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Article Open Access

Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1β levels in patients with periodontitis suffering from migraines

  • Authors:
    • Sudheer Krishna Gonthupuli
    • Deepa Ponnaiyan
    • Chandrasekar Mani Anitha
    • Ponnudurai Samuel Gnana Prakash
    • Dhayanand John Victor
    • Neeraj Verma
  • View Affiliations / Copyright

    Affiliations: Department of Periodontics, SRM Dental College Ramapuram, Chennai, Tamil Nadu 600089, India
    Copyright: © Gonthupuli et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 23
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    Published online on: February 11, 2026
       https://doi.org/10.3892/wasj.2026.438
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Abstract

Periodontitis is characterized by dysregulated host immune responses to Gram‑negative anaerobes, resulting in local tissue destruction and systemic inflammatory spill‑over. In parallel, neurovascular inflammation potentially influenced by mediators, such as interleukin‑1β (IL‑1β), calcitonin gene‑related peptide (CGRP) and pentraxin‑3 (PTX‑3) is associated with migraine chronification. Given the biological overlap between mucosal and systemic inflammatory pathways, the present study assessed serum and salivary IL‑1β, CGRP and PTX‑3 levels in 96 individuals allocated to four groups as follows: Healthy controls, patients with chronic migraines without periodontitis, periodontitis without migraines, and patients with chronic migraines with periodontitis. Biomarker levels were quantified using validated ELISA protocols, and the periodontal status was evaluated using the plaque index, modified sulcular bleeding index, probing depth and clinical attachment level. Individuals with co‑existing chronic migraines and periodontitis exhibited the highest salivary and serum biomarker concentrations. The salivary IL‑1β level was consistently higher than the serum levels, whereas CGRP and PTX‑3 levels were predominantly elevated in serum. Significant correlations were observed between the salivary and serum concentrations of all markers, and between biomarker levels and periodontal parameters. These findings indicate an amplified inflammatory burden in individuals with both conditions and support the concept of a shared neurovascular‑immune axis. Although the cross‑sectional design precludes causal inference, the results of the present study highlight the potential relevance of periodontal status in the inflammatory profile of chronic migraine.
View Figures

Figure 1

Migraine screening questionnaire:
This consists of all five questions which were used in the present
study to assess frequency, intensity, duration, associated
symptoms, sensitivity to light or noise and limitation of physical
activities during the attack.

Figure 2

Absorbance at 414 nm for saliva
samples: Three clean saliva samples show very low absorbance values
(0.003-0.005 AU), well below the predefined contamination threshold
of 0.06 AU. The contaminated reference sample displays a marked
absorbance peak (0.083 AU), illustrating the sensitivity of the
hemoglobin screening procedure.

Figure 3

Scatter plots illustrating
correlations between salivary biomarkers. (A-I) Pairwise
associations among salivary IL-1β, CGRP and PTX-3 levels. Each
panel displays individual data points with a fitted linear
regression line; all correlations were statistically significant
(P<0.001). CAL, clinical attachment level; PI, plaque index;
CGRP, calcitonin gene-related peptide; PTX-3, pentraxin-3; IL-1β,
interleukin 1β.

Figure 4

Scatter plots illustrating
correlations between serum biomarkers. (A-I) Pairwise associations
among serum IL-1β, CGRP and PTX-3 concentrations. Individual
observations and linear regression lines are shown in each panel;
all correlations were statistically significant (P<0.001). CAL,
clinical attachment level; PI, plaque index; CGRP, calcitonin
gene-related peptide; PTX-3, pentraxin-3; IL-1β, interleukin
1β.

Figure 5

Scatter plots illustrating
correlations between salivary and serum biomarker levels. (A-I)
Pairwise correlations between salivary and serum IL-1β, CGRP and
PTX-3. Each panel includes individual data points, a linear
regression line, and Pearson's correlation coefficients (r). All
correlations were statistically significant (P<0.001). CGRP,
calcitonin gene-related peptide; PTX-3, pentraxin-3; IL-1β,
interleukin 1β.

