Dados da literatura indicam que os fumantes apresentam distúrbios psiquiátricos e psicológicos em maior frequência do que os não fumantes. Esses fatores podem contribuir para o início do tabagismo, bem como para sua manutenção, e induzir dificuldades no abandono. Entretanto, não existe na literatura nenhuma escala construída com a finalidade de avaliar as características emocionais de fumantes frente aos cigarros, de maneira simples e rápida. Este estudo teve como finalidade desenvolver uma escala que avaliasse o estado emocional geral dos fumantes em face ao uso do tabaco. Para tanto, fumantes que procuravam ambulatórios de cessação de tabagismo em hospitais públicos do Município de Ribeirão Preto foram submetidos a entrevistas padronizadas. Indivíduos não fumantes foram selecionados entre funcionários dessas mesmas instituições e entre acompanhantes e familiares dos fumantes. Inicialmente, níveis de Ansiedade, Depressão, Estresse Percebido, Autoestima e Solidão de um grupo de 120 fumantes (idade mediana: 54,6 anos; 74 mulheres) foram comparados com os de um grupo de 76 não fumantes (idade mediana: 45,5 anos; 47 mulheres). Os fumantes mostraram valores significantemente piores do que os não fumantes, em todas as medidas investigadas. Correlações entre os escores dessas medidas psicológicas, além da característica Apego aos Cigarros, foram feitas com as medidas do Teste de Dependência a Nicotina de Fagerström (TDNF) no grupo de fumantes. Os parâmetros psicológicos mostrando as melhores correlações com o TDNF foram selecionados para fazer parte de uma escala de 6 itens chamada Teste Emocional do Fumante (TEF). As pontuações do TEF deste grupo inicial e de uma amostra adicional de fumantes (n = 102; idade mediana= 52,6 anos; mulheres = 63) foram submetidas a análises psicométricas e testes de validação. O TEF mostrou uma estrutura consistente de dois fatores, ansiedade / depressão e apego aos cigarros. As pontuações de TEF apresentaram correlações significativas com o TDNF (r=0,418), número de cigarros defumados (r=0,299), tempo antes de sentir necessidade de um novo cigarro (r=-0,441) e prazer em fumar (r=0,346). A consistência interna do TEF foi maior do que a dos escores de TDNF (alfa de Cronbach: respectivamente 0,712 e 0,542). A confiabilidade teste-reteste do TEF foi excelente (coeficiente de correlação intraclasse=0,944). As pontuações de TEF superiores a 4 puderam distinguir fumantes de não fumantes com sensibilidade de 87,3% e especificidade de 92,7%. Pode-se concluir que o TEF é um instrumento simples que dá uma estimativa do status emocional relacionado ao tabagismo e pode definir um novo e valioso constructo da dependência do tabaco. O TEF tem potencial para se tornar uma ferramenta útil nas intervenções de cessação do tabagismo / Literature data show that smokers exhibit psychiatric and psychological abnormalities in higher frequency than non smokers. These factors may contribute to smoking beginning, as well as to its continuity, and bring obstacles for quitting. However, there is not in the literature any scale designed to evaluate the emotional features of smokers. This study aimed at developing a new scale to evaluate the overall emotional status of smokers in face of tobacco use. Smokers who look for treatment in public smoking cessation clinics of Ribeirão Preto city were submitted to standardized interviews. Non smokers were selected among workers from these facilities and companions and relatives from the smokers. Levels of Anxiety, Depression, Perceived Stress, Self Esteem, and Loneliness of a group of 120 smokers (median age: 54.6 years; 74 women) were compared with those of a group of 76 non smokers (median age: 45.5 years; 47 women). Smokers showed scores significantly worsen than non smokers regarding these measures. Correlations between these psychological scores, plus the feature Attachment to Cigarettes, and FTND counts were explored among smokers. Psychological features showing the best correlations with FTND were selected to be part of a 6 item scale called Smoker\'s Emotional Test (TEF). TEF scores of this initial group and of an additional sample of smokers (n=102; age= 52.6; women= 63) were submitted to psychometric analyses and validation tests. Results: TEF showed a consistent structure of two factors, Anxiety/Depression and Attachment to Cigarettes. TEF scores showed significant correlations with TDNF (r=0.418), number of smoked cigarettes (r=0.299), time to urge for a new cigarette (r=-0.441) and pleasure of smoking (r=0.346). The internal consistency of TEF was higher than that of FTND scores (Cronbach\'s alpha: respectively 0.712 and 0.542). The test-retest reliability of TEF was excellent (intraclass correlation coefficient=0.944). TEF scores higher than 4 could distinguish smokers from nonsmokers with sensitivity of 87.3% and specificity of 92.7%. In conclusion, TEF is a simple instrument that gives an estimative of smoking-related emotional status and may define a new valuable construct of tobacco addiction. TEF has the potential to become a useful tool in smoking cessation interventions.

