whose underlying mechanisms share some commonalities with nerve injury-induced hypersensitivity. Here, we reviewed up-to-day research exploring the contribution of mu-opioid receptor (MOR) on the pathophysiology of neuropathic pain and on analgesic opioid actions under these conditions. We focused on the specific contributions of MOR populations at peripheral, spinal and supraspinal level. Moreover, evidences of neuroplastic changes that may underlie the low efficacy of MOR agonists under neuropathic pain conditions are reviewed and discussed. Sensitization processes leading to pain hypersensitivity, molecular changes in signalling pathways triggered by MOR and glial activation are some of these mechanisms elicited by both nerve injury and opioid exposure. Nerve injury-induced pain hypersensitivity might be masking the initial analgesic effects of opioid agonists, and alternatively, sustained opioid treatment to individuals already suffering from neuropathic pain could aggravate their pathophysiological state. Finally, some combined therapies that can increase opioid analgesic effectiveness in neuropathic pain treatment are highlighted. SIGNIFICANCE: This review provides evidence of the low benefit of opioid monotherapy in neuropathic pain and analyses the reasons of this reduced effectiveness. Opioid agonists along with drugs targeted to block the sensitization processes induced by MOR stimulation might result in a better management of neuropathic pain.


Assuntos
Analgésicos Opioides/farmacologia , Neuralgia/tratamento farmacológico , Receptores Opioides mu/agonistas , Humanos , Neuralgia/fisiopatologia
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