Headache Disorder Organoid Modeling Service

Migraine and other primary headache disorders represent intricate neurological ailments whose complex pathophysiology continues to elude a complete mechanistic understanding. The limitations of animal models in recapitulating the sensory and affective experience of a migraine attack have slowed the development of novel, mechanism-based therapies. A critical need exists for human-specific models that can dissect the intricate interplay between genetic predispositions, environmental triggers, and the complex neural circuits that drive headache pathogenesis.

To address this critical research gap, Creative Biolabs introduces an advanced Headache Disorder Organoid Modeling Service. We construct high-fidelity 3D models of the key neural pathways implicated in migraine and other headache disorders.

Reconstructing the Trigeminovascular System & Central Pain Pathways

We have developed a unique portfolio of region-specific organoids and assembloids designed to model the critical nodes of the pain-processing network, from the periphery to the cortex.

1. Trigeminal Ganglia (TG) Organoids: The initiation of headache pain begins with the activation of the trigeminovascular system. Our iPSC-derived TG organoids contain functional sensory nociceptors, allowing for the direct study of peripheral sensitization and the mechanisms of neuropeptide release (e.g., CGRP).
2. Brainstem Assembloids: To model central pain modulation, we construct assembloids that fuse organoids representing key brainstem nuclei. This includes models of the trigeminal cervical complex (TCC), where primary afferents synapse, and the periaqueductal gray (PAG), which controls descending pain modulation. These platforms are ideal for studying the mechanisms of central sensitization.
3. Thalamocortical & Hypothalamic Organoids: We model the higher-order processing of pain and associated symptoms using region-specific organoids. Our thalamic organoid models provide a unique platform to dissect the sensory-discriminative pathways of pain and to explore the cellular mechanisms underlying key symptoms such as allodynia, photophobia, and phonophobia. Hypothalamic organoids allow for the study of premonitory symptoms and the role of the hypothalamus in triggering migraine attacks.
4. Cortical Organoids for Modeling Aura: For migraine with aura, we utilize cortical organoids to create a platform for investigating the cellular basis of Cortical Spreading Depression (CSD), including neuronal and glial responses to waves of depolarization.

A Versatile Platform for Migraine & Headache Research

Our organoid models provide actionable data to address the most pressing questions in headache research.

1. Elucidating Disease Mechanisms: Probe the molecular basis of key pathological events such as Cortical Spreading Depression (CSD), central sensitization, and neurogenic neuroinflammation in a human-relevant cellular system.
2. Modeling Genetic Channelopathies: Using patient-derived iPSCs (e.g., from individuals with Familial Hemiplegic Migraine), we model the functional impact of specific ion channel mutations (CACNA1A, ATP1A2, SCN1A) on neuronal excitability.
3. High-Throughput Therapeutic Screening: Our platforms are ideal for testing the efficacy and mechanism of action of novel therapeutics, including small molecules, biologics, and agents targeting the CGRP pathway or other neuropeptides.
4. Analysis of Migraine Triggers: Apply chemical, inflammatory, or other environmental stressors to the models to investigate the cellular pathways that initiate a migraine attack.

Our Workflow

Move Beyond the Limits of Conventional Models. Illuminate the Mechanisms of Migraine.

Leverage the power of human-specific brain organoids to accelerate your headache and pain research.

Speak with a Pain Modeling Specialist

Reference

1. Gazerani, Parisa. "Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development." International journal of molecular sciences vol. 24,4 3113. 4 Feb. 2023, doi:10.3390/ijms24043113. Distributed under Open Access License CC BY 4.0 without modification.