Introdução: Fragilidade é uma síndrome clínica caracterizada pela diminuição da reserva de energia e pela resistência diminuída aos estressores, resultando em maior vulnerabilidade às condições adversas. A identificação do impacto causado pelo tabagismo na fragilidade permite uma melhor definição sobre a participação dos aspectos multidimensionais da síndrome e colabora na identificação de hábitos nocivos na proposta de abordagem terapêutica da fragilidade. Objetivo: Avaliar a associação entre tabagismo e fragilidade em idosos do município de São Paulo. Métodos: Estudo transversal de base populacional, com amostragem probabilística representativa, onde foram avaliados 1.413 pessoas com idade igual e superior a 60 anos em 2006. Foi adotado o fenótipo de fragilidade proposto por Fried e colaboradores (não frágil= nenhum componente, pré-frágil = 1 a 2 componentes; frágil = 3 ou mais componentes). O tabagismo foi mensurado em carga tabágica e status tabágico (fumante, ex fumante e não fumante). Os fatores associados foram obtidos por meio de análise do modelo de regressão logística multinomial a um nível de significância de 5 por cento no Stata/SE ® 10.0 for Windows. Resultados: Idosos fumantes apresentaram 1.54 vezes mais chance de serem pré-frágeis (p0,05). Foram identificados 14 por cento fumantes, 34,04 por cento ex-fumantes e 51,95 por cento não fumantes. Dentre os fumantes, 50,82 por cento estavam em processo de fragilização (4,35 por cento de frágeis e 46,47 por cento pré frágeis), enquanto que entre os não fumantes, 50,25 por cento estavam nesse processo (39,95 por cento pré-frágeis e 10,30 por cento frágeis). Conclusão: Foi encontrada associação significativa entre status tabágico e a condição de pré-fragilidade. Fumar não deve ser considerado uma forma eficaz de prevenir a fragilidade / Introduction: Frailty is a clinical syndrome characterized by decreased energy reserve and decreased resistance to stressors, resulting in increased vulnerability to adverse conditions. The identification of the impact caused by smoking in the fragility allows a better definition of the participation of the multidimensional aspects of the syndrome and collaborates in the identification of harmful habits in the proposal of a therapeutic approach to fragility. Objective: To evaluate an association between smoking and frailty in the elderly in São Paulo. Methods: This was a population-based, longitudinal observational study with representative probabilistic sampling, in which 1413 individuals aged 60 years or older were obtained in 2006. The frailty phenotype proposed by Fried et al. was used (non-frail = No component, pre-frail = 1 to 2 components; frail = 3 or more components). Smoking was measured in dose rate (pack-year) and smoking status (smoker, ex-smoker and non-smoker). The models were obtained through hierarchical logistic regression analysis and a significance level of 5 per cent in Stata / SE ® 10.0 for Windows. Results: Elderly smokers presented 1.54 times the chance of being pre-frail (p0.05). 14 per cent smokers, 34.04 per cent former smokers and 51.95 per cent non-smokers were identified. Among smokers, 50,82 per cent were in the frailty process (4,35 per cent frail and 46,47 per cent pre-frail), versus 50,25 per cent of non-smokers (10,30 per cent frail and 39,95 per cent pre-frail). Conclusion: There was an association between smoking status and pre-frailty. Smoking should not be considered an effective way to prevent frailty

