Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients' physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence-induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.
Animals ; Humans ; Nicotine/adverse effects* ; Pain ; Pain Threshold ; Smoking Cessation ; Tobacco Use Disorder

In this study, two proposed scales of nicotine dependence were compared: self-administered nicotine intake and acute heart rate sensitivity to smoking. Our aim was to determine if these nicotine dependence scales would rank relative dependence the same in a sample of 15 male chronic smokers who smoked their first cigarette in the morning after overnight abstinence. Heart rate and plasma nicotine levels were measured before and 5, 10, 15, and 30 min after smoking. The results of this pilot study suggest that heart rate sensitivity and nicotine intake do not have a direct linear relationship, but rather a curvilinear relationship. A marked increase in heart rate sensitivity was observed at approximately the 70th percentile of nicotine intake.
Heart Rate ; Humans ; Male ; Nicotine ; administration & dosage ; Pilot Projects ; Sensitivity and Specificity ; Smoking ; adverse effects ; Tobacco Use Disorder ; physiopathology

OBJECTIVETo observe the role of magnesium sulfate in vascular calcification, to explore the role and the mechanism of magnesium sulfate in vascular calcification.

METHODSThe vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN) in SD rats. To estimate the extent of calcification by Von Kossa staining, calcium content and alkaline phosphatase activity, osteopontin (OPN) mRNA were determined by using semi-quantitative reverse-transcription polymerase chain reaction.The malondialdehyde (MDA) and nitric oxide (NO) content and activities of superoxide dismutase(SOD) were measured by biochemistry.

RESULTSA strong positive staining of black/brown areas among the elastic fibers of the medial layer in calcified aorta by Von Kossa staining, calcium content and ALP activity in calcified arteries increased by 3.9-and 3.4-fold as compared with the controls. The expression of OPN mRNA was up-regulated by 40% (P < 0.01). The lipid peroxidation products MDA in vascular were increased 2.0-fold (P < 0.01). The NO content and SOD activity were greatly decreased by 64% and 72% (P < 0.01), respectively, compared with controls. However, calcium content and ALP activity in VDN plus magnesium sulfate group were lower than those in VDN group. Low and high dosage magnesium sulfate obviously relieved degree of calcification in the cardiovascular tissues in a dosage-dependent manner (P < 0.01).

CONCLUSIONMagnesium sulfate plays a role in the pathogenesis of vascular calcification by reducing vascular calcification and decreasing vascular injury.

Animals ; Cholecalciferol ; adverse effects ; Magnesium ; pharmacology ; Male ; Nicotine ; adverse effects ; Osteopontin ; metabolism ; RNA, Messenger ; genetics ; Rats ; Vascular Calcification ; chemically induced ; pathology

OBJECTIVETo review the current evidence that links smoking to obstructive sleep apnea (OSA) and to discuss some potential mechanisms proposed for these links.

DATA SOURCESWe searched PubMed and Medline to identify studies investigating the interaction between smoking and OSA.

STUDY SELECTIONArticles regarding the relationship between smoking and OSA were selected. Studies considered smoking as a confounding factor were excluded.

RESULTSThe association of smoking and OSA has been confirmed in several studies. The effects of smoking on the pathophysiology of OSA may include smoking-induced upper airway inflammation, stimulant effects of nicotine on upper airway muscles, and a "rebound effect" due to nightly short-term nicotine withdrawal, or all of the above. In addition, the coexistence of OSA and smoking may have more widespread implications for cardiovascular dysfunction in patients with OSA. Finally, OSA might be responsible for the addiction to nicotine.

CONCLUSIONSSmoking may act as a risk factor for OSA and join with OSA in a common pathway to increase the risk of systematic injury. OSA, in turn, may be a predisposing factor for smoking. Thus, smoking cessation is recommended when considering treatment for OSA, and treating OSA may be a necessary precondition for successful smoking cessation.

Asthma ; epidemiology ; etiology ; Bronchi ; drug effects ; Humans ; Nicotine ; pharmacology ; Risk Factors ; Sleep ; physiology ; Sleep Apnea, Obstructive ; epidemiology ; etiology ; Smoking ; adverse effects ; Tobacco Use Disorder ; epidemiology ; etiology

OBJECTIVETo evaluate the impact of nicotine- and tar-free cigarette smoke extract (fCSE) on the serum testosterone (T) level and erectile function of male rats.

