Interictal amylin levels in chronic migraine patients: A case-control study

Abstract

Background Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine. Methods We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay. Results We assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 ± 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 ± 11.93, 95% female), and on 68 healthy controls (mean age 43.58 ± 11.08 years, 86% female). Body mass index was 25.94 ± 4.53 kg/m2 for migraine patients and 25.13 ± 4.92 kg/m2 for healthy controls ( p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p < 0.0001) and healthy controls (24.74 pg/mL, p < 0.0001). Plasma calcitonin gene-related peptide levels were increased (20.01 pg/mL) in chronic migraine patients when compared to healthy controls (11.37 pg/mL, p = 0.0016), but not to episodic migraine patients (18.89 pg/mL, p = 0.4369). Applying a cut-off concentration of 39.68 pg/mL plasma amylin, the sensitivity to differentiate chronic migraine from healthy controls was 57.6% and the specificity was 88.2%. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of aura did not influence the plasma concentrations of amylin or calcitonin gene-related peptide. Conclusion Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a diagnostic biomarker for chronic migraine.

Beyond CGRP: The calcitonin peptide family as targets for migraine and pain

“…CGRP concentrations are reportedly elevated in the plasma, synovial fluid and CSF across a range of painful conditions: from tumourassociated pain to chronic lower back pain (Schou et al, 2017). This is consistent with migraine patients, where elevated plasma CGRP-LI has been observed during acute migraine attacks and in chronic migraine patients compared with healthy controls (Goadsby et al, 1990;Irimia et al, 2020). Interestingly, this elevation has been reported for up to 3 days following an acute migraine attack, suggesting sustained CGRP transcription and synthesis and/or release (Durham, 2006).…”

“…Although the role of amylin in pain disorders is not well understood, studies examining amylin in primary headache disorders suggest a potential pro-nociceptive role for this peptide. In patients suffering from chronic, and to a lesser extent episodic, migraine displayed an elevated concentration of circulating amylin-LI, measured by ELISA, relative to non-migraineurs (Irimia et al, 2020). This elevation was independent of an individual's metabolic status and obesity.…”

Amylin Analog Pramlintide Induces Migraine‐like Attacks in Patients

“…The most likely mechanisms are through activation of amylin‐responsive receptors in the peripheral sensory neurons, 40 the circumventricular organs, or within the brain, although the amounts of amylin that cross the blood–brain barrier are very small 41–43 . A recent study reported that amylin levels were higher in chronic migraine patients compared to episodic migraine patients 44 . At present, it is unknown whether plasma amylin is increased during spontaneous migraine attacks.…”

Cutaneous Allodynia in Migraine: A Narrative Review

“…In the periphery, the nociceptive fibers from TG neurons innervate the meninges, dural blood vessels, middle meningeal artery, and large cerebral arteries. Activation and sensitization of these peripheral structures occurs by the local release of vasoactive peptides, such as calcitonin gene-related peptide (CGRP), amylin, substance P and pituitary adenylate cyclase-activating peptide (PACAP) (49)(50)(51)(52), and inflammatory mediators (49). Sensitization of peripheral afferent TG fibers, or peripheral sensitization, explains the characteristic throbbing pain that worsens with physical activity during migraine attacks (49).…”