Journal: Frontiers in Cell and Developmental Biology

Article Title: CGRP-mediated neuro-vascular-pulp cell crosstalk is essential for dental pulp repair

doi: 10.3389/fcell.2026.1793692

Figure Lengend Snippet: CGRP Promotes Angiogenesis in HUVECs and Pulp Repair via Upregulation of CD31/VEGFA (A) Representative images of tube formation assays using HUVECs treated with or without CGRP. Scale bar, 500 µm. (n = 3, *p < 0.05, **p < 0.01 vs. NC group). (B) ​ Representative images of scratch wound healing assays of HUVECs at 0,12 and 24 h post-CGRP treatment and quantitative analysis of wound closure rate. Scale bar, 100 µm. (n = 3, *p < 0.05 vs. NC group). (C) ​ qRT-PCR and Western blot analysis of CD31 and VEGFA levels in HUVECs. (n = 3, **p < 0.01, ***p < 0.001 vs. NC group). (D) ​ Representative immunofluorescence images showing CD31 + blood vessels (red) in the injured pulp region of mice treated with either vehicle (NC) or the CGRP receptor antagonist BIBN4096BS. Nuclei are counterstained with DAPI (blue). Scale bar, 50 µm. Green dashed line, dentin injury (cavity). Green arrow, region of interest (ROI) in the pulp horn beneath the injury site, where vascular changes were analyzed. (E) ​ CGRP-activated endothelial cells promote the mineralization of DPSCs via a paracrine mechanism. (n = 3, **p < 0.01vs. NC group).

Article Snippet: The CGRP receptor antagonist BIBN4096BS was purchased from Shanghai Haoyuan Chemexpress Co. (Shanghai, China).

Techniques: Quantitative RT-PCR, Western Blot, Immunofluorescence

Journal: Frontiers in Pharmacology

Article Title: Gepants: targeting the CGRP pathway for migraine relief

doi: 10.3389/fphar.2025.1708226

Figure Lengend Snippet: Trigeminovascular system and pathways of migraine pain transmission (created by BioRender; based on ( ; )). Activation of the trigeminovascular system plays a central role in the pathophysiology of migraine. The headache phase begins with activation of meningeal nociceptive afferents: unmyelinated C fibers and thinly myelinated Aδ fibers arising mainly from the ophthalmic (V1) but also from the maxillary (V2) and mandibular (V3) divisions of the trigeminal nerve. These fibers densely innervate meningeal blood vessels and, upon activation, release vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, nitric oxide (NO), and neurokinin A. These mediators promote vasodilation, neurogenic inflammation, and peripheral sensitization. Nociceptive signals from trigeminal ganglion (TG) neurons are transmitted via the trigeminocervical complex (TCC) to higher brain centers, including the thalamus, hypothalamus, and cortical regions such as the somatosensory cortex (S1/S2), motor cortex (M1/M2), visual cortex (VC), insula (IN), parietal association cortex (PA), and auditory cortex (AU). Brainstem nuclei, including the locus coeruleus (LC), periaqueductal gray (PAG), parabrachial nucleus (PB), and superior salivatory nucleus (SSN), further modulate pain transmission, underscoring the complexity of the neural networks underlying migraine pathogenesis.

Article Snippet: In 2004, Boehringer Ingelheim reported the first clinical data on CGRP receptor antagonists, introducing the small-molecule class now known as gepants ( ).

Techniques: Transmission Assay, Activation Assay

Journal: Frontiers in Pharmacology

Article Title: Gepants: targeting the CGRP pathway for migraine relief

doi: 10.3389/fphar.2025.1708226

Figure Lengend Snippet: Mechanism of action of gepants in migraine therapy (created by BioRender, based on ). Schematic representation of calcitonin gene–related peptide (CGRP) release from trigeminal nerve terminals in response to potential migraine triggers (e.g., stress, hormonal changes, light, smell, alcohol, weather). Upon release, CGRP binds to its receptor, a heterotrimeric complex consisting of the calcitonin receptor-like receptor (CLR), receptor activity–modifying protein 1 (RAMP1), and receptor component protein (RCP), which activates intracellular Gs-protein–mediated signaling. Gepants are small-molecule antagonists that block CGRP binding at its receptor, thereby preventing the transmission of nociceptive information and attenuating migraine pathophysiology.

Article Snippet: In 2004, Boehringer Ingelheim reported the first clinical data on CGRP receptor antagonists, introducing the small-molecule class now known as gepants ( ).

Techniques: Activity Assay, Blocking Assay, Binding Assay, Transmission Assay

Journal: Frontiers in Pharmacology

Article Title: Gepants: targeting the CGRP pathway for migraine relief

doi: 10.3389/fphar.2025.1708226

Figure Lengend Snippet: Chemical structures of clinically approved gepants (created by BioRender; based on ( ; ; ; )). Representative small-molecule CGRP receptor antagonists currently approved for clinical use include atogepant, ubrogepant, rimegepant, and zavegepant. Despite structural diversity, these molecules share the ability to selectively block the CGRP receptor, thereby preventing receptor activation and downstream signaling in the trigeminovascular system. Structural modifications between successive generations have improved oral bioavailability, metabolic stability, and safety, reducing hepatotoxicity observed with earlier compounds.

Article Snippet: In 2004, Boehringer Ingelheim reported the first clinical data on CGRP receptor antagonists, introducing the small-molecule class now known as gepants ( ).

Techniques: Blocking Assay, Activation Assay