RESUMO
Long-term potentiation (LTP) is a persistent increase in synaptic strength required for many behavioral adaptations, including learning and memory, visual and somatosensory system functional development, and drug addiction. Recent work has suggested a role for LTP-like phenomena in the processing of nociceptive information in the dorsal horn and in the generation of central sensitization during chronic pain states. Whereas LTP of glutamatergic and GABAergic synapses has been characterized throughout the central nervous system, to our knowledge there have been no reports of LTP at mammalian glycinergic synapses. Glycine receptors (GlyRs) are structurally related to GABAA receptors and have a similar inhibitory role. Here we report that in the superficial dorsal horn of the spinal cord, glycinergic synapses on inhibitory GABAergic neurons exhibit LTP, occurring rapidly after exposure to the inflammatory cytokine interleukin-1 beta. This form of LTP (GlyR LTP) results from an increase in the number and/or change in biophysical properties of postsynaptic glycine receptors. Notably, formalin-induced peripheral inflammation in vivo potentiates glycinergic synapses on dorsal horn neurons, suggesting that GlyR LTP is triggered during inflammatory peripheral injury. Our results define a previously unidentified mechanism that could disinhibit neurons transmitting nociceptive information and may represent a useful therapeutic target for the treatment of pain.
Assuntos
Glicina/metabolismo , Interleucina-1beta/fisiologia , Potenciação de Longa Duração/fisiologia , Neuralgia/fisiopatologia , Células do Corno Posterior/fisiologia , Sinapses/fisiologia , Animais , Comportamento Animal/fisiologia , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Interneurônios/metabolismo , Interneurônios/fisiologia , Potenciação de Longa Duração/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuralgia/metabolismo , Neurite (Inflamação)/metabolismo , Neurite (Inflamação)/fisiopatologia , Técnicas de Cultura de Órgãos , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Transdução de Sinais/fisiologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologiaRESUMO
BACKGROUND: Young adult sexual minority women (SMW) have unique sexual health needs and higher rates of some poor sexual health outcomes compared to their heterosexual peers. Unequal access to relevant sexual health information may contribute to sexual orientation disparities in sexual health among women, but research on sexual health communication among SMW is sparse. METHODS: In-depth interviews conducted in 2016-2017 investigated sexual health communication in a sample of 29 racially/ethnically diverse cisgender women and non-binary individuals assigned female at birth who were between 19 and 36 years of age and identified as a sexual minority. Data were analyzed using a thematic analysis approach that involved inductive and deductive coding to identify themes. RESULTS: Three broad themes were identified: 1) sources of sexual health information; 2) sexual health information needs; and 3) preferences for sexual health information delivery. Participants discussed and critiqued the Internet, other mass media, health care providers, school-based sex education, family, and peers/partners as sources of sexual health information. Participants expressed a need for customized, non-heteronormative information pertaining to sexually transmitted infection risk and prevention. They preferred receiving information from health care providers, the Internet, and other mass media, and some also suggested school-based sex education and peer education as methods for delivering information. CONCLUSIONS: Participants expressed clear desires for relevant, high-quality sexual health information delivered through a variety of channels, especially the Internet, other mass media, and health care providers. POLICY IMPLICATIONS: Findings call for policies that improve provision of sexual health information through health care providers, online resources, and school-based sex education.
RESUMO
BACKGROUND: Health care providers are an important source of sexually transmitted infection (STI) prevention information for young adult sexual minority women (SMW). However, very few studies have described patient-provider STI communication in this understudied and underserved population. We explore sexual minority women's experiences communicating with health care providers about sexual health, with particular attention to STI prevention, to inform programs and practices that address their unique needs and concerns. METHODS: We conducted 29 in-depth interviews with sexual minority cisgender women and nonbinary assigned female at birth (AFAB) individuals aged 18-36 years. The sample included White (55%), Asian (31%), Black (17.2%), and Latina (3.4%) participants. We used thematic analysis with deductive and inductive coding to identify themes related to patient-provider STI prevention communication. RESULTS: Heteronormative health care provider assumptions inhibited participants' willingness to disclose their sexual orientation and discuss sexual health issues with providers. Most sexual health conversations focused on pregnancy and contraception, which many felt was irrelevant to them, and limited STI prevention recommendations to condom use. Participants reported that some providers lacked medical knowledge on AFAB-to-AFAB STI transmission and were not able to provide relevant STI prevention information. Providers' bias related to gender identity and race/ethnicity furthered some participants' mistrust generated from providers' heteronormative assumptions. CONCLUSIONS: Our study describes several barriers that AFAB sexual minorities felt inhibited their patient-provider sexual health communication. Interventions are needed to improve patient-provider STI prevention conversations with AFAB sexual minorities so they can access the sexual health information they need to effectively protect themselves from STIs.
