###### Abstract  
To examine the association between self-perceived pain (SPP), clinical and radiographic peri-implant parameters, and biomarker levels among smokers and never smokers with and without peri-implantitis. Sixty individuals (20 smokers with peri-implantitis [group-1], 20 never smokers with peri-implantitis [group-2] and 20 never smokers without peri-implantitis [group-2] and 20 never smokers without peri-implantitis [control-group]) were included. SPP was evaluated using a numeric pain rating scale (NPRS). Peri-implant plaque index (PI), probing depth (PD), and bleeding on probing (BOP) were recorded. After obtaining the samples, the levels of TNF-\(\alpha\), MMP-1, and IL-8 were measured. The mean SPP score in group-1, group-2, and the control group was 1.3 \(\pm\) 1, 3.4 \(\pm\) 1, and zero, respectively. The peri-implant mean PD (\(p<0.05\)), BOP (\(p<0.05\)), PI (\(p<0.05\)), and crestal bone loss (CBL) (\(p<0.05\)) were significantly higher among test groups than the control group. The levels of TNF-\(\alpha\), MMP-1, and IL-8 were significantly raised among group-1 and group-2 than the control group. A significant correlation between increasing SPP and PICF TNF-\(\alpha\), MMP-1, and IL-8 levels was observed based on regression analysis. Proinflammatory biomarkers were higher in smokers with peri-implantitis than never smokers with and without peri-implantitis, with a significant association between the proinflammatory cytokines and SPP. c 2021 26 May 2021 26 May 2021 26 May 2021 26 June 2021  
The abutment screw loosening or failure is a rare, but very unpleasant failure. Several studies have reported that, after dental implant osseointegration, abutment screw loosening seems to be the most frequent issue linked with implants [8; 9; 10; 11]. Many factors contribute to the etiology of these technical failures, such as fabrication failures, non-passive fit of the suprastructures, improper placement technique, fatigue, excessive occlusal load, and the utilization of unfavorable components including copy products [12]. A few reports suggest that most of the failures are related to the suprastructure rather than to the dental implants themselves [13]. Cigarette smoking is a well-established predisposing factor for both peri-implant and periodontal soft tissue inflammation; [14] and CBL surrounding dental implants and natural teeth [15]. One justification in this aspect might be that the generation and deposition of advanced glycation end products (AGEs) in the periodontal tissues is increased by cigarette smoking [16]. The linkage of AGEs with their receptors (RAGE), inflammatory cytokines including matrix metalloproteinase (MMP)-1, interleukin (IL)-8, and tumor necrosis factor-alpha (TNF-\(\alpha\)) are generated by human gingival fibroblasts that stimulate inflammation [17]. Furthermore, collagen degradation is increased by cigarette smoking via influencing tissue inhibitors of metalloproteinases [18]. Moreover, the RAGE's expression in the gingival tissues is upregulated; the production of reactive oxygen species (ROS) is stimulated by metabolites of nicotine, i.e., normicotine which damages the periodontal tissues. Besides contributing to delayed periodontal wound healing, these variables might also compromise peri-implant tissue healing. The destructive inflammatory cytokines cause deteriorating clinical peri-implant parameters including plaque index (PI), PD, gingival index (GI), elevated CBL on the distal and mesial aspects of the dental implant. If untreated, implant failure may be caused [19]. [PERSON] et al. [20] evaluated the clinical peri-implant parameters and levels of cotinine in peri-implant crevicular fluid (PICF) of thirty-five never-smokers and thirty-five tobacco smokers. The findings reported that cotinine levels and peri-implantitis in the PICF were considerably lower in never smokers as compared to tobacco smokers.