Migraine & Headache
Migraine affects one in seven people worldwide and is characterized by recurrent, intense headaches often accompanied by nausea, visual disturbances, and sensitivity to light or sound. Migraine is a neurovascular disorder driven by trigeminovascular activation and sensitization rather than classical peripheral nerve injury, requiring dedicated translational models distinct from other neuropathic pain states. Transpharmation offers validated migraine-relevant paradigms based on nitroglycerin (GTN), PACAP-38, and CGRP administration, each triggering cephalic and extracephalic hypersensitivity consistent with clinically validated migraine mechanisms and used extensively to evaluate CGRP-pathway and triptan-class therapeutics.
Models
Migraine is a highly prevalent and disabling condition, and intravenous glyceryl trinitrate (GTN), a nitric oxide (NO) donor, is a well-established human provocation model, reliably triggering migraine-like headache in susceptible individuals. In rats, GTN induces periorbital and hindpaw mechanical allodynia, assessed by von Frey filaments, alongside spontaneous pain-like behaviors — a phenotype considered the extracephalic and craniofacial correlate of migraine-associated allodynia reported by patients. The model’s specificity and translational validity are confirmed by its responsiveness to sumatriptan, the prototypic anti-migraine therapeutic, which attenuates both the behavioral and neuronal (c-Fos) hallmarks of GTN-induced activation.
Pituitary adenylate-cyclase-activating polypeptide-38 (PACAP-38) is a neuropeptide with strong clinical validity as a migraine trigger: intravenous infusion provokes delayed migraine-like attacks in the majority of migraine patients, with sumatriptan able to abort the response. In rats, subcutaneous administration of PACAP-38 reproduces this phenotype, inducing mechanical allodynia (periorbital and hindpaw, assessed by von Frey), light aversion, and other migraine-like behaviors. PACAP-induced hypersensitivity persists despite pharmacological or genetic blockade of CGRP signaling, indicating a pathway that is largely independent of — and complementary to — the CGRP axis.
Read the full description: Pituitary adenylate-cyclase-activating polypeptide-38 (PACAP-38)
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Humanized Models PXB humanized-liver mice
SPIDAR Rapid analgesic screening
Transgenics Genetically modified mice
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