METHODSWe randomized 30 male SD rats to three groups of equal number to receive subcutaneous injection of PBS (1.0 ml / 300 g body weight per day), fCSE (1.0 ml/300 g body weight per day), and reduced glutathione hormone (GSH, 200 mg per kg body weight per day) in addition to fCSE (fCSE + GSH), respectively, all for 8 weeks. Then we evaluated the erectile function of the rats by measuring the maximal intracavernous pressure (MICP), mean arterial pressure (MAP), ICP/MAP ratio, time of stimulation to MICP (Tmax), and cavernosal filling fate (CFR). We determined the serum T level, the activities of superoxide dismutase (SOD) , malondialdehyde (MDA), and nitric oxide synthase (NOS) in the cavernosal tissue, and also observed the morphological changes of the corpus cavernosum.

RESULTSCompared with the controls, the rats of the fCSE group showed obvious decreases in the levels of serum T ([5.37 ± 1.43] vs [3.22 ± 1.11] μg/L), NOS ([2.90 ± 0.27] vs [1.67 ± 0.18] U/mg) , and SOD ([18.41 ± 1.09] vs [13.36 ± 1.18] U/mg prot) and erectile function-related indexes MICP ([85.92 ± 6.36] vs [58.99 ± 10.76] mmHg), MICP/MAP (0.86 ± 0.09 vs [0.56 ± 0.08]), and CFR (2.14 ± 0.44 vs 0.89 ± 0.44), but markedly increased Tmax ([29.90 ± 5.78] vs [42.90 ± 8.56]s), with a positive correlation between the serum T level and CFR (r = 0. 364, P < 0.05). Masson staining revealed a lower ratio of the corpus cavernosum smooth muscle tissue to collagen fiber in the fCSE group (0.27 ± 0.04) than in the control (0.98 ± 0.12). Compared with the fCSE group, the fCSE + GSH group exhibited significantly improved MICP ([58.99 ± 10.76 ] vs [77.95 ± 7.71] mmHg), MICP/MAP (0.56 ± 0.08 vs 0.77 ± 0.09), and CFR (0.89 ± 0.44] vs 1.76 ± 0.42) and shortened Tmax ([42.90 ± 8.56 ] vs [32.10 ± 5.84 ] s). The ratio of the corpus cavernosum smooth muscle tissue to collagen fiber was higher in the fCSE + GSH than in the fCSE group (0.77 ± 0.09 vs 0.27 ± 0.04) but still lower than in the control (0.98 ± 0.12).

CONCLUSIONNicotine- and tar-free cigarette smoke extract reduces the serum T level and erectile function of rats, which is related to oxidative stress. Antioxidant therapy can improve erectile function but has a limited value for morphological protection of the penile tissue.

Animals ; Erectile Dysfunction ; chemically induced ; Male ; Malondialdehyde ; metabolism ; Muscle, Smooth ; pathology ; Nicotine ; Nitric Oxide Synthase ; metabolism ; Penile Erection ; drug effects ; Penis ; pathology ; Rats ; Rats, Sprague-Dawley ; Smoke ; adverse effects ; Superoxide Dismutase ; metabolism ; Tars ; Tobacco ; adverse effects

This study investigated sociodemographic and smoking behavioral factors associated with smoking cessation according to follow-up periods. In this randomized, double-blind, placebo-controlled trial of transdermal nicotine patches, subjects were a total of 118 adult male smokers, who were followed up for 12 months. Univariable logistic regression analysis and stepwise multiple logistic regression analyses were performed to identify the predictors of smoking cessation. The overall self-reported point prevalence rates of abstinence were 20% (24/118) at 12 months follow-up, and there was no significant difference in abstinence rates between placebo and nicotine patch groups. In the univariable logistic regression analysis, predictors of successful smoking cessation were the low consumption of cigarettes per day and the low Fagerstrom Test for Nicotine Dependence (FTND) scores (p<0.05) at 3, 6, and 12 months follow-up. In the stepwise multiple logistic regression analyses, predictors of successful smoking cessation, which were different according to the follow- up periods, were found to be the low consumption of cigarettes per day at the short-term and midterm follow-up (< or =6 months), older age, and the low consumption of cigarettes per day at the long-term follow-up (12 months).
Administration, Cutaneous ; Adult ; Age Factors ; Double-Blind Method ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Nicotine/*administration & dosage/adverse effects ; Smoking/*psychology ; *Smoking Cessation

OBJECTIVETo observe the effects of nicotine on endogenous carbon monoxide (CO) concentration and nitric oxide synthase (NOS) activity in the corpus cavernosum of adult male rats, and explore the possible mechanism of cigarette smoking affecting erectile dysfunction.

METHODSForty adult male rats were equally divided into three treatment groups to receive subcutaneous injection of nicotine at 0.5 mg/kg pre d for 1, 2 and 3 months, and a control group to receive saline only. After treatment, the corpus cavernosum was harvested for detection of CO concentration by modified two-wavelength spectrophotometry and NOS activity by improved Griess measurement.

