Mild systemic inflammation enhances response to OnabotulinumtoxinA in chronic migraineurs.

The anti-inflammatory effect of OnabotulinumtoxinA (OnabotA) has been a matter of discussion for many years. In chronic migraine, however, increased pro-inflammatory state is associated with good response to OnabotA. We aimed to investigate whether a mild systemic inflammatory state elicited by a common oral infection (periodontitis) could enhance treatment response to OnabotA. In this study, we included 61 chronic migraineurs otherwise healthy treated with OnabotA of which 7 were poor responders and 54 good responders. Before receiving OnabotA therapy, all participants underwent a full-mouth periodontal examination and blood samples were collected to determine serum levels of calcitonin gene-related peptide (CGRP), interleukin 6 (IL-6), IL-10 and high sensitivity C-reactive protein (hs-CRP). Periodontitis was present in 70.4% of responders and 28.6% of non-responders (P = 0.042). Responders showed greater levels of inflammation than non-responders (IL-6: 15.3 ± 8.7 vs. 9.2 ± 4.7 ng/mL, P = 0.016; CGRP: 18.8 ± 7.6 vs. 13.0 ± 3.1 pg/mL, P = 0.002; and hs-CRP: 3.9 ± 6.6 vs. 0.9 ± 0.8 mg/L, P = 0.003). A linear positive correlation was found between the amount of periodontal tissue inflamed in the oral cavity and markers of inflammation (IL-6: r = 0.270, P = 0.035; CGRP: r = 0.325, P = 0.011; and hs-CRP: r = 0.370, P = 0.003). This report shows that in presence of elevated systemic inflammatory markers related to periodontitis, OnabotA seems to reduce migraine attacks. The changes of scheduled inflammatory parameters after treatment and subsequent assessment during an adequate period still need to be done.

Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs.

OBJECTIVES: Periodontitis (PD) and chronic migraine (CM) have been recently linked, and inflammatory processes and vascular endothelial changes are hypothesized as potential mediators of this relationship. The aim of this cross-sectional analysis was to investigate the potential association of PD with vascular systemic inflammation and complement activation in patients with CM. MATERIALS AND METHODS: Ninety-four chronic migraineurs underwent a full-mouth periodontal evaluation and a measure of PD activity and severity, namely the periodontal inflamed surface area (PISA) was calculated for each patient. We divided CM patients according to their periodontal status: mild PD (N = 14), moderate PD (N = 22), severe PD (N = 19), and non-PD (N = 39). Serum levels of C-reactive protein (CRP), pentraxin 3 (PTX3), soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), and complements C3 and C4 were measured outside of migraine attacks. RESULTS: We found that severe periodontal patients had significantly higher circulating levels of PTX3 and sTWEAK compared with those without PD (2475.3 ± 1646.8 pg/mL vs. 516.6 ± 1193.8 pg/mL, P < 0.0001 and 672.4 ± 118.2 pg/mL vs. 485.7 ± 112.2 pg/mL, P < 0.0001; respectively). For the remaining biomarkers, no significant differences were found between groups. Severe PD was independently associated with higher levels of PTX3 (ß = 1997.6, P < 0.0001) and sTWEAK (ß = 187.1, P < 0.0001) but not with CRP, C3, and C4. PISA positively correlated to PTX3 (r = 0.475, P < 0.0001) and sTWEAK (r = 0.386, P < 0.0001). CONCLUSIONS: Based on these preliminary results, severe PD was linked with vascular systemic inflammation in patients with CM. However, further longitudinal studies should be performed to confirm these findings. CLINICAL RELEVANCE: sTWEAK and PTX3 measured in serum could be used as biomarkers in the PD-CM link.

Periodontal inflammation is related to increased serum calcitonin gene-related peptide levels in patients with chronic migraine.

BACKGROUND: Recently, a relationship was found between periodontitis and chronic migraine. Calcitonin gene-related peptide (CGRP) is a key element in migraine pathophysiology. However, no information exists of the potential association between periodontal inflammation and CGRP in chronic migraine. The aim of the study was, therefore, to investigate whether there is a link between periodontitis and peripheral levels of CGRP in a cohort of patients with chronic migraine. METHODS: We included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Sociodemographic data and comorbidities were assessed by means of a standard questionnaire. We collected blood samples and serum concentrations were done for CGRP, interleukin (IL)-6 and IL-10. RESULTS: In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP (19.7 ± 6.5 versus 15.3 ± 6.2 pg/mL, P < 0.0001) and IL-6 (15.1 ± 9.2 versus 9.6 ± 6.3 pg/mL, P < 0.0001) while non-significant differences were observed with IL-10 (2.0 ± 1.0 versus 2.8 ± 1.5 pg/mL, P = 0.675) concentrations than those without periodontitis. PISA was independently associated with CGRP in patients with chronic migraine (ß = 0.003; 95% confidence interval: 0.001 to 0.006, P = 0.031). PISA correlated positively with CGRP (r = 0.236; P = 0.017) and IL-6 (r = 0.262; P = 0.008) in chronic migraine. CONCLUSIONS: Periodontal inflammation is associated with increased circulating levels of CGRP in chronic migraineurs. Elucidating the exact mechanisms through which periodontitis and CGRP are linked in these patients deserves further investigation.

