This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in proinflammatory cytokine (TNF and TGFB1) and chemokine (CXCL8) genes with painful temporomandibular disorders (TMDp) (Figure 1). Diagnosis of TMDp involves myalgia and/or arthralgia. The study included 170 individuals: 85 with diagnosed TMDp and 85 healthy controls (CTR). In the TMDp group, the average age was 29.96, with 76 females (89.41%) and 9 males (10.59%). In the control group, the average age was 26.23, with 62 females (72.88%) and 23 males (27.12%). Intensity of orofacial pain was measured through Characteristic Pain Intensity (CPI) score from Graded Chronic Pain Scale, whereas TMD patients with CPI>50 were considered as a high pain intensity group (HPI). Genomic DNA was extracted from buccal mucosa swabs (Figure 2). Single nucleotide polymorphisms (SNPs) in genes encoding interleukin 8 (CXCL8; rs2227306, rs2227307), transforming growth factor β (TGFB1, rs4803455) and tumour necrosis factor-alpha (TNF, rs1800629) were analysed by real time-PCR using Taqman Genotyping assays (Figure 3). The assessment was performed according to dominant and recessive genetic models where minor allele represented the risk allele. Chi-Square Test, Fisher's Exact Test and Mann-Whitney U test were used for data analysis. The frequency of patients carrying minor allele G of rs2227307 was higher in TMDp patients than in CTRs (70% vs. 55%, p=0.041) (Figure 4). Carriers of minor allele G and T of rs2227307 and rs2227306 respectively were significantly more represented in HPI group when compared to the rest of the participants (75% vs. 57%, p=0.023; 71% vs. 55%, p=0.047, respectively) (Figure 5,6). Also, TMDp subjects carrying GG+GT of rs2227307 polymorphism reported significantly shorter pain duration in last 6 months (80 vs.112 days, p=0.041) and significantly higher worst facial pain (7.3 vs. 6.5, p=0.031) compared to the subjects with the TT genotype. Certain SNPs may predict pain intensity and chronicity in TMDp patients. Our results support the association between SNPs in pro-inflammatory chemokine genes (CXCL8) and TMDp, highlighting the potential utility of genetic testing in predicting pain severity. Further research is needed to confirm these findings and explore underlying mechanisms.