Tobacco addiction is a leading preventable cause of death worldwide and places a heavy social and financial burden on society. There exists a substantial genetic variability in smoking behavior, the mechanisms of which are largely unknown. Despite significant advances in sequencing power, progress in the identification of genetic variants affecting smoking behavior based on human genome wide association studies has been slow. Thus this thesis investigates the utility of zebrafish as a model species in which to search for genetic variants affecting nicotine seeking. The work is based on the premise that as zebrafish are vertebrate with conserved neurochemical pathways and circuitry with humans, and the pathways involved in drug mediated reward and addiction are evolutionarily ancient, homologues of genes affecting zebrafish nicotine-seeking behavior will likely affect human smoking behavior. Thus results in zebrafish can be used to direct human genetic studies. The first result chapter addresses the hypothesis that zebrafish show conserved reward responses to common drugs of abuse. A conditioned place preference assay is used to assess zebrafish reward responses to stimulants, opioids, benzodiazepines and alcohol. The results indicate that, with the exception of benzodiazepines, reward responses are conserved, supporting the use of this model in a screen for genetic variants affecting nicotine preference. The second and third results chapters describe the findings of a pilot screen of ENU-mutagenized zebrafish provided by the Sanger Institute, Cambridge. I demonstrate that nicotine preference is heritable in fish as in Abstract 5 humans and identify 3 mutant lines that show increased or decreased nicotine place preference. Genotyping indicated that one of the families showing increased nicotine preference carries a predicted loss of function mutation in the slit3 gene. The involvement of this gene in nicotine preference was confirmed in a separate line. Further characterization of this line using qPCR showed slit3 mutants to have altered developmental expression of key nicotinic and dopaminergic genes. Having identified the slit3 gene as a locus affecting nicotine seeking in fish, I then tested the hypothesis that results in fish could be used to predict loci that affect human smoking behavior. Cohorts of patients were genotyped for 20 SNPs within the slit3 locus. Results of this analysis identified 1 novel SNP in the slit3 gene associated with smoking behavior in a cohort of individuals that were heavy smokers. This result was validated in cohorts of low and normal smoking prevalence. These data demonstrate the utility of behavioral assays in zebrafish to identify genes affecting human behavior and pave the way for the use of zebrafish to inform human studies exploring the genetic basis of drug seeking and behavioral disease.