Assuntos
Atitude do Pessoal de Saúde , Comunicação , Pessoal de Saúde/psicologia , Homossexualidade Feminina/psicologia , Minorias Sexuais e de Gênero/psicologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Massachusetts , Gravidez , Pesquisa Qualitativa , Saúde Sexual , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
CONTEXT: Some sexual minority women may be less likely than other women to engage in human papillomavirus (HPV) prevention behaviors. Although risk perceptions have been found to be associated with health behaviors, HPV risk perceptions among U.S. sexual minority women have not been examined. METHODS: In 2016-2017, in-depth interviews were conducted in Boston with 29 sexual minority individuals aged 18-36 who were assigned female at birth (AFAB) and identified as women or nonbinary. Purposive sampling was used to recruit participants online, through community-based and student organizations, and by word of mouth. Thematic analysis was employed to examine participants' HPV risk perceptions. RESULTS: Participants incorrectly linked HPV risk to the exchange of genital fluids, and a hierarchy of perceived risk emerged in relation to sexual orientation: Individuals who engage in penile-vaginal sex with partners who were assigned male at birth (AMAB) were perceived to be at highest risk, and lesbians and individuals with only AFAB partners were perceived to be at low risk. Lesbians and participants with only AFAB partners identified sex with bisexual women or AFAB individuals with AMAB partners as a risk factor for HPV infection. Risk perceptions were shaped by health care providers' linking HPV risk to sex with AMAB individuals, a lack of discussion of HPV with parents and peers, and the exclusion of information on HPV and sexual minority women from school-based sex education. CONCLUSION: Interventions providing sexual minority AFAB individuals with comprehensive, accurate and tailored information about HPV risk are needed.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/epidemiologia , Minorias Sexuais e de Gênero , Adolescente , Adulto , Feminino , Pessoal de Saúde , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Educação de Pacientes como Assunto , Risco , Comportamento Sexual , Pessoas Transgênero , Adulto JovemRESUMO
BACKGROUND: Dopaminergic neurons in the ventral tegmental area of the brain are an important site of convergence of drugs and stress. We previously identified a form of long-term potentiation of gamma-aminobutyric acid (GABA)ergic synapses on these neurons (LTPGABA). Our studies have shown that exposure to acute stress blocks this LTP and that reversal of the block of LTPGABA is correlated with prevention of stress-induced reinstatement of cocaine-seeking behavior. METHODS: Sprague-Dawley rats were subjected to cold-water swim stress. Midbrain slices were prepared following stress, and whole-cell patch clamp recordings of inhibitory postsynaptic currents were performed from ventral tegmental area dopamine neurons. Antagonists of glucocorticoid receptors and kappa opioid receptors (κORs) were administered at varying time points after stress. Additionally, the ability of a kappa antagonist administered following stress to block forced swim stress-induced reinstatement of cocaine self-administration was tested. RESULTS: We found that an acute stressor blocks LTPGABA for 5 days after stress through a transient activation of glucocorticoid receptors and more lasting contribution of κORs. Even pharmacological block of κORs beginning 4 days after stress has occurred reversed the block of LTPGABA. Administration of a κORs antagonist following stress prevents reinstatement of cocaine-seeking behavior. CONCLUSIONS: A brief stressor produces changes in the reward circuitry lasting several days. Our findings reveal roles for glucocorticoid receptors and κORs as mediators of the lasting effects of stress on synaptic plasticity. κORs antagonists reverse the neuroadaptations underlying stress-induced drug-seeking behavior and may be useful in the treatment of cocaine addiction.