Association between periodontitis and chronic migraine: a case-control study.

The aim of this investigation was to examine whether chronic periodontitis (CP) is a risk indicator of chronic migraine (CM). We performed a case-control study consisted of 102 cases (patients diagnosed with CM) and 91 controls (non-CM individuals) matched by age and gender. Full-mouth periodontal charts, demographic, medical, clinical, as well as neurological data were obtained. In addition, high sensitive C-reactive protein serum levels were determined from blood samples of both cases (taken during migraine interictal period) and controls. The prevalence of CP was significantly higher in patients with CM compared to those without CM (58.8 vs. 30.8%, p < 0.0001). Logistic regression analysis showed that CP was significantly associated with the presence of CM, independently of well-known chronifying factors of migraine (OR 2.4; 95% CI 1.2-4.7; p = 0.012). Based on our results, CP could be considered as a risk indicator of CM. However, more evidence is necessary to investigate if this relationship is causal or not.

High serum procalcitonin levels in patients with periodontitis and chronic migraine.

BACKGROUND: To evaluate the contribution of chronic periodontitis (CP) to serum procalcitonin (proCT) levels in chronic migraine (CM) patients in a cross-sectional study. METHODS: We included 138 subjects divided into 4 groups based on clinical features of CM and periodontal parameters: systemically and periodontally healthy individuals (n = 37), systemically healthy and CP patients (n = 19), CM and periodontally healthy patients (n = 34), and CM+CP patients (n = 48). Demographic, neurological, clinical data as well as full-mouth periodontal records were obtained. ProCT and high sensitive C-reactive protein (hs-CRP) serum levels were determined from blood samples taken during migraine interictal period. RESULTS: Patients from the CP+CM group (0.056±0.006 ng/mL) had significantly higher serum proCT levels in comparison with the systemically and periodontally healthy group (0.029±0.019 ng/mL), CM group (0.041±0.002 ng/mL), or CP group (0.034±0.014 ng/mL) (p < 0.001). There were no significant differences in hs-CRP between groups (p = 0.081). Multiple linear regression analysis showed that CP was associated with increased proCT levels in CM patients (R2  = 0.293, p < 0.001). CONCLUSIONS: CP independently contributes to elevated serum proCT levels in CM patients. These findings suggest that CP could play a role in migraine chronification.

The role of leptin as a biomarker in the relationship between periodontitis and chronic migraine.

AIM: To evaluate the prevalence of periodontitis (CP) and its contribution to serum leptin levels in chronic migraine (CM). MATERIAL AND METHODS: In this case-control study, we included 150 subjects divided into healthy controls (n = 58) and CM patients (n = 92). Demographic, neurological, clinical data as well as full-mouth periodontal records were obtained. Serum leptin levels were measured by ELISA technique. RESULTS: Both the prevalence of CP and mean serum leptin levels were significantly higher in patients with CM in comparison with controls (57.6% versus 36.2%, p = .01 and 16.4 versus 7.2 ng/ml, p < .0001, respectively). Patients from the CM group who had CP showed significantly higher leptin concentrations than CM patients without CP (19.8 versus 11.8 ng/ml, p < .0001). Multivariable linear regression analysis showed that CP was an independent contributor to raised leptin levels in CM patients (R2  = 0.270, p = 0.013). CONCLUSIONS: CP is prevalent in CM patients and when present it contributes to elevated serum leptin levels, independently of other confounding factors. Therefore, it seems that CP via leptin could be involved in the process of migraine chronification.

Periodontal disease as a potential factor of migraine chronification.

Migraine is a hereditary constitutional base disorder, which is characterized by recurrent episodes of headache pulsatile characteristics associated with photophobia/phonophobia, nausea and/or vomiting. The main complication in migraine is the chronicity of the process, now recognized as a chronic migraine. Although pathogenic mechanisms that may influence the pathophysiology of migraine and its possible chronicity are not fully understood, previous studies have shown in patients with migraine molecular alterations of systemic inflammation, neurogenic inflammation, endothelial dysfunction, innate immunity, dysfunction of matrix proteases and blood-brain barrier. Periodontal disease is an inflammatory lesion caused by bacteria. After the bacterial infection begins, an immune response that will be responsible for individual susceptibility appears. More advanced forms of periodontitis have demonstrated molecular alterations of inflammation, endothelial dysfunction, dysfunction of matrix proteases and innate immunity, similar to those observed in migraine. Furthermore, the main molecular mediators of neurogenic inflammation related to activation of the trigeminovascular system, which are characteristic of migraine, are overexpressed in gingival crevicular fluid and mucosa in patients with periodontal disease. Hypertension, hypercholesterolemia, insulin resistance, stroke or coronary artery disease are comorbidities that periodontal disease and migraine could share. Therefore, several mechanisms and hypotheses could explain the possible association between both diseases. However, epidemiological and molecular studies will be necessary to provide a better understanding of this potential association, which could be implicated in the chronification of migraine.