Yeung, Chun Yiu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 53-62). / Abstracts in English and Chinese. / Abstract --- p.i / 論文摘要(Chinese Abstract) --- p.ii / Acknowledgements --- p.iii / List of Tables --- p.iv / Chapter Chapter 1: --- Introduction --- p.1 / Smoking: The greatest single preventable cause of death --- p.1 / Negative health impacts of smoking on non-smokers --- p.1 / Smoking ban in Hong Kong in 2007 --- p.2 / Lack of theory-based local smoking research --- p.3 / Self-Determination Theory --- p.4 / Extensions to current SDT research on smoking --- p.6 / Differentiating autonomous motivation in personal-relational dimension --- p.6 / Relational-interdependent self-construal and nature of autonomous motivation --- p.8 / Perceived competence and condition-specific self-efficacy --- p.9 / Proposed framework --- p.10 / Research purpose --- p.11 / Hypotheses --- p.11 / Statistical analyses --- p.12 / Chapter Chapter 2: --- Method --- p.14 / Recruitment strategies --- p.14 / Attrition of participants --- p.16 / Instruments --- p.16 / Variables of smoking pattern --- p.21 / Chapter Chapter 3: --- Results --- p.24 / Characteristics of participants --- p.24 / Attrition analysis --- p.25 / Descriptive statistics and construct score change from baseline to T2 assessment --- p.27 / Correlation analysis --- p.28 / Logistic regression for predicting quitters and non-quitters --- p.31 / Logistic regression for comparing the fundamental SDT and extended theoretical framework --- p.32 / Exploring the interaction effects between SDT variables and RISC in the prediction of quitting --- p.33 / ANOVAs on major variables for smokers with different quitting progress --- p.33 / "Additional analyses examining the differences in self-efficacy among quitters, quit attempters, and recalcitrant smokers" --- p.36 / Chapter Chapter 4: --- Discussion --- p.38 / Autonomous motivation and smoking cessation --- p.38 / Dilemma among health concerns and quitting behaviors --- p.39 / Possible priming effects in smoking cessation counseling sessions --- p.40 / Discrepancies in research design between the present study and previous SDT studies --- p.41 / Reflecting on the SDT and stages of health behavioral change --- p.42 / Findings related to proposed theoretical extensions --- p.43 / Relational autonomous motivation and RISC --- p.43 / Role of self-efficacy in smoking cessation: inspirations from process models of health behaviors --- p.44 / Recalcitrant smokers and their self-efficacy to respond to internal tempting conditions --- p.46 / Quit attempters and their self-efficacy to respond to external tempting conditions --- p.47 / Research limitations --- p.48 / Future directions and recommendations --- p.49 / References --- p.53

Background Women are less likely than men to successfully quit smoking when using NHS cessation services (The Information Centre, 2012, ICD, 2011). Methods The research used mixed methods and consisted of two studies. Study one was a secondary data analysis of service use data from cessation services in Glasgow, North Cumbria and Nottingham. The study examined whether women had lower cessation outcomes compared to men. Further analyses explored whether women using cessation support differed from men in terms of demographics, smoking behaviour, interpersonal characteristics or patterns of service use. The predictors of cessation success for women were identified. Study two consisted of 25 semi-structured interviews and 1 focus group (n=5) which explored women’s experiences of smoking, smoking cessation and NHS cessation support. Thematic analysis was used to analyse this data. Results Lower quit rates were observed for women in the English samples (4 weeks, 52.1% vs. 57.8%, 52 weeks, 12.7% vs. 17.2%) compared to men. Women experienced more markers of disadvantage compared to men. Disadvantage appeared to mediate smoking cessation outcomes in women by increasing nicotine addiction. Markers of nicotine dependence predicted smoking cessation outcomes in women. However, the qualitative investigation indicated that the emotional side of addiction also appeared to have an important role in the smoking behaviour for women. Variation existed in the preferred intensity of cessation support. However, knowledge of available cessation support options was low; suggesting that cessation services should ensure smokers make an informed choice about the format of cessation support they use. Conclusions The key finding of this thesis was that it highlighted that smoking and smoking cessation may be affected by the emotional role that smoking can have within women’s lives. Ways that NHS support could be altered to meet women’s needs are discussed within this thesis.