RESULTSCO concentration and NOS activity were decreased by 9.05 and 13.37%, respectively, after 1 month of nicotine injection (P < 0.01), 16.47 and 22.5% after 2 months (P < 0.01), and 22.99 and 31.74% after 3 months (P < 0.01), as compared with (13.664 +/- 0.404) umol/mg prot and (9.721 +/- 0.470) U/mg prot in the control group.

CONCLUSIONNicotine can reduce endogenous CO concentration and NOS activity in the corpus cavernosum of adult male rats, which suggests the involvement of endogenous CO and NOS in the pathophysiological process of smoking-induced erectile dysfunction .

Animals ; Carbon Monoxide ; metabolism ; Erectile Dysfunction ; chemically induced ; Male ; Nicotine ; toxicity ; Nitric Oxide Synthase ; metabolism ; Penis ; metabolism ; Rats ; Smoking ; adverse effects

In recent years, the quality of human sperm and its fertility potential have decreased dramatically. This may suggest that the quality of semen has deteriorated partly due to the effects of increasing toxic factors in the environment. Infertility remains a major problem in society, and recent data show that as many as one in four couples is trying to solve the problem. Male infertility accounts for 40% of infertility cases. Many environmental agents such as tobacco smoke and nicotine and genetic factors have been implicated in the poor sperm function and resultant infertility. The article is a review of the impacts of nicotine on human fertility potential. According to our results, nicotine is proved to be a potent pro-oxidant to the biological samples like spermatozoa population and is able to alter the fertility potential of man by inducing the membrane impairments, altering the GSH metabolism cycle, changing the sperm morphology and motility, and also inducing the DNA fragmentation. Antioxidant supplementation could reverse partially the negative effect of nicotine on sperm functions. However, further studies are necessary to illuminate the other dark sides of nicotinic infertility in human spermatozoa.
DNA Damage ; Dose-Response Relationship, Drug ; Fertility ; drug effects ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Humans ; Infertility, Male ; chemically induced ; Lipid Peroxidation ; drug effects ; Male ; Nicotine ; adverse effects ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; metabolism

Cigarette smoking is the most important preventable cause of death in Korea. Smoking should be considered as a chronic disease attributed to nicotine dependence which needs a long term care. Nicotine dependence and withdrawal symptoms are major barriers to smoking cessation and can be successfully managed by pharmacotherapy. There are two types of pharmacotherapy for nicotine dependence, nicotine-replacement therapy(NRT) and nonnicotine-replacement therapy. Nicotine, which can be administered by patch, gum, inhaler, and nasal spray, doubled the smoking cessation rate. NRTs are usually well tolerated. Sustained-release bupropion, an antidepressant, doubled the smoking cessation rate when combined with counselling. Bupropion can induce seizure in less than 0.1% by lowering the seizure threshold. Nortriptyline and clonidine can be used as second line drugs for smoking cessation. They are similar in efficacy compared to NRT or bupropion but they frequently have adverse drug reactions. Combination of bupropion with NRT is more efficacious than NRT alone but not more effective than bupropion alone. There is no convincing evidence to recommend a specific drug for smoking cessation in women. NRT and bupropion can be useful in special situations for adolescent smokers, but evidence is not enough to recommend pharmacotherapy for adolescent smokers. Weight gain is the main barrier to smoking cessation, especially in women. Vigorous exercise reduced weight gain. Nicotine gum, bupropion also temporarily reduced weight gain after smoking cessation, but only while the drug was being administered. As there are sound evidences for the effect of pharmacotherapy in smoking cessation, it is necessary for physicians to integrate it into their daily practices.
Adolescent ; Bupropion ; Cause of Death ; Chronic Disease ; Clonidine ; Drug Therapy* ; Drug-Related Side Effects and Adverse Reactions ; Female ; Gingiva ; Humans ; Korea ; Long-Term Care ; Nebulizers and Vaporizers ; Nicotine* ; Nortriptyline ; Seizures ; Smoke ; Smoking ; Smoking Cessation ; Substance Withdrawal Syndrome ; Tobacco Use Disorder* ; Weight Gain

OBJECTIVETo investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro.

METHODMouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured.

RESULTSCSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5 mumol/L Ca2+, but promoted swelling response at 250 mumol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved.

CONCLUSIONThe toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.

Adenosine Triphosphatases ; pharmacology ; Animals ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; Brain ; pathology ; Electron Transport Complex IV ; pharmacology ; Free Radicals ; Ganglionic Stimulants ; toxicity ; Mice ; Mitochondria ; pathology ; Nicotine ; toxicity ; Smoke ; adverse effects ; Tobacco