*Article* **Association of Self-Rated Pain with Clinical Peri-Implant Parameters and Cytokine Profile in Smokers and Never Smokers with and without Peri-Implantitis**

**Faris A. Alshahrani 1, Firas K. Alqarawi 1, Montaser N. Alqutub 2, Abdulrahman M. AlMubarak 2, Eman M. AlHamdan 3, Samar Al-Saleh 3, Paras Ahmad 4, Fahim Vohra 3,5 and Tariq Abduljabbar 3,5,\***


**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 [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-α, MMP-1, and IL-8 were measured. The mean SPP score in group-1, group-2, and the control group was 1.3 ± 1, 3.4 ± 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-α, 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-α, 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.

**Keywords:** cigarette smoking; cytokines; pain; peri-implantitis; peri-implant crevicular fluid; inflammation