Tobacco smoke remains a major public health concern and a factor contributing to the development and progression of various lung diseases world-wide. Smoking cessation can significantly reduce the risk of developing smoking-related diseases, although some smokers remain at an elevated risk despite quitting. Here, I used high-throughput genomic technologies to pave the way for understanding the transcriptomic response in airway epithelium to tobacco exposure, smoking cessation and potentially reduced exposure products (PREP). First, using a longitudinal dataset of nasal airway epithelial cells obtained from active smokers enrolled in smoking cessation programs over 24 weeks, I demonstrated that tobacco-related alterations in the airway gene expression are rapidly reversed within 4 to 8 weeks following smoking cessation. Genes with different biological functions revert towards baseline with different dynamics following smoking cessation. These findings suggest that the nasal-epithelium can serve as a minimally-invasive site to measure the reversible impact of smoking. Secondly, using a dataset of nasal airway epithelial cells from active smokers who switched to potentially reduced exposure products (PREP) for 6 weeks, I showed that gene expression differences induced by switching to PREP may only constitute a partially reduced exposure relative to smoking cessation. My results demonstrate that the nasal-epithelium can also serve as a minimally-invasive site to measure the responses to PREP and may ultimately yield biomarkers to evaluate the potential disease risks associated with these products. Lastly, using small RNA-seq data from bronchial epithelial cells of smokers, I found alterations in airway micro-RNA expression that associate with time since quitting in former smokers. These studies have provided novel insights into the physiologic responses of the airway epithelium to tobacco smoke and PREP and may ultimately serve as a useful approach for evaluating the disease risks associated with changes in smoking behavior. This work sets the stage for additional studies aimed at identifying prevention strategies that decrease the persistent risk of smoking-related lung disease in former smokers and identify biomarkers to assess lung disease risk in former smokers. / 2016-12-31T00:00:00Z

Class of 2007 Abstract / Objectives: The purpose of this study was to examine the relationship between the demographics and attitudes of Arizona pharmacists regarding provision of smoking cessation services. Methods: Paper-based surveys were distributed to pharmacists attending the 2006 Arizona Pharmacy Alliance (AzPA) Annual Meeting in Tucson, Arizona. The instrument allowed collection of 12 demographic points from subjects for data cross-sectioning. Opinions of the pharmacists were collected for 35 statements of agreement level on a four-point Likert-type response scale. Association between the demographic and opinion variables was analyzed using either Kruskal-Wallis’ rank-sum or Spearman's correlation tests. Results: Of 350 surveys distributed, 78 subjects returned them and 63 (18%) met inclusion criteria. Respondents agreed to all barriers of smoking cessation, particularly lacks in time (82.5%), patient demand (79.7%), smoking cessation program availability (68%), and documentation system (56.6%). Participants’ demographics including age, gender, practice setting and position, time since completion of education, specific smoking cessation education received, time spent counseling a patient, and number of general and smoking cessation counsels were significantly associated with pharmacists’ perceived demand and resource barriers to provision of smoking cessation services, faith in a patient’s ability to quit or try, self-perception as a valuable and effective resource, comfort level approaching patients regarding smoking cessation, likelihood of intervention, and feelings of reward (all p-values < 0.05). Conclusions: This study identified several associations between pharmacists’ demographics and their thoughts towards provision of smoking cessation services, though causation is undetermined.