Time-course of pain and salivary opiorphin release in response to oral capsaicin differ in burning mouth syndrome patients, temporomandibular disorders patients and control subjects.

OBJECTIVES: Opiorphin is an analgesic peptide released by salivary glands and capsaicin an agonist of TRPV1 receptors eliciting burning sensations. The primary objective of this study was to assess opiorphin release after stimulation of the tongue by capsaicin (STC). The secondary objectives were to compare opiorphin release after STC in 3 groups of subjects [healthy (CTRL), Burning Mouth Syndrome (BMS), painful Temporomandibular disorders (TMDp)] and pain evoked by STC in these 3 groups. MATERIALS AND METHODS: Salivary opiorphin was assessed with high-performance liquid chromatography at 3 different time points (baseline, after 5 min and 20 min of STC). Pain was self-reported on a (0-10) numeric rating scale. RESULTS: Three groups (N = 16) of adults were recruited at the Clinical Hospital Centre and School of Dental Medicine in Zagreb. Opiorphin levels were higher (1) in TMDp compared to CTRL in 1st (2.23 ± 1.72 pg/ul vs. 0.67 ± 0.44 pg/ul, p = 0.002) and 3rd sampling (2.44 ± 2.01 pg/ul vs. 0.74 ± 0.52 pg/ul, p = 0.020) and (2) within BMS group at 3rd sampling vs. baseline (p < 0.025). Pain scores were higher in BMS compared to TMDp (p < 0.025) and CTRL (p < 0.025). CONCLUSION: This study evidenced (1) a differential basal amount of opiorphin in two pain conditions and control subjects (2) a differential kinetic of release of opiorphin after STC in CTRL, BMS and TMDp (3) a differential pain perception after STC in BMS and TMDp vs. CTRL, which can provide a readout for animal models. CLINICAL RELEVANCE: The specific regulation of opiorphin release in patients with orofacial painful conditions provides valuable insights for clinicians and researchers in physiology and pathology and encourages further research in this area. TRIAL REGISTRATION: ClinicalTrials.gov NCT04694274. Registered on 01/05/2021.

Genetic influence on treatment outcomes in patients with pain-related temporomandibular disorders.

BACKGROUND: Single nucleotide polymorphisms (SNPs) may influence pain susceptibility and impact treatment response in pain-related temporomandibular disorders (TMDp). OBJECTIVE: Explore the role of COMT (rs4646310, rs6269, rs4818, rs4680) and OPRM1 (rs1799971) genotypes in regulating treatment response. METHODS: Sixty TMDp patients (55 females and 5 males), diagnosed with the Diagnostic Criteria for TMD (DC/TMD), underwent standardised treatment (information and education, home physical therapy, occlusal splint) for 6 months. Treatment outcomes included: pain intensity, pain-free mouth opening, jaw functional limitation, depression, and anxiety. Genotyping for COMT and OPRM1 SNPs was performed using DNA from buccal mucosa swabs and TaqMan assays. Statistical analysis was carried out to compare the changes in treatment outcomes and the influence of genotypes on treatment response. RESULTS: Significantly less pain reduction was observed in minor allele carriers of rs4646310, and rs4680 compared to dominant homozygous (p < .025). Minor allele carriers of rs1799971 and rs4646310 demonstrated worsening in pain-free mouth opening while dominant homozygous exhibited improvement (p < .025). Significantly less anxiety reduction was observed in minor allele carriers of rs4646310 compared to dominant homozygous (p = .003). Of the all variables assessed in the regression model, carrying a minor allele of rs1799971 predicted a poorer treatment response considering pain-free mouth opening while carrying a minor allele of rs4646310 predicted less pain and less anxiety reduction. CONCLUSION: Our findings indicate that certain SNP variants of the COMT and OPRM1 genes were associated with poorer treatment response and may therefore play a significant role in the classification of TMDp patients. Also, assessment of patient genotype could potentially aid in predicting treatment response.