Figure 6

Correlation analysis scatter plots of
saliva CGRP, PTX-3 and IL-1β levels in relation to probing pocket
depth and clinical attachment level. (A) Saliva CGRP levels
correlated with probing pocket depth. (B) Saliva PTX-3 levels
correlated with probing pocket depth. (C) saliva IL-1β correlated
with probing pocket depth. (D) Saliva CGRP levels correlated with
clinical attachment level. (E) Saliva PTX-3 levels correlated with
clinical attachment level. (F) Saliva IL-1β correlated with
clinical attachment level. Linear regression lines with 95%
confidence interval bands are displayed for each subplot. All
correlations were statistically significant (P<0.001). CGRP,
calcitonin gene-related peptide; PTX-3, pentraxin-3; IL-1β,
interleukin 1β.

Figure 7

Correlation analysis scatter plots of
serum CGRP, PTX-3 and IL-1β levels in relation to probing pocket
depth and clinical attachment level. (A) Serum CGRP levels
correlated with probing pocket depth. (B) Serum PTX-3 levels
correlated with probing pocket depth. (C) Serum IL-1β correlated
with probing pocket depth. (D) Serum CGRP levels correlated with
clinical attachment level. (E) Serum PTX-3 levels correlated with
clinical attachment level. (F) Serum IL-1β correlated with clinical
attachment level. Linear regression lines with 95% confidence
interval bands are displayed for each subplot. All correlations
were statistically significant (P<0.001). CGRP, calcitonin
gene-related peptide; PTX-3, pentraxin-3; IL-1β, interleukin
1β.
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Copy and paste a formatted citation
Spandidos Publications style
Gonthupuli SK, Ponnaiyan D, Anitha CM, Prakash PS, Victor DJ and Verma N: Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines. World Acad Sci J 8: 23, 2026.
APA
Gonthupuli, S.K., Ponnaiyan, D., Anitha, C.M., Prakash, P.S., Victor, D.J., & Verma, N. (2026). Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines. World Academy of Sciences Journal, 8, 23. https://doi.org/10.3892/wasj.2026.438
MLA
Gonthupuli, S. K., Ponnaiyan, D., Anitha, C. M., Prakash, P. S., Victor, D. J., Verma, N."Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines". World Academy of Sciences Journal 8.2 (2026): 23.
Chicago
Gonthupuli, S. K., Ponnaiyan, D., Anitha, C. M., Prakash, P. S., Victor, D. J., Verma, N."Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines". World Academy of Sciences Journal 8, no. 2 (2026): 23. https://doi.org/10.3892/wasj.2026.438
Copy and paste a formatted citation
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Spandidos Publications style
Gonthupuli SK, Ponnaiyan D, Anitha CM, Prakash PS, Victor DJ and Verma N: Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines. World Acad Sci J 8: 23, 2026.
APA
Gonthupuli, S.K., Ponnaiyan, D., Anitha, C.M., Prakash, P.S., Victor, D.J., & Verma, N. (2026). Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines. World Academy of Sciences Journal, 8, 23. https://doi.org/10.3892/wasj.2026.438
MLA
Gonthupuli, S. K., Ponnaiyan, D., Anitha, C. M., Prakash, P. S., Victor, D. J., Verma, N."Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines". World Academy of Sciences Journal 8.2 (2026): 23.
Chicago
Gonthupuli, S. K., Ponnaiyan, D., Anitha, C. M., Prakash, P. S., Victor, D. J., Verma, N."Serum and salivary calcitonin gene‑related peptide, pentraxin‑3 and interleukin‑1&beta; levels in patients with periodontitis suffering from migraines". World Academy of Sciences Journal 8, no. 2 (2026): 23. https://doi.org/10.3892/wasj.2026.438
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