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Cigarette smoke creates a molecular field of injury in epithelial cells that line the respiratory tract. We hypothesized that transcriptome sequencing (RNA-seq) will enhance our understanding of the field of molecular injury in response to tobacco smoke exposure and lung cancer pathogenesis by identifying gene expression differences not interrogated or accurately measured by microarrays. We sequenced the high- molecular weight fraction of total RNA (>200 nt) from pooled bronchial airway epithelial cell brushings (n = 3 patients per pool) obtained during bronchoscopy from healthy never smoker (NS) and current smoker (S) volunteers and smokers with (C) and without ( C) lung cancer undergoing lung nodule resection surgery. RNA-seq libraries were prepared using two distinct approaches, one capable of capturing non-polyadenylated RNA (the prototype NuGEN Ovation RNA-seq protocol) and the other designed to measure only polyadenylated RNA (the standard Illumina mRNA-seq protocol) followed by sequencing generating approximately 29 million 36 nt reads per pool and approximately 22 million 75 nt paired-end reads per pool, respectively. The NuGEN protocol captured additional transcripts not detected by the Illumina protocol at the expense of reduced coverage of polyadenylated transcripts, while longer read lengths and a paired-end sequencing strategy significantly improved the number of reads that could be aligned to the genome. The aligned reads derived from the two complementary protocols were used to define the compendium of genes expressed in the airway epithelium (n = 20,573 genes). Pathways related to the metabolism of xenobiotics by cytochrome P450, retinol metabolism, and oxidoreductase activity were enriched among genes differentially expressed in smokers, whereas chemokine signaling pathways, cytokine-cytokine receptor interactions, and cell adhesion molecules were enriched among genes differentially expressed in smokers with lung cancer. There was a significant correlation between the RNA-seq gene expression data and Affymetrix microarray data generated from the same samples (P < 0.001); however, the RNA-seq data detected additional smoking- and cancer-related transcripts whose expression was were either not interrogated by or was not found to be significantly altered when using microarrays, including smoking- related changes in the inflammatory genes SIOOA8 and SIOOA9 and cancer-related changes in MUC5AC and secretoglobin (SCGB3Al). Quantitative realtime PCR confirmed differential expression of select genes and non-coding RNAs within individual samples. These results demonstrate that transcriptome sequencing has the potential to provide new insights into the biology of the airway field of injury associated with smoking and lung cancer. The measurement of both coding and non-coding transcripts by RNA-seq has the potential to help elucidate mechanisms of response to tobacco smoke and to identify additional biomarkers of lung cancer risk and novel targets for chemoprevention. / 2031-01-01

Association between Smoking and Functional Outcome in Acute Ischemic Stroke Population Treated with Tissue Plasminogen Activator Iretioluwa Ajani1, Oluyemi Rotimi1, Olubunmi Kuku1, Ndukwe Kalu1, Olakunle Oni1, Nwabueze Christian1,Thomas Nathaniel2, Shimin Zheng1* 1Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614 2Department of Neurology, Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208 *Sponsoring faculty Background The effect of smoking on outcome in acute ischemic stroke patients treated with tissue plasminogen activator (TPA) is debatable. Based on the hypothesis that smokers may have more effective thrombolysis with TPA. Some clinical studies have demonstrated a favorable outcome while others have seen worse prognosis or no effect at all. This study seeks to determine the association between smoking and functional improvement in TPA treated and non-treated patients. Methods We analyzed data from the Greenville Health System (GHS) stroke registry on stroke patients between January 2010 and December 2013. Patients were divided into two groups: those treated with TPA and those not treated with TPA but presenting within 4.5 hours. Logistic regression analysis was conducted to assess if smoking was associated with improvement in ambulation. Results Of 1,446 patients, 595 (41.15 %) were treated with TPA (181 smokers (30.42%), 414 non-smokers (69.58 %) and 851 (58.85%) not treated with TPA (198 smokers (23.27 %), 653 non-smokers (76.73 %). In the multiple logistic models, smoking was not independently associated with favorable outcome in patients treated with TPA (OR = 0.84; 95% CI = 0.54 – 1.33; P = 0.46) and those not treated with TPA (OR = 0.96; 95% CI = 0.64 – 1.44; P-value = 0.85) though the bivariate models showed significant association. Conclusion There is no association between smoking and functional outcome in stroke patients regardless of TPA treatment. The effect of smoking on outcome in acute ischemic stroke patients treated with tissue plasminogen activator (TPA) is however stronger than those not treated with TPA.

