Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin

Zarban, Ali A.; Chaudhry, Hiba; Valente, João de Sousa; Argunhan, Fulye; Ghanim, Hala; Brain, Susan D.

doi:10.3390/ijms232012246

Cited by 4 publications

(3 citation statements)

References 66 publications

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“…Calcitonin gene-related peptide (CGRP) is a potent, vasodilated neuropeptide involved in migraine pathophysiology. 1 CGRP antagonists and monoclonal antibodies (mAbs) targeting CGRP have been associated with aborting and preventing migraine attacks. 2,3 CGRP has also been found in pulmonary afferent nerve fibers and may play a role in broncho-protection and immunomodulation.…”

Section: Introductionmentioning

confidence: 99%

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Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Wang

Fenton

Deng³

et al. 2023

JAMA Netw Open

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ImportanceCalcitonin gene–related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19.ObjectiveTo evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death.Design, Setting, and ParticipantsThis retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022.ExposureInitiation of CGRP mAbs.Main Outcomes and MeasuresThe main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes.ResultsAmong 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability–weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2.Conclusions and RelevanceIn this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.

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Section: Introductionmentioning

confidence: 99%

“…Calcitonin gene–related peptide (CGRP) is a potent, vasodilated neuropeptide involved in migraine pathophysiology . CGRP antagonists and monoclonal antibodies (mAbs) targeting CGRP have been associated with aborting and preventing migraine attacks .…”

Section: Introductionmentioning

confidence: 99%

Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Wang

Fenton

Deng³

et al. 2023

JAMA Netw Open

View full text Add to dashboard Cite

show abstract

“…Proinflammatory neuropeptides, including CGRP, are released from the activated sensory nerve endings, leading to the vasodilation, plasma protein extravasation, oedema formation, and leukocyte accumulation involved in both acute and chronic inflammatory processes. The vasodilator activity of the CGRP-potentiating substance P-and tumor necrosis factor-α alpha-induced oedema and neutrophil accumulation was characterized in the skin microvasculature of mice [11]. Similar to CGRP, PACAP is also pro-inflammatory on the vascular components by inducing strong vasodilation but anti-inflammatory on the cellular components, which makes its overall role in migraine unclear.…”

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confidence: 99%

Molecular Links between Sensory Nerves, Inflammation, and Pain 2.0

Szőke,

Helyes

2023

IJMS

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Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis

Leech,

Peiris

2024

J Gastroenterol

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Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD is proton pump inhibitors (PPIs), however, PPIs are ineffective in a large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number and location are likely to play interrelated roles in nociception in the oesophagus of GORD patients. Simultaneously, alterations in cells of the oesophageal mucosa, namely epithelial cells, mast cells, dendritic cells, and T lymphocytes, have been a focus of GORD research for several years. The oesophagus of GORD patients exhibits both macro- and micro-inflammation as a response to chronic acidic reflux at the epithelium. In other conditions of the GI tract, such as IBS and IBD, well-characterised bidirectional processes between immune cells and mucosal nerve fibres contribute to pathogenesis and symptom generation. Sensory alterations in these conditions such as nerve fibre outgrowth and hypersensitivity can be driven by inflammatory processes, which promote visceral pain signalling. This review will examine what is currently known of the molecular pathways linking inflammation and sensory perception leading to the development of GORD symptoms and explore potentially relevant mechanisms in other GI regions which may indicate new areas in GORD research.

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Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin

Cited by 4 publications

References 66 publications

Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Molecular Links between Sensory Nerves, Inflammation, and Pain 2.0

Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis

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