## 4 Discussion  
It is postulated that SPP, peri-implant clinical, and radiographic parameters are worse among cigarette smokers with peri-implantitis than never smokers without peri-implantitis. In this study, the clinic-radiographic peri-implant parameters were poorer among cigarette smokers with peri-implantitis than never smokers without peri-implantitis; no statistically significant correlation was observed between SPP and expression of TNF-\(\alpha\), MMP-1, and IL-8. However, several variables might have altered the findings, therefore, these results should be interpreted with extreme caution. A unique ecological niche is formed by the gingival sulcus for bacterial colonization. The bacterial biofilm in the gingival sulcus promotes inflammation in the surrounding connective tissues [32]. An inflammatory process is triggered by the imbalance between host response and microbial challenge at the implant-soft tissue interface [33]. Cytokines, including IL-6, IL-1B, TNF-a, are released from the cells of neutrophils, macrophages, connective tissue fibroblasts, dendritic cells, and gingival epithelium. Moreover, a number of enzymes, including aspartate aminotransferase, alkaline phosphatase, and MMPs, are formed by osteoclasts, fibroblasts, and neutrophils, resulting in the degradation of connective tissue collagen and alveolar bone [34; 35]. Over 90 different molecular components in gingival circular fluid have been assessed for potential periodontal disease diagnosis linked with the natural dentition [36]. However, considerably fewer PICF components have been investigated around dental implants. In the current study, certain disparities were also observed. For example, clinical peri-implant examination revealed that PI and BOP were significantly raised in never smokers with peri-implantitis than smokers with peri-implantitis and the control group. Moreover, in cigarette smokers, BOP is masked as nicotine causes the vasoconstriction of gingival blood vessels [37]. From a clinical perspective, the findings of this study conform \begin{table}
\begin{tabular}{c c c c} \hline \hline
**SPP Score** & **OR** & **95\% CI** & **\(p\)-Value** \\ \hline
**TNF-\(\alpha\)** & & & \\ \hline
1 & 0.45 & 0.32–0.58 & \\
2 & 0.13 & 0.09–0.17 & \\
3 & 0.72 & 0.62–0.82 & \\
4 & 0.32 & 0.15–0.49 & \\
5 & 0.28 & 0.22–0.34 & \\
6 & 0.16 & 0.10–0.22 & \\ \hline
**MMP-1** & & & \\ \hline
1 & 0.15 & 0.05–0.25 & \\
2 & 0.36 & 0.31–0.41 & \\
3 & 0.52 & 0.43–0.61 & \\
4 & 0.23 & 0.15–0.46 & \\
5 & 0.19 & 0.11–0.27 & \\
6 & 0.08 & 0.05–0.11 & \\ \hline
**IL-8** & & & \\ \hline
1 & 0.16 & 0.12–0.21 & \\
2 & 0.47 & 0.40–0.54 & \\
3 & 0.39 & 0.21–0.57 & \\
4 & 0.61 & 0.56–0.66 & 0.008 \\
5 & 0.07 & 0.06–0.08 & \\
6 & 0.26 & 0.18–0.34 & \\ \hline \hline \end{tabular} Abbreviations: CI = confidence interval; IL-8 = interleukin-8; MMP-1 = matrix metalloproteinase-1; OR = odds ratio; PICF = peri-implant vesicular fluid; SPP = self-perceived pain; TNF-\(\alpha\) = tumor necrosis factor-alpha.  
\end{table} 
Table 4: Statistical comparisons of the SPP score with PICF cytokines levels. to the proposed hypothesis as scores of peri-implant PD are significantly elevated among cigarette smokers than never smokers. One explanation for this finding is that cell death and formation of matrix metalloproteinases are induced and enhanced by cigarette smoke extracts, respectively, leading to the deterioration of the extracellular matrix proteins such as collagen [38]. Furthermore, the expression for RAGE is increased four times by nicotine in human gingival cells [39]; an increased AGE/RAGE interaction aggravates periodontal tissue inflammation [39]. In the current study, smokers and never smokers with peri-implantitis did not show a significant difference in CBL. Among all three groups, the subjects had a mean age between 38 and 42 years. It is well-established that advancing or increasing age is a predisposing factor for the increased loss of alveolar bone around dental implants and natural dentition [14]. In one study, [PERSON] et al.