The adverse interaction between smoking and chronic pain has been known for decades. A variety of chronic pain conditions – ranging from headache to low back pain to fibromyalgia – markedly exacerbate smoking prevalence and intensity in packs per day among multiple patient populations. In patients seeking pain treatment, the prevalence of smoking approaches 50%, compared to less than 20% in the general population. Perhaps not surprisingly, the relationship is bidirectional: not only does persistent pain increase rates and intensity of smoking, but smoking also appears to exacerbate both the intensity and associated impairment of chronic pain. In fact, smoking appears to place individuals at risk for developing a chronic pain condition and may also facilitate the transition from acute to chronic pain. The growing body of literature documenting these associations has led to the proposition of a positive feedback loop: individuals smoke in part to cope with their pain, but smoking actually worsens the pain. Despite the strong evidence for the existence of this adverse interaction, the mechanisms responsible for it remain poorly understood. A number of preclinical and clinical studies have documented that nicotinic acetylcholine receptor (nAChR) agonists, e.g., nicotine, have analgesic efficacy in the acute pain setting, such as that produced experimentally in the research laboratory or experienced by patients postoperatively. In contrast, the role of nAChR activation in modulating chronic pain is less well characterized. The experiments described in this thesis determine whether persistent pain diminishes the antinociceptive (analgesic) efficacy of an α4β2 nAChR agonist in the rostral ventromedial medulla (RVM), a key brainstem pain modulatory nucleus, and subsequently begin to elucidate the mechanisms by which persistent pain elicits this plasticity. The complete Freund’s adjuvant (CFA) model of chronic pain was employed to test the hypothesis that persistent inflammatory injury diminishes the antinociceptive efficacy of the selective and potent α4β2 nAChR agonist epibatidine in key brainstem pain modulatory nuclei. Paw withdrawal latency to a noxious heat stimulus was used to evaluate the anti-hyperalgesic and antinociceptive effects of epibatidine microinjected in the RVM or periaqueductal gray (PAG) of male rats. The effects of epibatidine were assessed both in uninjured animals and in animals at different times after intraplantar CFA injection. Interestingly, pretreatment with an α4β2-selective antagonist demonstrated that the antinociceptive effects of epibatidine in naïve rats were mediated by α4β2 nAChRs in the RVM but not in the PAG. While the antinociceptive effects of epibatidine in the RVM were abolished after two weeks of inflammatory pain, the anti-hyperalgesic effects remained unchanged. Surprisingly, epibatidine no longer appeared to be acting primarily at α4β2 nAChRs as early as four hours after injury. Persistent inflammation did not alter the anti-hyperalgesic or antinociceptive effects of epibatidine in the PAG. Radioligand binding studies were conducted to test the most parsimonious hypothesis that a global reduction in α4β2 nAChR number or binding affinity during persistent injury was in part responsible for the decreased efficacy of epibatidine in the RVM after intraplantar CFA. Saturation binding using [3H]-epibatidine in membrane homogenates prepared from RVM and PAG tissue revealed no differences in receptors between saline- and CFA-treated rats at any time after injury, suggesting that a whole-nucleus reduction in nAChRs could not explain the observed behavioral phenomena. To query functional changes with greater resolution, whole-cell patch clamp electrophysiology was employed to begin assessing the consequences of nAChR activation by nicotine at the level of the neuron. Initial studies performed in the locus coeruleus demonstrated that all neurons responded to nicotine with an inward current that desensitized with continued exposure to the drug. Neurons in the RVM exhibited significantly more heterogeneity in their response to nicotine: desensitizing inward currents were seen in some; sustained outward currents in others; inward currents followed by outward currents in a third population; and still others had no response to nicotine exposure. The sustained outward currents persisted in the presence of the sodium channel blocker tetrodotoxin, were not blocked by an α4β2 nAChR-selective antagonist, and appeared to be mediated by G protein-coupled receptors and potassium channels. Taken together, the present results demonstrate that persistent inflammatory injury produces adaptive changes in nicotinic signaling in the RVM such that the antinociceptive effects of epibatidine activation are abolished in a time-dependent manner. These changes cannot be attributed to a whole-nucleus reduction in α4β2 nAChRs. However, nicotinic signaling in the RVM is complex, and small alterations in the pre- or postsynaptic actions of nicotine may have significant ramifications for the overall nociceptive sensitivity of an animal. The data presented here suggest that plasticity in nicotinic signaling within the bulbospinal pain modulatory pathways may in part explain the adverse interaction between smoking and chronic pain observed in humans.