AUTHOR=Bründl Elisabeth , Proescholdt Martin , Störr Eva-Maria , Schödel Petra , Bele Sylvia , Zeman Florian , Hohenberger Christoph , Kieninger Martin , Schmidt Nils Ole , Schebesch Karl-Michael 

TITLE=The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage–A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.889213

DOI=10.3389/fneur.2022.889213

ISSN=1664-2295

ABSTRACT=<sec><title>Background</title><p>The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL.</p></sec><sec><title>Methods</title><p>Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out <italic>n</italic> = 5): <italic>n</italic> = 9 underwent endovascular aneurysm occlusion, <italic>n</italic> = 6 microsurgery, and <italic>n</italic> = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t<sub>1</sub>: day 11–35) and at the FU (t<sub>2</sub>).</p></sec><sec><title>Results</title><p>During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; <italic>p</italic> = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (<italic>p</italic> = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (<italic>p</italic> = 0.010) and compared to the first 10 days (<italic>p</italic> = 0.026). Higher mean serum CGRP levels at 3 weeks (<italic>p</italic> = 0.001) and at 6 months (<italic>p</italic> = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (<italic>p</italic> = 0.001) at t<sub>2</sub>.</p></sec><sec><title>Conclusion</title><p>Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing.</p></sec>