Biology subjects

Bagdas, D.

Publications and source records attributed to Bagdas, D..

3 recordsLinked to original sources

bioRxiv2026

Chronic pain exacerbates nicotine withdrawal severity in a sex-specific and dose-dependent manner

Chronic pain and nicotine use frequently co-occur, and individuals with chronic pain often experience greater difficulty quitting. Therefore, we examined nicotine withdrawal behaviors and analgesic-like effects in pain-naive and chronic pain conditions. Adult male and female rats underwent chronic constriction injury or sham surgery. After pain establishment, rats received twice-daily subcutaneous nicotine (0.3 or 0.7 mg/kg) or saline for 14 days. 24 h after the final injection, withdrawal was assessed, including physical signs and anxiety-like behavior. Depressive-like responses were evaluated at 72 h. Pain sensitivity and nicotines analgesic-like effects were assessed throughout. Chronic pain increased physical signs of withdrawal in both sexes, with greater effects in females. It also induced anxiety-like behavior in controls of both sexes. In rats with comorbid chronic pain and withdrawal, anxiety-like behavior was further enhanced in males, whereas females showed variable responses across assays, with increases or decreases depending on the test. Chronic pain induced depressive-like behavior in males but not in females. During withdrawal, depressive-like responses in males with chronic pain were not greater than those in the chronic pain alone group, while chronic nicotine exposure reduced depressive-like behavior in females. Nicotine produced acute analgesic-like effects that diminished over time in both pain-naive and chronic pain conditions, indicating tolerance. In pain-naive rats, repeated nicotine exposure induced mechanical hypersensitivity. Chronic pain intensified nicotine withdrawal severity in a nicotine concentration- and sex-dependent manner. These findings highlight the importance of considering pain status and sex when developing effective cessation strategies, particularly for individuals with comorbid chronic pain. SummaryChronic pain exacerbates nicotine withdrawal severity. Chronic nicotine exposure induces pain hypersensitivity and tolerance to analgesic effects. These effects vary by nicotine concentration and sex.

pharmacology and toxicology↗

bioRxiv2026

Effects of commercial unflavored and vanilla-flavored e-liquids on nicotine intake and withdrawal

Electronic cigarette liquids (e-liquids) often contain flavors and solvents that may influence nicotine addiction. In this study, we characterized the dose-response relationship of commercial unflavored nicotine e-liquids and investigated the impact of vanilla-flavored e-liquids on nicotine vapor self-administration (VSA) and withdrawal in rats. Male adolescent Sprague Dawley rats self-administered aerosols generated from commercial e-liquids containing 0, 3, 6, or 12 mg/ml nicotine in a propylene glycol (PG) and glycerol (G) vehicle. The vehicle (0 mg/ml nicotine) supported robust VSA, indicating the reinforcing effects of PG/G vapor. 3 mg/ml nicotine did not support VSA, while both 6 and 12 mg/ml nicotine concentrations produced significant reinforcement, with 6 mg/ml yielding the most stable responding. The 6 mg/ml concentration was selected for subsequent comparisons with vanilla-flavored e-liquids. Vanilla flavor (0 mg/ml nicotine) led to maintained VSA behavior, confirming its reinforcing effects. However, the combination of vanilla and nicotine (6 mg/ml) did not alter nicotine intake or withdrawal severity, as assessed by mecamylamine-precipitated somatic signs. Blood nicotine and cotinine levels were similar between nicotine and vanilla + nicotine conditions, indicating that vanilla flavor did not affect systemic nicotine metabolism. Additionally, the PG/G vehicle induced significant somatic signs, suggesting that vapor exposure itself, independent of nicotine, contributes to these physiological responses. These findings provide critical insights into the reinforcing and physiological effects of both nicotine and non-nicotine constituents in e-cigarette aerosols, underscoring the need for future studies and regulatory strategies that consider the abuse liability of flavors and solvents, such as PG/G, particularly among adolescents. Significance StatementFlavored electronic nicotine delivery systems raise concern for promoting nicotine use in youth. Using a rat vapor self-administration model, we show nicotine produces concentration-dependent reinforcement, while vanilla flavor is reinforcing but does not enhance nicotine intake or withdrawal.

pharmacology and toxicology↗

bioRxiv2018

C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception

Sensitivity to different pain modalities has a genetic basis that remains largely unknown. Employing closely related inbred mouse substrains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on nociceptive phenotypes and observed an increase in formalin-induced inflammatory nociceptive behaviors and paw diameter in B6J versus B6N mice (Charles River Laboratories). No strain differences were observed in mechanical or thermal hypersensitivity or in edema following the Complete Freunds Adjuvant (CFA) model of inflammatory pain, indicating specificity in the inflammatory nociceptive stimulus. In the chronic nerve constriction injury (CCI), a model of neuropathic pain, no strain differences were observed in baseline mechanical threshold or in mechanical hypersensitivity up to one month post-CCI. We replicated the enhanced thermal nociception in the 52.5{degrees}C hot plate test in B6J versus B6N mice from The Jackson Laboratory. Using a B6J x B6N-F2 cross (N=164), we mapped a major quantitative trait locus (QTL) underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (LOD=3.81, p<0.01; 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression QTLs (eQTLs) associated with the peak nociceptive marker that are implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (FDR < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across pain modalities.

genetics↗