# Pathophysiology of Occipital Migraine

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $382,813

## Abstract

Project Summary. Occipital headaches can be migrainous or non-migraineous. When migrainous, they are
often preceded or accompanied by dizziness, vertigo, decreased motor coordination, instability, insecure
walking, clumsiness, and reduced coordination – all of which could be attributed (at least partially) to cerebellar
dysfunction – and muscle tenderness that is aggravated by neck motion. These 2 scenarios suggest that
occipital headache can be triggered intracranially, by transient episodes of abnormal cerebellar functioning,
and/or extracranially, by acute episodes of neck muscles ache. Given that more than 2/3 of all migraine
patients experience muscle tenderness that radiates to the back of the head, it is surprising how little is known
about the functional properties of the central neurons that process nociceptive information from the dura
overlying the cerebellum, and even more so, how little is known about the mechanisms by which headaches
that originate intracranially affect sensory processing of muscles and, vice versa, how tenderness of neck
muscles affects processing of sensory signals from the posterior dura. The broad objective of this proposal is
to define the neural substrate of occipital headaches. Our working hypothesis is that occipital headaches could
be initiated intracranially by cerebellar spreading depression (CbSD) and extracranially by acute muscle pain –
each one involving different patterns of activation and sensitization of C2-4 dorsal horn neurons that innervate
posterior dura and neck muscles, and whose axons establish reciprocal connections with brainstem and
hypothalamic nuclei that (a) generate some of the classical symptoms of migraine and (b) modulate the firing
of these same neurons. This working hypothesis will be tested in 3 aims: 1) determine whether CbSD is
capable of activating and/or sensitizing C2-4 dorsal horn neurons that receive convergent signals from the
occipital dura and neck muscles; 2) determine whether induction of muscle pain can sensitize these neurons to
the extent that it affects how they process sensory signals that originate in the cerebellar dura; and 3) map the
axonal course and projection targets of these neurons, and determine whether they receive input from
hypothalamic (i.e. orexin, oxytocin), brainstem (i.e., 5HT) and sensory ganglia (i.e. CGRP) neurons thought to
play a role in migraine pathophysiology. Clinically, the proposed animal studies have the potential to shed new
light on how occipital headaches that begin in pericranial tissues differ from occipital headaches that begin
intracranially. Therapeutically, the findings may expand our understanding of cervical manipulations commonly
used in the treatment of migraine and non-migraine headaches; from assuming that it is mediated by reduction
of nociceptive signals travelling along the occipital nerve to include reduction of nociceptive signals that
originate in the posterior dura. Scientifically, the potential to identify nov...

## Key facts

- **NIH application ID:** 10297828
- **Project number:** 5R01NS104296-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Rodrigo Noseda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,813
- **Award type:** 5
- **Project period:** 2017-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297828

## Citation

> US National Institutes of Health, RePORTER application 10297828, Pathophysiology of Occipital Migraine (5R01NS104296-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10297828. Licensed CC0.

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